Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development

American Journal of Obstetrics and Gynecology

Volumn 215, Issue 1, 2016, Pages S1-S46

  Ilekis, John V ^a   Tsilou, Ekaterini ^a   Fisher, Susan ^b   Abrahams, Vikki M ^c   Soares, Michael J ^e   Cross, James C ^d   Zamudio, Stacy ^f   Illsley, Nicholas P ^f   Myatt, Leslie ^g   Colvis, Christine ^h   Costantine, Maged M ⁱ   Haas, David M ^j   Sadovsky, Yoel ^k   Weiner, Carl ^l   Rytting, Erik ⁱ   Bidwell, Gene ^m  

^a EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d Health Sciences Centre Calgary   (Canada)

^e UNIVERSITY OF KANSAS SCHOOL OF MEDICINE   (United States)

^f HACKENSACK UNIVERSITY MEDICAL CENTER   (United States)

^g UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

^h NATIONAL INSTITUTES OF HEALTH   (United States)

ⁱ University of Texas Medical Branch School of Medicine   (United States)

^j INDIANA UNIVERSITY   (United States)

^k UNIVERSITY OF PITTSBURGH   (United States)

^l UNIVERSITY OF KANSAS MEDICAL CENTER   (United States)

^m UNIVERSITY OF MISSISSIPPI SCHOOL OF MEDICINE   (United States)

more..

Author keywords

drugs; placenta; pregnancy; therapeutics; trial

Indexed keywords

ALLOPURINOL; AMPICILLIN; ARGININE; BIOPOLYMER; CARBAMAZEPINE; CEFAZOLIN; CEFUROXIME; DIGOXIN; FEBUXOSTAT; INDINAVIR; LITHIUM; LOPINAVIR; MESSENGER RNA; METFORMIN; MICRORNA; MIDAZOLAM; NANOPARTICLE; NIFEDIPINE; OXYGEN; PATTERN RECOGNITION RECEPTOR; PIPERACILLIN; PRAVASTATIN; RECOMBINANT VASCULOTROPIN; RITONAVIR; RNA; SAQUINAVIR; SILDENAFIL; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR 8; TRANSCRIPTOME; BIOLOGICAL MARKER; GENETIC MARKER;

BACTERIUM; CELL DIFFERENTIATION; CELL FREE SYSTEM; CELL INVASION; CELL MIGRATION; CHICKEN; CLINICAL RESEARCH; CONFERENCE PAPER; CYTOTROPHOBLAST; DRUG ABSORPTION; DRUG DELIVERY SYSTEM; DRUG SAFETY; DRUG TARGETING; EUROPE; FETUS GROWTH; GENE THERAPY; HUMAN; HYPOXIA; INTRAUTERINE GROWTH RETARDATION; METRITIS; MULTICENTER STUDY (TOPIC); NATIONAL HEALTH ORGANIZATION; NATURAL KILLER CELL; NITROSATIVE STRESS; NONHUMAN; OXIDATIVE STRESS; OXYGEN THERAPY; PHARMACODYNAMICS; PHARMACOKINETIC PARAMETERS; PLACENTA; PLACENTA CIRCULATION; PLACENTA DEVELOPMENT; PLACENTA DISORDER; PLACENTA FUNCTION; PLACENTA HYPOXIA; PREECLAMPSIA; PREGNANCY DISORDER; PREGNANCY OUTCOME; PREGNANT WOMAN; PRENATAL DRUG EXPOSURE; PRIORITY JOURNAL; REPRODUCTION; TRANSLATIONAL RESEARCH; TROPHOBLAST; UNITED STATES; VULNERABLE POPULATION; WORKSHOP; ANIMAL; ANIMAL MODEL; DRUG DEVELOPMENT; EMBRYOLOGY; FEMALE; GENETIC MARKER; GENETICS; IMMUNOLOGY; METABOLISM; MOLECULARLY TARGETED THERAPY; MOUSE; PATHOPHYSIOLOGY; PLACENTA DISEASES; PREGNANCY; RAT;

ANIMALS; BIOMARKERS; DRUG DELIVERY SYSTEMS; DRUG DISCOVERY; FEMALE; GENETIC MARKERS; HUMANS; MICE; MODELS, ANIMAL; MOLECULAR TARGETED THERAPY; NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT (U.S.); PLACENTA; PLACENTA DISEASES; PREGNANCY; PREGNANCY OUTCOME; RATS; TRANSLATIONAL MEDICAL RESEARCH; UNITED STATES;

EID: 85002068845     PISSN: 00029378     EISSN: 10976868     Source Type: Journal    
DOI: 10.1016/j.ajog.2016.03.001     Document Type: Conference Paper

References (484)

1. Chaddha, V., Viero, S., Huppertz, B., Kingdom, J., Developmental biology of the placenta and the origins of placental insufficiency. Semin Fetal Neonatal Med 9 (2004), 357–369.
2. Fisher, S.J., The placental problem: linking abnormal cytotrophoblast differentiation to the maternal symptoms of preeclampsia. Reprod Biol Endocrinol, 2, 2004, 53.
3. Redline, R.W., Placental inflammation. Semin Neonatol 9 (2004), 265–274.
4. Andraweera, P.H., Dekker, G.A., Roberts, C.T., The vascular endothelial growth factor family in adverse pregnancy outcomes. Hum Reprod Update 18 (2012), 436–457.
5. Kingdom, J., Huppertz, B., Seaward, G., Kaufmann, P., Development of the placental villous tree and its consequences for fetal growth. Eur J Obstet Gynecol Reprod Biol 92 (2000), 35–43.
6. Jansson, T., Aye, I.L., Goberdhan, D.C., The emerging role of mTORC1 signaling in placental nutrient-sensing. Placenta 33:suppl 2 (2012), e23–e29.
7. Perkins, N.D., Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 8 (2007), 49–62.
8. Macintyre, D.A., Sykes, L., Teoh, T.G., Bennett, P.R., Prevention of preterm labour via the modulation of inflammatory pathways. J Matern Fetal Neonatal Med 25:suppl 1 (2012), 17–20.
9. The NCGC/NCATS Pharmaceutical Collection (vol 2015). Available at: http://tripod.nih.gov/npc. Accessed: June 3, 2015.
10. PubChem. Available at: http://pubchem.ncbi.nlm.nih.gov. Accessed: June 3, 2015.
11. The DrugBank database. Available at http://www.drugbank.ca. Accessed: June 3, 2015.
12. KEGG DRUG. Available at http://www.genome.jp/kegg/drug. Accessed: June 3, 2015.
13. GeneCards. Available at http://genecards.org. Accessed: June 3, 2015.
14. Toporkiewicz, M., Meissner, J., Matusewicz, L., Czogalla, A., Sikorski, A.F., Toward a magic or imaginary bullet? Ligands for drug targeting to cancer cells: principles, hopes, and challenges. Int J Nanomedicine 10 (2015), 1399–1414.
15. Silva, A.C., Lopes, C.M., Sousa Lobo, J.M., Amaral, M.H., Nucleic acids delivery systems: a challenge for pharmaceutical technologists. Curr Drug Metab 16 (2015), 3–16.
16. Burnett, J.C., Rossi, J.J., RNA-based therapeutics: current progress and future prospects. Chem Biol 19 (2012), 60–71.
17. Van Rooij, E., Kauppinen, S., Development of microRNA therapeutics is coming of age. EMBO Mol Med 6 (2014), 851–864.
18. Svenson, S., Prud'homme, R.E., Multifunctional nanoparticles for drug delivery applications: imaging, targeting, and delivery. 2012, Springer-Verlag, New York.
19. Vrachnis, N., Kalampokas, E., Sifakis, S., et al. Placental growth factor (PlGF): a key to optimizing fetal growth. J Matern Fetal Neonatal Med 26 (2013), 995–1002.
20. Maltepe, E., Bakardjiev, A.I., Fisher, S.J., The placenta: transcriptional, epigenetic, and physiological integration during development. J Clin Invest 120 (2010), 1016–1025.
21. Romero, R., Dey, S.K., Fisher, S.J., Preterm labor: one syndrome, many causes. Science 345 (2014), 760–765.
22. Redman, C.W., Preeclampsia: a multi-stress disorder. Rev Med Intern 32:suppl 1 (2011), S41–S44.
23. Brosens, I.A., Robertson, W.B., Dixon, H.G., The role of the spiral arteries in the pathogenesis of preeclampsia. J Pathol, 101, 1970 Pvi.
24. Brosens, I., Pijnenborg, R., Vercruysse, L., Romero, R., The “Great Obstetrical Syndromes” are associated with disorders of deep placentation. Am J Obstet Gynecol 204 (2011), 193–201.
25. Fisher, S.J., Why is placentation abnormal in preeclampsia?. Am J Obstet Gynecol 213:suppl (2015), S115–S122.
26. Zhou, Y., Damsky, C.H., Fisher, S.J., Preeclampsia is associated with failure of human cytotrophoblasts to mimic a vascular adhesion phenotype: one cause of defective endovascular invasion in this syndrome?. J Clin Invest 99 (1997), 2152–2164.
27. Zhou, Y., McMaster, M., Woo, K., et al. Vascular endothelial growth factor ligands and receptors that regulate human cytotrophoblast survival are dysregulated in severe preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome. Am J Pathol 160 (2002), 1405–1423.
28. Clark, D.E., Smith, S.K., He, Y., et al. A vascular endothelial growth factor antagonist is produced by the human placenta and released into the maternal circulation. Biol Reprod 59 (1998), 1540–1548.
29. Maynard, S.E., Min, J.Y., Merchan, J., et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 111 (2003), 649–658.
30. Venkatesha, S., Toporsian, M., Lam, C., et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med 12 (2006), 642–649.
31. Levine, R.J., Lam, C., Qian, C., et al. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med 355 (2006), 992–1005.
32. Hirashima, C., Ohkuchi, A., Takahashi, K., Suzuki, H., Matsubara, S., Suzuki, M., A novel three-step approach for predicting the imminent onset of preeclampsia within 4 weeks after blood sampling at 19-31 weeks of gestation. Hypertens Res 37 (2014), 519–525.
33. Chaiworapongsa, T., Romero, R., Whitten, A.E., et al. The use of angiogenic biomarkers in maternal blood to identify which SGA fetuses will require a preterm delivery and mothers who will develop pre-eclampsia. J Matern Fetal Neonatal Med, 2015, 1–15.
34. Nakimuli, A., Chazara, O., Hiby, S.E., et al. A KIR B centromeric region present in Africans but not Europeans protects pregnant women from pre-eclampsia. Proc Natl Acad Sci U S A 112 (2015), 845–850.
35. Zhou, Y., Gormley, M.J., Hunkapiller, N.M., et al. Reversal of gene dysregulation in cultured cytotrophoblasts reveals possible causes of preeclampsia. J Clin Invest 123 (2013), 2862–2872.
36. Berman, J., Girardi, G., Salmon, J.E., TNF-alpha is a critical effector and a target for therapy in antiphospholipid antibody-induced pregnancy loss. J Immunol 174 (2005), 485–490.
37. Lo, Y.M., Tein, M.S., Lau, T.K., et al. Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 62 (1998), 768–775.
38. Norton, M.E., Jacobsson, B., Swamy, G.K., et al. Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med 372 (2015), 1589–1597.
39. Koh, W., Pan, W., Gawad, C., et al. Noninvasive in vivo monitoring of tissue-specific global gene expression in humans. Proc Natl Acad Sci U S A 111 (2014), 7361–7366.
40. Redman, C.W., Sargent, I.L., Circulating microparticles in normal pregnancy and pre-eclampsia. Placenta 29:suppl A (2008), S73–S77.
41. Mincheva-Nilsson, L., Baranov, V., Placenta-derived exosomes and syncytiotrophoblast microparticles and their role in human reproduction: immune modulation for pregnancy success. Am J Reprod Immunol 72 (2014), 440–457.
42. Medzhitov, R., Recognition of microorganisms and activation of the immune response. Nature 449 (2007), 819–826.
43. Jin, C., Flavell, R.A., Innate sensors of pathogen and stress: linking inflammation to obesity. J Allergy Clin Immunol 132 (2013), 287–294.
44. Suman P, Gupta S. Immunology of Implantation, Implantation Failure and Pregnancy. Part A: Regulators of Early Invasion of Trophoblast Cells. In: Chaouat G, Olivier S, Ledee N, eds. Immunology of Pregnancy 2013: Bentham, 2013.
45. Kawai, T., Akira, S., The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11 (2010), 373–384.
46. Akira, S., Takeda, K., Toll-like receptor signalling. Nat Rev Immunol 4 (2004), 499–511.
47. Song, D.H., Lee, J.O., Sensing of microbial molecular patterns by Toll-like receptors. Immunol Rev 250 (2012), 216–229.
48. Kondo, T., Kawai, T., Akira, S., Dissecting negative regulation of Toll-like receptor signaling. Trends Immunol 33 (2012), 449–458.
49. O'Neill, L.A., When signaling pathways collide: positive and negative regulation of toll-like receptor signal transduction. Immunity 29 (2008), 12–20.
50. Shaw, M.H., Reimer, T., Kim, Y.G., Nunez, G., NOD-like receptors (NLRs): bona fide intracellular microbial sensors. Curr Opin Immunol 20 (2008), 377–382.
51. Franchi, L., Warner, N., Viani, K., Nunez, G., Function of Nod-like receptors in microbial recognition and host defense. Immunol Rev 227 (2009), 106–128.
52. Caruso, R., Warner, N., Inohara, N., Nunez, G., NOD1 and NOD2: signaling, host defense, and inflammatory disease. Immunity 41 (2014), 898–908.
53. Jin, C., Flavell, R.A., Molecular mechanism of NLRP3 inflammasome activation. J Clin Immunol 30 (2010), 628–631.
54. Martinon, F., Tschopp, J., Inflammatory caspases and inflammasomes: master switches of inflammation. Cell Death Differ 14 (2007), 10–22.
55. Cohen, P., The TLR and IL-1 signalling network at a glance. J Cell Sci 127 (2014), 2383–2390.
56. Nadeau-Vallee, M., Quiniou, C., Palacios, J., et al. Novel noncompetitive IL-1 receptor-biased ligand prevents infection- and inflammation-induced preterm birth. J Immunol 195 (2015), 3402–3415.
57. Netea, M.G., Simon, A., Van De Veerdonk, F., Kullberg, B.J., Van Der Meer, J.W., Joosten, L.A., IL-1beta processing in host defense: beyond the inflammasomes. PLoS Pathog, 6, 2010, e1000661.
58. Abrahams, V.M., Bole-Aldo, P., Kim, Y.M., et al. Divergent trophoblast responses to bacterial products mediated by TLRs. J Immunol 173 (2004), 4286–4296.
59. Abrahams, V.M., Visintin, I., Aldo, P.B., Guller, S., Romero, R., Mor, G., A role for TLRs in the regulation of immune cell migration by first trimester trophoblast cells. J Immunol 175 (2005), 8096–8104.
60. Costello, M.J., Joyce, S.K., Abrahams, V.M., NOD protein expression and function in first trimester trophoblast cells. Am J Reprod Immunol 57 (2007), 67–80.
61. Mulla, M.J., Yu, A.G., Cardenas, I., Guller, S., Panda, B., Abrahams, V.M., Regulation of Nod1 and Nod2 in first trimester trophoblast cells. Am J Reprod Immunol 61 (2009), 294–302.
62. Cardenas, I., Mulla, M.J., Myrtolli, K., et al. Nod1 activation by bacterial iE-DAP induces maternal-fetal inflammation and preterm labor. J Immunol 187 (2011), 980–986.
63. Ma, Y., Kadner, S.S., Guller, S., Differential effects of lipopolysaccharide and thrombin on interleukin-8 expression in syncytiotrophoblasts and endothelial cells: implications for fetal survival. Ann N Y Acad Sci 1034 (2004), 236–244.
64. Elovitz, M.A., Mrinalini, C., Animal models of preterm birth. Trends Endocrinol Metab 15 (2004), 479–487.
65. Wang, H., Hirsch, E., Bacterially-induced preterm labor and regulation of prostaglandin-metabolizing enzyme expression in mice: the role of toll-like receptor 4. Biol Reprod 69 (2003), 1957–1963.
66. Elovitz, M.A., Wang, Z., Chien, E.K., Rychlik, D.F., Phillippe, M., A new model for inflammation-induced preterm birth: the role of platelet-activating factor and Toll-like receptor-4. Am J Pathol 163 (2003), 2103–2111.
67. Cardenas, I., Means, R.E., Aldo, P., et al. Viral infection of the placenta leads to fetal inflammation and sensitization to bacterial products predisposing to preterm labor. J Immunol 185 (2010), 1248–1257.
68. Cardenas, I., Mor, G., Aldo, P., et al. Placental viral infection sensitizes to endotoxin-induced pre-term labor: a double hit hypothesis. Am J Reprod Immunol 65 (2011), 110–117.
69. Murphy, S.P., Fast, L.D., Hanna, N.N., Sharma, S., Uterine NK cells mediate inflammation-induced fetal demise in IL-10-null mice. J Immunol 175 (2005), 4084–4090.
70. Robertson, S.A., Skinner, R.J., Care, A.S., Essential role for IL-10 in resistance to lipopolysaccharide-induced preterm labor in mice. J Immunol 177 (2006), 4888–4896.
71. Aagaard, K., Ma, J., Antony, K.M., Ganu, R., Petrosino, J., Versalovic, J., The placenta harbors a unique microbiome. Sci Transl Med, 6, 2014, 237ra65.
72. Stout, M.J., Conlon, B., Landeau, M., et al. Identification of intracellular bacteria in the basal plate of the human placenta in term and preterm gestations. Am J Obstet Gynecol 208 (2013), 226.e1–226.e7.
73. Grigsby, P.L., Novy, M.J., Sadowsky, D.W., et al. Maternal azithromycin therapy for Ureaplasma intraamniotic infection delays preterm delivery and reduces fetal lung injury in a primate model. Am J Obstet Gynecol 207 (2012), 475.e1–475.e14.
74. Gravett, M.G., Adams, K.M., Sadowsky, D.W., et al. Immunomodulators plus antibiotics delay preterm delivery after experimental intraamniotic infection in a nonhuman primate model. Am J Obstet Gynecol 197 (2007), 518.e1–518.e8.
75. Ma, Y., Krikun, G., Abrahams, V.M., Mor, G., Guller, S., Cell type-specific expression and function of toll-like receptors 2 and 4 in human placenta: implications in fetal infection. Placenta 28 (2007), 1024–1031.
76. Abrahams, V.M., Aldo, P.B., Murphy, S.P., et al. TLR6 modulates first trimester trophoblast responses to peptidoglycan. J Immunol 180 (2008), 6035–6043.
77. Garg, M., Potter, J.A., Abrahams, V.M., Identification of microRNAs that regulate TLR2-mediated trophoblast apoptosis and inhibition of IL-6 mRNA. PLoS One, 8, 2013, e77249.
78. Mulla, M.J., Myrtolli, K., Tadesse, S., et al. Cutting-edge report: TLR10 plays a role in mediating bacterial peptidoglycan-induced trophoblast apoptosis. Am J Reprod Immunol 69 (2013), 449–453.
79. Ilievski, V., Lu, S.J., Hirsch, E., Activation of toll-like receptors 2 or 3 and preterm delivery in the mouse. Reprod Sci 14 (2007), 315–320.
80. Abrahams, V.M., Schaefer, T.M., Fahey, J.V., et al. Expression and secretion of antiviral factors by trophoblast cells following stimulation by the TLR-3 agonist, Poly(I: C). Hum Reprod 21 (2006), 2432–2439.
81. Aldo, P.B., Mulla, M.J., Romero, R., Mor, G., Abrahams, V.M., Viral ssRNA induces first trimester trophoblast apoptosis through an inflammatory mechanism. Am J Reprod Immunol 64 (2010), 27–37.
82. Potter, J.A., Garg, M., Girard, S., Abrahams, V.M., Viral single stranded RNA induces a trophoblast pro-inflammatory and antiviral response in a TLR8-dependent and -independent manner. Biol Reprod, 92, 2015, 17.
83. Koga, K., Cardenas, I., Aldo, P., et al. Activation of TLR3 in the trophoblast is associated with preterm delivery. Am J Reprod Immunol 61 (2009), 196–212.
84. Chatterjee, P., Weaver, L.E., Doersch, K.M., et al. Placental Toll-like receptor 3 and Toll-like receptor 7/8 activation contributes to preeclampsia in humans and mice. PLoS One, 7, 2012, e41884.
85. Van Beijnum, J.R., Buurman, W.A., Griffioen, A.W., Convergence and amplification of toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signaling pathways via high mobility group B1 (HMGB1). Angiogenesis 11 (2008), 91–99.
86. Romero, R., Chaiworapongsa, T., Alpay Savasan, Z., et al. Damage-associated molecular patterns (DAMPs) in preterm labor with intact membranes and preterm PROM: a study of the alarmin HMGB1. J Matern Fetal Neonatal Med 24 (2011), 1444–1455.
87. Bredeson, S., Papaconstantinou, J., Deford, J.H., et al. HMGB1 promotes a p38MAPK associated non-infectious inflammatory response pathway in human fetal membranes. PLoS One, 9, 2014, e113799.
88. Pradervand, P.A., Clerc, S., Frantz, J., et al. High mobility group box 1 protein (HMGB-1): a pathogenic role in preeclampsia?. Placenta 35 (2014), 784–786.
89. Girard, S. Jr., Guller, S., Sibley, C., Abraham, V., Alarmins potently induce inflammation in placental cells and impair trophoblast turnover. Reprod Sci, 22, 2015, 108A.
90. Meroni, P.L., Raschi, E., Grossi, C., et al. Obstetric and vascular APS: same autoantibodies but different diseases?. Lupus 21 (2012), 708–710.
91. Mulla, M.J., Yu, A.G., Cardenas, I., Guller, S., Panda, B., Abrahams, V.M., Regulation of Nod1 and Nod2 in first trimester trophoblast cells. Am J Reprod Immunol 61 (2009), 294–302.
92. Mulla, M.J., Salmon, J.E., Chamley, L.W., et al. A role for uric acid and the Nalp3 inflammasome in antiphospholipid antibody-induced IL-1beta production by human first trimester trophoblast. PLoS One, 8, 2013, e65237.
93. Mulla, M.J., Myrtolli, K., Potter, J., et al. Uric acid induces trophoblast IL-1beta production via the inflammasome: implications for the pathogenesis of preeclampsia. Am J Reprod Immunol 65 (2011), 542–548.
94. Gysler, S.M., MiR-146a Regulates Antiphospholipid Antibody-Induced IL-8 Secretion by Human Trophoblast Cells. Reprod Sci, 21, 2014, 116A.
95. Gysler, S.M., Mulla, M.J., Brosens, J.J., et al. Antiphospholipid antibody-induced miR-146a activates TLR8 in trophoblast and is inhibited by vitamin D. Reprod Sci, 22, 2015, 71A.
96. Han, C.S., Herrin, M.A., Pitruzzello, M.C., et al. Glucose and metformin modulate human first trimester trophoblast function: a model and potential therapy for diabetes-associated uteroplacental insufficiency. Am J Reprod Immunol 73 (2015), 362–371.
97. Koopmans, C.M., Van Pampus, M.G., Groen, H., Aarnoudse, J.G., Van Den Berg, P.P., Mol, B.W., Accuracy of serum uric acid as a predictive test for maternal complications in pre-eclampsia: bivariate meta-analysis and decision analysis. Eur J Obstet Gynecol Reprod Biol 146 (2009), 8–14.
98. Girard, S., Heazell, A.E., Derricott, H., et al. Circulating cytokines and alarmins associated with placental inflammation in high-risk pregnancies. Am J Reprod Immunol 72 (2014), 422–434.
99. Schmella, M.J., Clifton, R.G., Althouse, A.D., Roberts, J.M., Uric acid determination in gestational hypertension: is it as effective a delineator of risk as proteinuria in high-risk women?. Reprod Sci 22 (2015), 1212–1219.
100. Adams Waldorf, K.M., Persing, D., Novy, M.J., Sadowsky, D.W., Gravett, M.G., Pretreatment with toll-like receptor 4 antagonist inhibits lipopolysaccharide-induced preterm uterine contractility, cytokines, and prostaglandins in rhesus monkeys. Reprod Sci 15 (2008), 121–127.
101. Filipovich, Y., Lu, S.J., Akira, S., Hirsch, E., The adaptor protein MyD88 is essential for E coli-induced preterm delivery in mice. Am J Obstet Gynecol 200 (2009), 93.e1–93.e8.
102. Gotsch, F., Romero, R., Chaiworapongsa, T., et al. Evidence of the involvement of caspase-1 under physiologic and pathologic cellular stress during human pregnancy: a link between the inflammasome and parturition. J Matern Fetal Neonatal Med 21 (2008), 605–616.
103. Christiaens, I., Zaragoza, D.B., Guilbert, L., Robertson, S.A., Mitchell, B.F., Olson, D.M., Inflammatory processes in preterm and term parturition. J Reprod Immunol 79 (2008), 50–57.
104. Kemp, M.W., Saito, M., Newnham, J.P., Nitsos, I., Okamura, K., Kallapur, S.G., Preterm birth, infection, and inflammation advances from the study of animal models. Reprod Sci 17 (2010), 619–628.
105. Adams Waldorf, K.M., Rubens, C.E., Gravett, M.G., Use of nonhuman primate models to investigate mechanisms of infection-associated preterm birth. BJOG 118 (2011), 136–144.
106. Breen, K., Brown, A., Burd, I., Chai, J., Friedman, A., Elovitz, M.A., TLR-4–dependent and -independent mechanisms of fetal brain injury in the setting of preterm birth. Reprod Sci 19 (2012), 839–850.
107. Burd, I., Bentz, A.I., Chai, J., et al. Inflammation-induced preterm birth alters neuronal morphology in the mouse fetal brain. J Neurosci Res 88 (2010), 1872–1881.
108. Girard, S., Tremblay, L., Lepage, M., Sebire, G., IL-1 receptor antagonist protects against placental and neurodevelopmental defects induced by maternal inflammation. J Immunol 184 (2010), 3997–4005.
109. Leitner, K., Al Shammary, M., McLane, M., Johnston, M.V., Elovitz, M.A., Burd, I., IL-1 receptor blockade prevents fetal cortical brain injury but not preterm birth in a mouse model of inflammation-induced preterm birth and perinatal brain injury. Am J Reprod Immunol 71 (2014), 418–426.
110. Romero, R., Tartakovsky, B., The natural interleukin-1 receptor antagonist prevents interleukin-1-induced preterm delivery in mice. Am J Obstet Gynecol 167 (1992), 1041–1045.
111. Rosenzweig, J.M., Lei, J., Burd, I., Interleukin-1 receptor blockade in perinatal brain injury. Front Pediatr, 2, 2014, 108.
112. Dowling, J.K., O'Neill, L.A., Biochemical regulation of the inflammasome. Crit Rev Biochem Mol Biol 47 (2012), 424–443.
113. Kavathas, P.B., Boeras, C.M., Mulla, M.J., Abrahams, V.M., Nod1, but not the ASC inflammasome, contributes to induction of IL-1beta secretion in human trophoblasts after sensing of Chlamydia trachomatis. Mucosal Immunol 6 (2013), 235–243.
114. Pijnenborg, R., Vercruysse, L., Hanssens, M., The uterine spiral arteries in human pregnancy: facts and controversies. Placenta 27 (2006), 939–958.
115. Kaufmann, P., Black, S., Huppertz, B., Endovascular trophoblast invasion: implications for the pathogenesis of intrauterine growth retardation and preeclampsia. Biol Reprod 69 (2003), 1–7.
116. Wallace, A.E., Fraser, R., Cartwright, J.E., Extravillous trophoblast and decidual natural killer cells: a remodelling partnership. Hum Reprod Update 18 (2012), 458–471.
117. Ain, R., Canham, L.N., Soares, M.J., Gestation stage-dependent intrauterine trophoblast cell invasion in the rat and mouse: novel endocrine phenotype and regulation. Dev Biol 260 (2003), 176–190.
118. Konno, T., Rempel, L.A., Arroyo, J.A., Soares, M.J., Pregnancy in the brown Norway rat: a model for investigating the genetics of placentation. Biol Reprod 76 (2007), 709–718.
119. Pijnenborg, R., Vercruysse, L., Animal models of deep trophoblast invasion. 2010, Cambridge University Press, New York, 127–139.
120. Soares, M.J., Chakraborty, D., Karim Rumi, M.A., Konno, T., Renaud, S.J., Rat placentation: an experimental model for investigating the hemochorial maternal-fetal interface. Placenta 33 (2012), 233–243.
121. Soares, M.J., Chakraborty, D., Kubota, K., Renaud, S.J., Rumi, M.A., Adaptive mechanisms controlling uterine spiral artery remodeling during the establishment of pregnancy. Int J Dev Biol 58 (2014), 247–259.
122. Faria, T.N., Soares, M.J., Trophoblast cell differentiation: establishment, characterization, and modulation of a rat trophoblast cell line expressing members of the placental prolactin family. Endocrinology 129 (1991), 2895–2906.
123. Asanoma, K., Rumi, M.A., Kent, L.N., et al. FGF4-dependent stem cells derived from rat blastocysts differentiate along the trophoblast lineage. Dev Biol 351 (2011), 110–119.
124. Rosario, G.X., Konno, T., Soares, M.J., Maternal hypoxia activates endovascular trophoblast cell invasion. Dev Biol 314 (2008), 362–375.
125. Konno, T., Graham, A.R., Rempel, L.A., et al. Subfertility linked to combined luteal insufficiency and uterine progesterone resistance. Endocrinology 151 (2010), 4537–4550.
126. Konno, T., Rempel, L.A., Rumi, M.A., et al. Chromosome-substituted rat strains provide insights into the genetics of placentation. Physiol Genomics 43 (2011), 930–941.
127. Goyal, R., Yellon, S.M., Longo, L.D., Mata-Greenwood, E., Placental gene expression in a rat ‘model’ of placental insufficiency. Placenta 31 (2010), 568–575.
128. Goyal, R., Zhang, L., Blood, A.B., et al. Characterization of an animal model of pregnancy-induced vitamin D deficiency due to metabolic gene dysregulation. Am J Physiol Endocrinol Metab 306 (2014), E256–E266.
129. Lee, D.S., Rumi, M.A., Konno, T., Soares, M.J., In vivo genetic manipulation of the rat trophoblast cell lineage using lentiviral vector delivery. Genesis 47 (2009), 433–439.
130. Renaud, S.J., Karim Rumi, M.A., Soares, M.J., Review: genetic manipulation of the rodent placenta. Placenta 32:suppl 2 (2011), S130–S135.
131. Kent, L.N., Rumi, M.A., Kubota, K., Lee, D.S., Soares, M.J., FOSL1 is integral to establishing the maternal-fetal interface. Mol Cell Biol 31 (2011), 4801–4813.
132. Rumi, M.A., Dhakal, P., Kubota, K., et al. Generation of Esr1-knockout rats using zinc finger nuclease-mediated genome editing. Endocrinology 155 (2014), 1991–1999.
133. Chakraborty, D., Rumi, M.A., Konno, T., Soares, M.J., Natural killer cells direct hemochorial placentation by regulating hypoxia-inducible factor dependent trophoblast lineage decisions. Proc Natl Acad Sci U S A 108 (2011), 16295–16300.
134. Zhou, Y., Chiu, K., Brescia, R.J., et al. Increased depth of trophoblast invasion after chronic constriction of the lower aorta in rhesus monkeys. Am J Obstet Gynecol 169 (1993), 224–229.
135. Kadyrov, M., Schmitz, C., Black, S., Kaufmann, P., Huppertz, B., Pre-eclampsia and maternal anaemia display reduced apoptosis and opposite invasive phenotypes of extravillous trophoblast. Placenta 24 (2003), 540–548.
136. Zhang, J., Chen, Z., Smith, G.N., Croy, B.A., Natural killer cell-triggered vascular transformation: maternal care before birth?. Cell Mol Immunol 8 (2011), 1–11.
137. Rossant, J., Cross, J.C., Placental development: lessons from mouse mutants. Nat Rev Genet 2 (2001), 538–548.
138. Hou, Z., Romero, R., Uddin, M., Than, N.G., Wildman, D.E., Adaptive history of single copy genes highly expressed in the term human placenta. Genomics 93 (2009), 33–41.
139. Maltepe, E., Fisher, S.J., Placenta: the forgotten organ. Annu Rev Cell Dev Biol 31 (2015), 523–552.
140. Cox, B., Kotlyar, M., Evangelou, A.I., et al. Comparative systems biology of human and mouse as a tool to guide the modeling of human placental pathology. Mol Syst Biol, 5, 2009, 279.
141. Kent, L.N., Konno, T., Soares, M.J., Phosphatidylinositol 3 kinase modulation of trophoblast cell differentiation. BMC Dev Biol, 10, 2010, 97.
142. Renaud, S.J., Kubota, K., Rumi, M.A., Soares, M.J., The FOS transcription factor family differentially controls trophoblast migration and invasion. J Biol Chem 289 (2014), 5025–5039.
143. Genbacev, O., Lamb, J.D., Prakobphol, A., Donne, M., McMaster, M.T., Fisher, S.J., Human trophoblast progenitors: where do they reside?. Semin Reprod Med 31 (2013), 56–61.
144. Rossant, J., Cross, J.C., Placental development: lessons from mouse mutants. Nat Rev Genet 2 (2001), 538–548.
145. Cross, J.C., Baczyk, D., Dobric, N., et al. Genes, development and evolution of the placenta. Placenta 24 (2003), 123–130.
146. Davisson, R.L., Hoffmann, D.S., Butz, G.M., et al. Discovery of a spontaneous genetic mouse model of preeclampsia. Hypertension 39 (2002), 337–342.
147. Wong, A.Y., Kulandavelu, S., Whiteley, K.J., Qu, D., Langille, B.L., Adamson, S.L., Maternal cardiovascular changes during pregnancy and postpartum in mice. Am J Physiol Heart Circ Physiol 282 (2002), H918–H925.
148. Freemark, M., Placental hormones and the control of fetal growth. J Clin Endocrinol Metab 95 (2010), 2054–2057.
149. Brelje, T.C., Parsons, J.A., Sorenson, R.L., Regulation of islet beta-cell proliferation by prolactin in rat islets. Diabetes 43 (1994), 263–273.
150. Parsons, J.A., Brelje, T.C., Sorenson, R.L., Adaptation of islets of Langerhans to pregnancy: increased islet cell proliferation and insulin secretion correlates with the onset of placental lactogen secretion. Endocrinology 130 (1992), 1459–1466.
151. Weinhaus, A.J., Stout, L.E., Sorenson, R.L., Glucokinase, hexokinase, glucose transporter 2, and glucose metabolism in islets during pregnancy and prolactin-treated islets in vitro: mechanisms for long term up-regulation of islets. Endocrinology 137 (1996), 1640–1649.
152. Devlieger, R., Casteels, K., Van Assche, F.A., Reduced adaptation of the pancreatic B cells during pregnancy is the major causal factor for gestational diabetes: current knowledge and metabolic effects on the offspring. Acta Obstet Gynecol Scand 87 (2008), 1266–1270.
153. Zhang, H., Zhang, J., Pope, C.F., et al. Gestational diabetes mellitus resulting from impaired beta-cell compensation in the absence of FoxM1, a novel downstream effector of placental lactogen. Diabetes 59 (2010), 143–152.
154. Guimond, M.J., Wang, B., Fujita, J., Terhorst, C., Croy, B.A., Pregnancy-associated uterine granulated metrial gland cells in mutant and transgenic mice. Am J Reprod Immunol 35 (1996), 501–509.
155. Hu, D., Cross, J.C., Ablation of Tpbpa-positive trophoblast precursors leads to defects in maternal spiral artery remodeling in the mouse placenta. Dev Biol 358 (2011), 231–239.
156. Ashkar, A.A., Di Santo, J.P., Croy, B.A., Interferon gamma contributes to initiation of uterine vascular modification, decidual integrity, and uterine natural killer cell maturation during normal murine pregnancy. J Exp Med 192 (2000), 259–270.
157. Benirschke, K., Burton, G., Baergen, R., Early development of the human placenta. pathology of the human placenta. 6th ed., 2012, Springer, New York, 41–54.
158. Simmons, D.G., Rawn, S., Davies, A., Hughes, M., Cross, J.C., Spatial and temporal expression of the 23 murine Prolactin/Placental Lactogen-related genes is not associated with their position in the locus. BMC Genomics, 9, 2008, 352.
159. Gene Expression Omnibus (GEO) Datasets. Available at: http://www.ncbi.nlm.nih.gov/gds/. Accessed: June 3, 2015.
160. Brelje, T.C., Scharp, D.W., Lacy, P.E., et al. Effect of homologous placental lactogens, prolactins, and growth hormones on islet B-cell division and insulin secretion in rat, mouse, and human islets: implication for placental lactogen regulation of islet function during pregnancy. Endocrinology 132 (1993), 879–887.
161. Barbour, L.A., Shao, J., Qiao, L., et al. Human placental growth hormone causes severe insulin resistance in transgenic mice. Am J Obstet Gynecol 186 (2002), 512–517.
162. Branisteanu, D.D., Mathieu, C., Progesterone in gestational diabetes mellitus: guilty or not guilty?. Trends Endocrinol Metab 14 (2003), 54–56.
163. Fasshauer, M., Bluher, M., Stumvoll, M., Adipokines in gestational diabetes. Lancet Diabetes Endocrinol 2 (2014), 488–499.
164. Newbern, D., Freemark, M., Placental hormones and the control of maternal metabolism and fetal growth. Curr Opin Endocrinol Diabetes Obes 18 (2011), 409–416.
165. Chen, J., Tan, B., Karteris, E., et al. Secretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines. Diabetologia 49 (2006), 1292–1302.
166. Knox, K., Leuenberger, D., Penn, A.A., Baker, J.C., Global hormone profiling of murine placenta reveals Secretin expression. Placenta 32 (2011), 811–816.
167. Wiemers, D.O., Shao, L.J., Ain, R., Dai, G., Soares, M.J., The mouse prolactin gene family locus. Endocrinology 144 (2003), 313–325.
168. Galosy, S.S., Talamantes, F., Luteotropic actions of placental lactogens at midpregnancy in the mouse. Endocrinology 136 (1995), 3993–4003.
169. Chen, D., Dong, M., Fang, Q., He, J., Wang, Z., Yang, X., Alterations of serum resistin in normal pregnancy and pre-eclampsia. Clin Sci (Lond) 108 (2005), 81–84.
170. Tomimatsu, T., Yamaguchi, M., Murakami, T., et al. Increase of mouse leptin production by adipose tissue after midpregnancy: gestational profile of serum leptin concentration. Biochem Biophys Res Commun 240 (1997), 213–215.
171. Combs, T.P., Berg, A.H., Rajala, M.W., et al. Sexual differentiation, pregnancy, calorie restriction, and aging affect the adipocyte-specific secretory protein adiponectin. Diabetes 52 (2003), 268–276.
172. Ling, C., Kindblom, J., Wennbo, H., Billig, H., Increased resistin expression in the adipose tissue of male prolactin transgenic mice and in male mice with elevated androgen levels. FEBS Lett 507 (2001), 147–150.
173. Viengchareun, S., Bouzinba-Segard, H., Laigneau, J.P., et al. Prolactin potentiates insulin-stimulated leptin expression and release from differentiated brown adipocytes. J Mol Endocrinol 33 (2004), 679–691.
174. Asai-Sato, M., Okamoto, M., Endo, M., et al. Hypoadiponectinemia in lean lactating women: Prolactin inhibits adiponectin secretion from human adipocytes. Endocr J 53 (2006), 555–562.
175. Tunster, S.J., Creeth, H.D., John, R.M., The imprinted Phlda2 gene modulates a major endocrine compartment of the placenta to regulate placental demands for maternal resources. Dev Biol 409 (2016), 251–260.
176. Chen, P.Y., Ganguly, A., Rubbi, L., et al. Intrauterine calorie restriction affects placental DNA methylation and gene expression. Physiol Genom 45 (2013), 565–576.
177. 2 goes to: preservation of human fetal oxygen delivery and consumption at high altitude. J Physiol 587 (2009), 693–708.
178. Faber, J.J., Review of flow limited transfer in the placenta. Int J Obstet Anesth 4 (1995), 230–237.
179. Ansari, T., Fenlon, S., Pasha, S., et al. Morphometric assessment of the oxygen diffusion conductance in placentae from pregnancies complicated by intra-uterine growth restriction. Placenta 24 (2003), 618–626.
180. Mayhew, T.M., Scaling placental oxygen diffusion to birthweight: studies on placentae from low- and high-altitude pregnancies. J Anat 175 (1991), 187–194.
181. Mayhew, T.M., Joy, C.F., Haas, J.D., Structure-function correlation in the human placenta: the morphometric diffusing capacity for oxygen at full term. J Anat 139 (1984), 691–708.
182. Reshetnikova, O.S., Burton, G.J., Milovanov, A.P., Effects of hypobaric hypoxia on the fetoplacental unit: the morphometric diffusing capacity of the villous membrane at high altitude. Am J Obstet Gynecol 171 (1994), 1560–1565.
183. Jauniaux, E., Watson, A.L., Hempstock, J., Bao, Y.P., Skepper, J.N., Burton, G.J., Onset of maternal arterial blood flow and placental oxidative stress: a possible factor in human early pregnancy failure. Am J Pathol 157 (2000), 2111–2122.
184. Jauniaux, E., Watson, A., Burton, G., Evaluation of respiratory gases and acid-base gradients in human fetal fluids and uteroplacental tissue between 7 and 16 weeks’ gestation. Am J Obstet Gynecol 184 (2001), 998–1003.
185. Rodesch, F., Simon, P., Donner, C., Jauniaux, E., Oxygen measurements in endometrial and trophoblastic tissues during early pregnancy. Obstet Gynecol 80 (1992), 283–285.
186. Soothill, P.W., Nicolaides, K.H., Rodeck, C.H., Campbell, S., Effect of gestational age on fetal and intervillous blood gas and acid-base values in human pregnancy. Fetal Ther 1 (1986), 168–175.
187. Lackman, F., Capewell, V., Gagnon, R., Richardson, B., Fetal umbilical cord oxygen values and birth to placental weight ratio in relation to size at birth. Am J Obstet Gynecol 185 (2001), 674–682.
188. Kuzmina, I.Y., Hubina-Vakulik, G.I., Burton, G.J., Placental morphometry and Doppler flow velocimetry in cases of chronic human fetal hypoxia. Eur J Obstet Gynecol Reprod Biol 120 (2005), 139–145.
189. Rajakumar, A., Whitelock, K.A., Weissfeld, L.A., Daftary, A.R., Markovic, N., Conrad, K.P., Selective overexpression of the hypoxia-inducible transcription factor, HIF-2alpha, in placentas from women with preeclampsia. Biol Reprod 64 (2001), 499–506.
190. Rampersad, R., Nelson, D.M., Trophoblast biology, responses to hypoxia and placental dysfunction in preeclampsia. Front Biosci 12 (2007), 2447–2456.
191. Soleymanlou, N., Jurisica, I., Nevo, O., et al. Molecular evidence of placental hypoxia in preeclampsia. J Clin Endocrinol Metab 90 (2005), 4299–4308.
192. Tal, R., The role of hypoxia and hypoxia-inducible factor-1alpha in preeclampsia pathogenesis. Biol Reprod, 87, 2012, 134.
193. Yinon, Y., Nevo, O., Xu, J., et al. Severe intrauterine growth restriction pregnancies have increased placental endoglin levels: hypoxic regulation via transforming growth factor-beta 3. Am J Pathol 172 (2008), 77–85.
194. Taricco, E., Radaelli, T., Rossi, G., et al. Effects of gestational diabetes on fetal oxygen and glucose levels in vivo. BJOG 116 (2009), 1729–1735.
195. Escobar, J., Teramo, K., Stefanovic, V., et al. Amniotic fluid oxidative and nitrosative stress biomarkers correlate with fetal chronic hypoxia in diabetic pregnancies. Neonatology 103 (2013), 193–198.
196. Hytinantti, T.K., Koistinen, H.A., Teramo, K., Karonen, S.L., Koivisto, V.A., Andersson, S., Increased fetal leptin in type I diabetes mellitus pregnancies complicated by chronic hypoxia. Diabetologia 43 (2000), 709–713.
197. Todros, T., Sciarrone, A., Piccoli, E., Guiot, C., Kaufmann, P., Kingdom, J., Umbilical Doppler waveforms and placental villous angiogenesis in pregnancies complicated by fetal growth restriction. Obstet Gynecol 93 (1999), 499–503.
198. Ayuk, P.T., Theophanous, D., D'Souza, S.W., Sibley, C.P., Glazier, J.D., L-arginine transport by the microvillus plasma membrane of the syncytiotrophoblast from human placenta in relation to nitric oxide production: effects of gestation, preeclampsia, and intrauterine growth restriction. J Clin Endocrinol Metab 87 (2002), 747–751.
199. Ferrazzi, E., Rigano, S., Bozzo, M., et al. Umbilical vein blood flow in growth-restricted fetuses. Ultrasound Obstet Gynecol 16 (2000), 432–438.
200. Aardema, M.W., Oosterhof, H., Timmer, A., Van Rooy, I., Aarnoudse, J.G., Uterine artery Doppler flow and uteroplacental vascular pathology in normal pregnancies and pregnancies complicated by pre-eclampsia and small for gestational age fetuses. Placenta 22 (2001), 405–411.
201. Yu, C.K., Smith, G.C., Papageorghiou, A.T., Cacho, A.M., Nicolaides, K.H., An integrated model for the prediction of pre-eclampsia using maternal factors and uterine artery Doppler velocimetry in unselected low-risk women. Am J Obstet Gynecol, 195, 2006, 330.
202. Rigano, S., Bozzo, M., Ferrazzi, E., Bellotti, M., Battaglia, F.C., Galan, H.L., Early and persistent reduction in umbilical vein blood flow in the growth-restricted fetus: a longitudinal study. Am J Obstet Gynecol 185 (2001), 834–838.
203. Rigano, S., Bozzo, M., Padoan, A., et al. Small size-specific umbilical vein diameter in severe growth restricted fetuses that die in utero. Prenat Diagn 28 (2008), 908–913.
204. Bellotti, M., Pennati, G., De Gasperi, C., Bozzo, M., Battaglia, F.C., Ferrazzi, E., Simultaneous measurements of umbilical venous, fetal hepatic, and ductus venosus blood flow in growth-restricted human fetuses. Am J Obstet Gynecol 190 (2004), 1347–1358.
205. Widness, J.A., Susa, J.B., Garcia, J.F., et al. Increased erythropoiesis and elevated erythropoietin in infants born to diabetic mothers and in hyperinsulinemic rhesus fetuses. J Clin Invest 67 (1981), 637–642.
206. Zamudio, S., Wu, Y., Ietta, F., et al. Human placental hypoxia-inducible factor-1alpha expression correlates with clinical outcomes in chronic hypoxia in vivo. Am J Pathol 170 (2007), 2171–2179.
207. Nevo, O., Soleymanlou, N., Wu, Y., et al. Increased expression of sFlt-1 in in vivo and in vitro models of human placental hypoxia is mediated by HIF-1. Am J Physiol Regul Integr Comp Physiol 291 (2006), R1085–R1093.
208. Rajakumar, A., Doty, K., Daftary, A., Harger, G., Conrad, K.P., Impaired oxygen-dependent reduction of HIF-1alpha and -2alpha proteins in pre-eclamptic placentae. Placenta 24 (2003), 199–208.
209. Rajakumar, A., Brandon, H.M., Daftary, A., Ness, R., Conrad, K.P., Evidence for the functional activity of hypoxia-inducible transcription factors overexpressed in preeclamptic placentae. Placenta 25 (2004), 763–769.
210. Eltzschig, H.K., Carmeliet, P., Hypoxia and inflammation. N Engl J Med 364 (2011), 656–665.
211. Combined antioxidant and preeclampsia prediction studies (CAPPS). Available at: https://clinicaltrials.gov/ct2/show/NCT00135707?term=NCT00135707&rank=1. Accessed May 1, 2015.
212. Effect of low dose aspirin on birthweight in twins: the GAP Trial. Available at: https://clinicaltrials.gov/ct2/show/NCT02280031?term=NCT02280031&rank=1. Accessed May 1, 2015.
213. Pravastatin for prevention of preeclampsia. Available at: https://clinicaltrials.gov/ct2/show/NCT01717586?term=NCT01717586&rank=1. Accessed May 1, 2015.
214. RCT of antioxidant therapy to prevent preeclampsia in Brazil. Available at: https://clinicaltrials.gov/ct2/show/NCT00097110?term=NCT00097110&rank=1. Accessed May 1, 2015.
215. Caniggia, I., Winter, J., Lye, S.J., Post, M., Oxygen and placental development during the first trimester: implications for the pathophysiology of pre-eclampsia. Placenta 21:suppl A (2000), S25–S30.
216. Rajakumar, A., Jeyabalan, A., Markovic, N., Ness, R., Gilmour, C., Conrad, K.P., Placental HIF-1 alpha, HIF-2 alpha, membrane and soluble VEGF receptor-1 proteins are not increased in normotensive pregnancies complicated by late-onset intrauterine growth restriction. Am J Physiol Regul Integr Comp Physiol 293 (2007), R766–R774.
217. Kingdom, J.C., Kaufmann, P., Oxygen and placental vascular development. Adv Exp Med Biol 474 (1999), 259–275.
218. Kingdom, J.C., Kaufmann, P., Oxygen and placental villous development: origins of fetal hypoxia. Placenta 18 (1997), 613–621 discussion 23-6.
219. Unger, C., Weiser, J.K., McCullough, R.E., Keefer, S., Moore, L.G., Altitude, low birth weight, and infant mortality in Colorado. JAMA 259 (1988), 3427–3432.
220. Krampl, E., Lees, C., Bland, J.M., Espinoza Dorado, J., Moscoso, G., Campbell, S., Fetal biometry at 4300 m compared to sea level in Peru. Ultrasound Obstet Gynecol 16 (2000), 9–18.
221. Zamudio, S., The placenta at high altitude. High Alt Med Biol 4 (2003), 171–191.
222. Espinoza, J., Sebire, N.J., McAuliffe, F., Krampl, E., Nicolaides, K.H., Placental villus morphology in relation to maternal hypoxia at high altitude. Placenta 22 (2001), 606–608.
223. Mayhew, T.M., Thinning of the intervascular tissue layers of the human placenta is an adaptive response to passive diffusion in vivo and may help to predict the origins of fetal hypoxia. Eur J Obstet Gynecol Reprod Biol 81 (1998), 101–109.
224. Mayhew, T.M., Charnock-Jones, D.S., Kaufmann, P., Aspects of human fetoplacental vasculogenesis and angiogenesis: III, changes in complicated pregnancies. Placenta 25 (2004), 127–139.
225. Illsley, N.P., Caniggia, I., Zamudio, S., Placental metabolic reprogramming: do changes in the mix of energy-generating substrates modulate fetal growth?. Int J Dev Biol 54 (2010), 409–419.
226. Zamudio, S., Torricos, T., Fik, E., et al. Hypoglycemia and the origin of hypoxia-induced reduction in human fetal growth. PLoS One, 5, 2010, e8551.
227. Lu, H., Forbes, R.A., Verma, A., Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. J Biol Chem 277 (2002), 23111–23115.
228. Semenza, G.L., Oxygen-dependent regulation of mitochondrial respiration by hypoxia-inducible factor 1. Biochem J 405 (2007), 1–9.
229. Lisy, K., Peet, D.J., Turn me on: regulating HIF transcriptional activity. Cell Death Differ 15 (2008), 642–649.
230. Aragones, J., Fraisl, P., Baes, M., Carmeliet, P., Oxygen sensors at the crossroad of metabolism. Cell Metab 9 (2009), 11–22.
231. Wilber, R.L., Stray-Gundersen, J., Levine, B.D., Effect of hypoxic “dose” on physiological responses and sea-level performance. Med Sci Sports Exerc 39 (2007), 1590–1599.
232. Sifakis, S., Angelakis, E., Vardaki, E., Koumantaki, Y., Matalliotakis, I., Koumantakis, E., Erythropoietin in the treatment of iron deficiency anemia during pregnancy. Gynecol Obstet Invest 51 (2001), 150–156.
233. Zamudio, S., Postigo, L., Illsley, N.P., et al. Maternal oxygen delivery is not related to altitude- and ancestry-associated differences in human fetal growth. J Physiol 582 (2007), 883–895.
234. Hudetz, A.G., Wood, J.D., Biswal, B.B., Krolo, I., Kampine, J.P., Effect of hemodilution on RBC velocity, supply rate, and hematocrit in the cerebral capillary network. J Appl Physiol 87 (1999), 505–509.
235. Say, L., Gulmezoglu, A.M., Hofmeyr, G.J., Maternal oxygen administration for suspected impaired fetal growth. Cochrane Database Syst Rev, 2003, CD000137.
236. Zamudio, S., High-altitude hypoxia and preeclampsia. Front Biosci 12 (2007), 2967–2977.
237. Galan, H.L., Ferrazzi, E., Hobbins, J.C., Intrauterine growth restriction (IUGR): biometric and Doppler assessment. Prenat Diagn 22 (2002), 331–337.
238. Giles, W.B., Trudinger, B.J., Baird, P.J., Fetal umbilical artery flow velocity waveforms and placental resistance: pathological correlation. BJOG 92 (1985), 31–38.
239. Macara, L., Kingdom, J.C., Kohnen, G., Bowman, A.W., Greer, I.A., Kaufmann, P., Elaboration of stem villous vessels in growth restricted pregnancies with abnormal umbilical artery Doppler waveforms. BJOG 102 (1995), 807–812.
240. Kreczy, A., Fusi, L., Wigglesworth, J.S., Correlation between umbilical arterial flow and placental morphology. Int J Gynecol Pathol 14 (1995), 306–309.
241. Palmer, S.K., Zamudio, S., Coffin, C., Parker, S., Stamm, E., Moore, L.G., Quantitative estimation of human uterine artery blood flow and pelvic blood flow redistribution in pregnancy. Obstet Gynecol 80 (1992), 1000–1006.
242. Mandala, M., Osol, G., Physiological remodelling of the maternal uterine circulation during pregnancy. Basic Clin Pharmacol Toxicol 110 (2012), 12–18.
243. Osol, G., Mandala, M., Maternal uterine vascular remodeling during pregnancy. Physiology (Bethesda) 24 (2009), 58–71.
244. Osol, G., Cipolla, M., Interaction of myogenic and adrenergic mechanisms in isolated, pressurized uterine radial arteries from late-pregnant and nonpregnant rats. Am J Obstet Gynecol 168 (1993), 697–705.
245. Senadheera, S., Bertrand, P.P., Grayson, T.H., Leader, L., Murphy, T.V., Sandow, S.L., Pregnancy-induced remodelling and enhanced endothelium-derived hyperpolarization-type vasodilator activity in rat uterine radial artery: transient receptor potential vanilloid type 4 channels, caveolae and myoendothelial gap junctions. J Anat 223 (2013), 677–686.
246. Luksha, L., Nisell, H., Luksha, N., Kublickas, M., Hultenby, K., Kublickiene, K., Endothelium-derived hyperpolarizing factor in preeclampsia: heterogeneous contribution, mechanisms, and morphological prerequisites. Am J Physiol Regul Integr Comp Physiol 294 (2008), R510–R519.
247. Boyd, P.A., Scott, A., Quantitative structural studies on human placentas associated with pre-eclampsia, essential hypertension and intrauterine growth retardation. BJOG 92 (1985), 714–721.
248. Teasdale, F., Histomorphometry of the human placenta in maternal preeclampsia. Am J Obstet Gynecol 152 (1985), 25–31.
249. Geva, E., Ginzinger, D.G., Zaloudek, C.J., Moore, D.H., Byrne, A., Jaffe, R.B., Human placental vascular development: vasculogenic and angiogenic (branching and nonbranching) transformation is regulated by vascular endothelial growth factor-A, angiopoietin-1, and angiopoietin-2. J Clin Endocrinol Metab 87 (2002), 4213–4224.
250. Ratnikov, B., Aza-Blanc, P., Ronai, Z.A., Smith, J.W., Osterman, A.L., Scott, D.A., Glutamate and asparagine cataplerosis underlie glutamine addiction in melanoma. Oncotarget 6 (2015), 7379–7389.
251. Wise, D.R., Thompson, C.B., Glutamine addiction: a new therapeutic target in cancer. Trends Biochem Sci 35 (2010), 427–433.
252. Medvetz, D., Priolo, C., Henske, E.P., Therapeutic targeting of cellular metabolism in cells with hyperactive mTORC1: a paradigm shift. Mol Cancer Res 13 (2015), 3–8.
253. Vivanco, I., Targeting molecular addictions in cancer. Br J Cancer 111 (2014), 2033–2038.
254. Legband, N.D., Feshitan, J.A., Borden, M.A., Terry, B.S., Evaluation of peritoneal microbubble oxygenation therapy in a rabbit model of hypoxemia. IEEE Trans Biomed Eng 62 (2015), 1376–1382.
255. Matsuki, N., Ishikawa, T., Ichiba, S., Shiba, N., Ujike, Y., Yamaguchi, T., Oxygen supersaturated fluid using fine micro/nanobubbles. Int J Nanomedicine 9 (2014), 4495–4505.
256. Matsuki, N., Ichiba, S., Ishikawa, T., et al. Blood oxygenation using microbubble suspensions. Eur Biophys J 41 (2012), 571–578.
257. Bisazza, A., Giustetto, P., Rolfo, A., et al. Microbubble-mediated oxygen delivery to hypoxic tissues as a new therapeutic device. Conf Proc IEEE Eng Med Biol Soc 2008 (2008), 2067–2070.
258. Hammond, S., Mathewson, A.M., Baker, P.N., Mayhew, T.M., Dunn, W.R., Gap junctions and hydrogen peroxide are involved in endothelium-derived hyperpolarising responses to bradykinin in omental arteries and veins isolated from pregnant women. Eur J Pharmacol 668 (2011), 225–232.
259. Vodstrcil, L.A., Tare, M., Novak, J., et al. Relaxin mediates uterine artery compliance during pregnancy and increases uterine blood flow. FASEB J 26 (2012), 4035–4044.
260. Morton, J.S., Davidge, S.T., Arterial endothelium-derived hyperpolarization: potential role in pregnancy adaptations and complications. J Cardiovasc Pharmacol 61 (2013), 197–203.
261. Vadillo-Ortega, F., Perichart-Perera, O., Espino, S., et al. Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial. BMJ, 342, 2011, d2901.
262. Staff, A.C., Berge, L., Haugen, G., Lorentzen, B., Mikkelsen, B., Henriksen, T., Dietary supplementation with L-arginine or placebo in women with pre-eclampsia. Acta Obstet Gynecol Scand 83 (2004), 103–107.
263. Ganzevoort, W., Alfirevic, Z., Von Dadelszen, P., et al. STRIDER: Sildenafil Therapy In Dismal prognosis Early-onset intrauterine growth Restriction: a protocol for a systematic review with individual participant data and aggregate data meta-analysis and trial sequential analysis. Syst Rev, 3, 2014, 23.
264. Von Dadelszen, P., Dwinnell, S., Magee, L.A., et al. Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 118 (2011), 624–628.
265. Everrest, D.A., Developing a therapy for fetal growth restriction: a 6 year prospective study to define the clinical and biological characteristic of pregnancies affected by severe early onset fetal growth restriction. 2015, University College, London.
266. David, A.L., Torondel, B., Zachary, I., et al. Local delivery of VEGF adenovirus to the uterine artery increases vasorelaxation and uterine blood flow in the pregnant sheep. Gene Ther 15 (2008), 1344–1350.
267. Hanauske-Abel, H.M., Popowicz, A.M., The HAG mechanism: a molecular rationale for the therapeutic application of iron chelators in human diseases involving the 2-oxoacid utilizing dioxygenases. Curr Med Chem 10 (2003), 1005–1019.
268. Hoque, M., Hanauske-Abel, H.M., Palumbo, P., et al. Inhibition of HIV-1 gene expression by ciclopirox and deferiprone, drugs that prevent hypusination of eukaryotic initiation factor 5A. Retrovirology, 6, 2009, 90.
269. Zhang, E.G., Burton, G.J., Smith, S.K., Charnock-Jones, D.S., Placental vessel adaptation during gestation and to high altitude: changes in diameter and perivascular cell coverage. Placenta 23 (2002), 751–762.
270. Charnock-Jones, D.S., Soluble flt-1 and the angiopoietins in the development and regulation of placental vasculature. J Anat 200 (2002), 607–615.
271. Shih, S.C., Ju, M., Liu, N., Mo, J.R., Ney, J.J., Smith, L.E., Transforming growth factor beta1 induction of vascular endothelial growth factor receptor 1: mechanism of pericyte-induced vascular survival in vivo. Proc Natl Acad Sci U S A 100 (2003), 15859–15864.
272. Zamudio, S., Baumann, M.U., Illsley, N.P., Effects of chronic hypoxia in vivo on the expression of human placental glucose transporters. Placenta 27 (2006), 49–55.
273. Gaither, K., Quraishi, A.N., Illsley, N.P., Diabetes alters the expression and activity of the human placental GLUT1 glucose transporter. J Clin Endocrinol Metab 84 (1999), 695–701.
274. Glazier, J.D., Cetin, I., Perugino, G., et al. Association between the activity of the system A amino acid transporter in the microvillus plasma membrane of the human placenta and severity of fetal compromise in intrauterine growth restriction. Pediatr Res 42 (1997), 514–519.
275. Jansson, T., Ekstrand, Y., Bjorn, C., Wennergren, M., Powell, T.L., Alterations in the activity of placental amino acid transporters in pregnancies complicated by diabetes. Diabetes 51 (2002), 2214–2219.
276. Harding, J.E., Owens, J.A., Robinson, J.S., Should we try to supplement the growth retarded fetus? A cautionary tale. BJOG 99 (1992), 707–709.
277. Zamudio, S., Torricos, T., Fik, E., et al. Hypoglycemia and the origin of hypoxia-induced reduction in human fetal growth. PLoS One, 5, 2010, e8551.
278. Jansson, T., Wennergren, M., Illsley, N.P., Glucose transporter protein expression in human placenta throughout gestation and in intrauterine growth retardation. J Clin Endocrinol Metab 77 (1993), 1554–1562.
279. Brown, K., Heller, D.S., Zamudio, S., Illsley, N.P., Glucose transporter 3 (GLUT3) protein expression in human placenta across gestation. Placenta 32 (2011), 1041–1049.
280. Cleal, J.K., Lewis, R.M., The mechanisms and regulation of placental amino acid transport to the human foetus. J Neuroendocrinol 20 (2008), 419–426.
281. Baumann, M., Schneider, H., Malek, A., et al. Regulation of human trophoblast GLUT1 glucose transporter by insulin-like growth factor I (IGF-I). PLoS One, 9, 2014, e106037.
282. Roos, S., Lagerlof, O., Wennergren, M., Powell, T.L., Jansson, T., Regulation of amino acid transporters by glucose and growth factors in cultured primary human trophoblast cells is mediated by mTOR signaling. Am J Physiol Cell Physiol 297 (2009), C723–C731.
283. Giudice, L.C., Martina, N.A., Crystal, R.A., Tazuke, S., Druzin, M., Insulin-like growth factor binding protein-1 at the maternal-fetal interface and insulin-like growth factor-I, insulin-like growth factor-II, and insulin-like growth factor binding protein-1 in the circulation of women with severe preeclampsia. Am J Obstet Gynecol 176 (1997), 751–758.
284. Sferruzzi-Perri, A.N., Owens, J.A., Pringle, K.G., Roberts, C.T., The neglected role of insulin-like growth factors in the maternal circulation regulating fetal growth. J Physiol 589 (2011), 7–20.
285. Jones, H.N., Crombleholme, T., Habli, M., Adenoviral-mediated placental gene transfer of IGF-1 corrects placental insufficiency via enhanced placental glucose transport mechanisms. PLoS One, 8, 2013, e74632.
286. Jones, H., Crombleholme, T., Habli, M., Regulation of amino acid transporters by adenoviral-mediated human insulin-like growth factor-1 in a mouse model of placental insufficiency in vivo and the human trophoblast line BeWo in vitro. Placenta 35 (2014), 132–138.
287. Laplante, M., Sabatini, D.M., mTOR signaling in growth control and disease. Cell 149 (2012), 274–293.
288. Jansson, N., Rosario, F.J., Gaccioli, F., et al. Activation of placental mTOR signaling and amino acid transporters in obese women giving birth to large babies. J Clin Endocrinol Metab 98 (2013), 105–113.
289. Aiko, Y., Askew, D.J., Aramaki, S., et al. Differential levels of amino acid transporters System L and ASCT2, and the mTOR protein in placenta of preeclampsia and IUGR. BMC Pregnancy Childbirth, 14, 2014, 181.
290. Roos, S., Jansson, N., Palmberg, I., Saljo, K., Powell, T.L., Jansson, T., Mammalian target of rapamycin in the human placenta regulates leucine transport and is down-regulated in restricted fetal growth. J Physiol 582 (2007), 449–459.
291. Choi, Y.J., Park, Y.J., Park, J.Y., et al. Inhibitory effect of mTOR activator MHY1485 on autophagy: suppression of lysosomal fusion. PLoS One, 7, 2012, e43418.
292. Peng, N., Meng, N., Wang, S., et al. An activator of mTOR inhibits oxLDL-induced autophagy and apoptosis in vascular endothelial cells and restricts atherosclerosis in apolipoprotein E(-)/(-) mice. Sci Rep, 4, 2014, 5519.
293. Rosario, F.J., Kanai, Y., Powell, T.L., Jansson, T., Mammalian target of rapamycin signalling modulates amino acid uptake by regulating transporter cell surface abundance in primary human trophoblast cells. J Physiol 591 (2013), 609–625.
294. Andrzejewski, S., Gravel, S.P., Pollak, M., St-Pierre, J., Metformin directly acts on mitochondria to alter cellular bioenergetics. Cancer Metab, 2, 2014, 12.
295. Illsley, N.P., Caniggia, I., Zamudio, S., Placental metabolic reprogramming: do changes in the mix of energy-generating substrates modulate fetal growth?. Int J Dev Biol 54 (2010), 409–419.
296. Myatt, L., Cui, X., Oxidative stress in the placenta. Histochem Cell Biol 122 (2004), 369–382.
297. Menon, R., Oxidative stress damage as a detrimental factor in preterm birth pathology. Front Immunol, 5, 2014, 567.
298. Abuja, P.M., Albertini, R., Methods for monitoring oxidative stress, lipid peroxidation and oxidation resistance of lipoproteins. Clin Chim Acta 306 (2001), 1–17.
299. Roberts, V.H., Smith, J., McLea, S.A., Heizer, A.B., Richardson, J.L., Myatt, L., Effect of increasing maternal body mass index on oxidative and nitrative stress in the human placenta. Placenta 30 (2009), 169–175.
300. Macmillan-Crow, L.A., Crow, J.P., Kerby, J.D., Beckman, J.S., Thompson, J.A., Nitration and inactivation of manganese superoxide dismutase in chronic rejection of human renal allografts. Proc Natl Acad Sci U S A 93 (1996), 11853–11858.
301. Ischiropoulos, H., Biological tyrosine nitration: a pathophysiological function of nitric oxide and reactive oxygen species. Arch Biochem Biophys 356 (1998), 1–11.
302. Pacher, P., Beckman, J.S., Liaudet, L., Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87 (2007), 315–424.
303. Myatt, L., Review: reactive oxygen and nitrogen species and functional adaptation of the placenta. Placenta 31:suppl (2010), S66–S69.
304. Sen, C.K., Packer, L., Antioxidant and redox regulation of gene transcription. FASEB J 10 (1996), 709–720.
305. Halliwell, B., Whiteman, M., Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean?. Br J Pharmacol 142 (2004), 231–255.
306. Muralimanoharan, S., Guo, C., Myatt, L., Maloyan, A., Sexual dimorphism in miR-210 expression and mitochondrial dysfunction in the placenta with maternal obesity. Int J Obes (Lond) 39 (2015), 1274–1281.
307. Roberts, J.M., Myatt, L., Spong, C.Y., et al. Vitamins C and E to prevent complications of pregnancy-associated hypertension. N Engl J Med 362 (2010), 1282–1291.
308. Kelso, G.F., Porteous, C.M., Coulter, C.V., et al. Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties. J Biol Chem 276 (2001), 4588–4596.
309. Khera, A., Vanderlelie, J.J., Perkins, A.V., Selenium supplementation protects trophoblast cells from mitochondrial oxidative stress. Placenta 34 (2013), 594–598.
310. Reiter, R.J., Tan, D.X., Mayo, J.C., Sainz, R.M., Leon, J., Czarnocki, Z., Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans. Acta Biochim Pol 50 (2003), 1129–1146.
311. Muralimanoharan, S., Maloyan, A., Mele, J., Guo, C., Myatt, L.G., Myatt, L., MIR-210 modulates mitochondrial respiration in placenta with preeclampsia. Placenta 33 (2012), 816–823.
312. Vatten, L.J., Skjaerven, R., Offspring sex and pregnancy outcome by length of gestation. Early Hum Dev 76 (2004), 47–54.
313. Clifton, V.L., Review: sex and the human placenta: mediating differential strategies of fetal growth and survival. Placenta 31:suppl (2010), S33–S39.
314. Sood, R., Zehnder, J.L., Druzin, M.L., Brown, P.O., Gene expression patterns in human placenta. Proc Natl Acad Sci U S A 103 (2006), 5478–5483.
315. Muralimanoharan, S., Maloyan, A., Myatt, L., Evidence of sexual dimorphism in the placental function with severe preeclampsia. Placenta 34 (2013), 1183–1189.
316. Arrowsmith, J., Miller, P., Trial watch: phase II and phase III attrition rates 2011-2012. Nat Rev Drug Discov, 12, 2013, 569.
317. Mullard, A., Drug repurposing programmes get lift off. Nat Rev Drug Discov 11 (2012), 505–506.
318. The National Center for Advancing Translational Sciences (NCATS). Available at: http://www.ncats.nih.gov/ntu. Accessed May 1, 2015.
319. Reviewer guidance: evaluating the risks of drug exposure in human pregnancies. Available at: http://www.fda.gov/downloads/ScienceResearch/SpecialTopics/WomensHealthResearch/UCM133359.pdf. Accessed May 1, 2015.
320. Shineman, D.W., Alam, J., Anderson, M., et al. Overcoming obstacles to repurposing for neurodegenerative disease. Ann Clin Transl Neurol 1 (2014), 512–518.
321. Mitchell, A.A., Gilboa, S.M., Werler, M.M., Kelley, K.E., Louik, C., Hernandez-Diaz, S., Medication use during pregnancy, with particular focus on prescription drugs: 1976-2008. Am J Obstet Gynecol 205 (2011), 51.e1–51.e8.
322. Lupattelli, A., Spigset, O., Twigg, M.J., et al. Medication use in pregnancy: a cross-sectional, multinational web-based study. BMJ Open, 4, 2014.
323. Andrade, S.E., Raebel, M.A., Morse, A.N., et al. Use of prescription medications with a potential for fetal harm among pregnant women. Pharmacoepidemiol Drug Saf 15 (2006), 546–554.
324. Andrade, S.E., Gurwitz, J.H., Davis, R.L., et al. Prescription drug use in pregnancy. Am J Obstet Gynecol 191 (2004), 398–407.
325. Andrade, S.E., Raebel, M.A., Brown, J., et al. Use of antidepressant medications during pregnancy: a multisite study. Am J Obstet Gynecol 198 (2008), 194.e1–194.e5.
326. Anderson, G.D., Pregnancy-induced changes in pharmacokinetics: a mechanistic-based approach. Clin Pharmacokinet 44 (2005), 989–1008.
327. Anger, G.J., Piquette-Miller, M., Pharmacokinetic studies in pregnant women. Clin Pharmacol Ther 83 (2008), 184–187.
328. Costantine, M.M., Physiologic and pharmacokinetic changes in pregnancy. Front Pharmacol, 5, 2014, 65.
329. Briggs, G., Freeman, R., Yaffe, S., Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. 2012, Lippincott, Williams and Wilkins, Philadelphia.
330. Pacheco, L.D., MM, C., Hankins, G.D., Physiologic changes during pregnancy. Mattison, D.R., (eds.) Clinical pharmacology during pregnancy, 2013, Elsevier, London, 5–14.
331. Robson, S.C., Hunter, S., Boys, R.J., Dunlop, W., Serial study of factors influencing changes in cardiac output during human pregnancy. Am J Physiol 256 (1989), H1060–H1065.
332. Clark, S.L., Cotton, D.B., Lee, W., et al. Central hemodynamic assessment of normal term pregnancy. Am J Obstet Gynecol 161 (1989), 1439–1442.
333. Hytten, F.E., Paintin, D.B., Increase in plasma volume during normal pregnancy. J Obstet Gynaecol Br Emp 70 (1963), 402–407.
334. Frederiksen, M.C., Physiologic changes in pregnancy and their effect on drug disposition. Semin Perinatol 25 (2001), 120–123.
335. Elkus, R., Popovich, J. Jr., Respiratory physiology in pregnancy. Clin Chest Med 13 (1992), 555–565.
336. Parry, E., Shields, R., Turnbull, A.C., Transit time in the small intestine in pregnancy. J Obstet Gynaecol Br Commonw 77 (1970), 900–901.
337. Evans, W.E., Relling, M.V., Pharmacogenomics: translating functional genomics into rational therapeutics. Science 286 (1999), 487–491.
338. Hellden, A., Madadi, P., Pregnancy and pharmacogenomics in the context of drug metabolism and response. Pharmacogenomics 14 (2013), 1779–1791.
339. Ke, A.B., Rostami-Hodjegan, A., Zhao, P., Unadkat, J.D., Pharmacometrics in pregnancy: an unmet need. Annu Rev Pharmacol Toxicol 54 (2014), 53–69.
340. Weier, N., He, S.M., Li, X.T., Wang, L.L., Zhou, S.F., Placental drug disposition and its clinical implications. Curr Drug Metab 9 (2008), 106–121.
341. Koren, G., Sex dependent pharmacokinetics and bioequivalence: time for a change. J Popul Ther Clin Pharmacol 20 (2013), e358–e361.
342. Shields, K.E., Lyerly, A.D., Exclusion of pregnant women from industry-sponsored clinical trials. Obstet Gynecol 122 (2013), 1077–1081.
343. Schonfeld, T., Schmid, K.K., Brown, J.S., Amoura, N.J., Gordon, B., A pregnancy testing policy for women enrolled in clinical trials. IRB 35 (2013), 9–15.
344. McCormack, S.A., Best, B.M., Obstetric pharmacokinetic dosing studies are urgently needed. Front Pediatr, 2, 2014, 9.
345. Meslin, E.M., Blasimme, A., Cambon-Thomsen, A., Mapping the translational science policy ‘valley of death.’ Clin Transl Med, 2, 2013, 14.
346. Morris, Z.S., Wooding, S., Grant, J., The answer is 17 years, what is the question: understanding time lags in translational research. J R Soc Med 104 (2011), 510–520.
347. Lenfant, C., Shattuck lecture: clinical research to clinical practice: lost in translation?. N Engl J Med 349 (2003), 868–874.
348. Grimshaw, J.M., Eccles, M.P., Lavis, J.N., Hill, S.J., Squires, J.E., Knowledge translation of research findings. Implement Sci, 7, 2012, 50.
349. McGlynn, E.A., Asch, S.M., Adams, J., et al. The quality of health care delivered to adults in the United States. N Engl J Med 348 (2003), 2635–2645.
350. Schuster, M.A., McGlynn, E.A., Brook, R.H., How good is the quality of health care in the United States? 1998. Milbank Q 83 (2005), 843–895.
351. Roberts, S.F., Fischhoff, M.A., Sakowski, S.A., Feldman, E.L., Perspective: transforming science into medicine: how clinician-scientists can build bridges across research's “valley of death”. Acad Med 87 (2012), 266–270.
352. Contopoulos-Ioannidis, D.G., Ntzani, E., Ioannidis, J.P., Translation of highly promising basic science research into clinical applications. Am J Med 114 (2003), 477–484.
353. Botting, J., The history of thalidomide. Drug News Perspect 15 (2002), 604–611.
354. Kutcher, J.S., Engle, A., Firth, J., Lamm, S.H., Bendectin and birth defects: II, ecological analyses. Birth Defects Res A Clin Mol Teratol 67 (2003), 88–97.
355. Palmer, A.K., Harris, A.L., Jacobson, R.M., Human papillomavirus vaccination: a case study in translational science. Clin Transl Sci 7 (2014), 420–424.
356. Mittendorf, R., Williams, M.A., Rho(D) immunoglobulin (RhoGAM): how it came into being. Obstet Gynecol 77 (1991), 301–303.
357. Hamilton, E.G., Rho(D) immunoglobulin (RhoGAM): how it came into being. Obstet Gynecol 77 (1991), 957–958.
358. Crowley, P., Prophylactic corticosteroids for preterm birth. Cochrane Database Syst Rev, 2000, CD000065.
359. Liggins, G.C., Premature delivery of foetal lambs infused with glucocorticoids. J Endocrinol 45 (1969), 515–523.
360. Liggins, G.C., Howie, R.N., A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics 50 (1972), 515–525.
361. American College of Obstetricians and Gynecologists. ACOG practice bulletin no. 127: management of preterm labor. Obstet Gynecol 119 (2012), 1308–1317.
362. Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consensus Development Panel on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes. JAMA 273 (1995), 413–418.
363. Bradley, E.H., Schlesinger, M., Webster, T.R., Baker, D., Inouye, S.K., Translating research into clinical practice: making change happen. J Am Geriatr Soc 52 (2004), 1875–1882.
364. Bradley, E.H., Webster, T.R., Baker, D., et al. Translating research into practice: speeding the adoption of innovative health care programs. Issue Brief (Commonw Fund) 724 (2004), 1–12.
365. Kahn, K., Ryan, G., Beckett, M., et al. Bridging the gap between basic science and clinical practice: a role for community clinicians. Implement Sci, 6, 2011, 34.
366. Green, L.A., Seifert, C.M., Translation of research into practice: why we can't “just do it”. J Am Board Fam Pract 18 (2005), 541–545.
367. National Institutes of Health, IMPACT: our economy. Available at: http://www.nih.gov/about/impact/economy.htm. Accessed: April 6, 2015.
368. Liu, G., Chen, G., Sinoway, L.I., Berg, A., Assessing the impact of the NIH CTSA program on institutionally sponsored clinical trials. Clin Transl Sci 6 (2013), 196–200.
369. The Clinical and Translational Science Award (CTSA). Available at: https://ctsacentral.org/. Accessed June 1, 2015.
370. Haas, D.M., Pharmacogenetics and individualizing drug treatment during pregnancy. Pharmacogenomics 15 (2014), 69–78.
371. Arroyo, J.D., Chevillet, J.R., Kroh, E.M., et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A 108 (2011), 5003–5008.
372. Valadi, H., Ekstrom, K., Bossios, A., Sjostrand, M., Lee, J.J., Lotvall, J.O., Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9 (2007), 654–659.
373. O'Loughlin, A.J., Woffindale, C.A., Wood, M.J., Exosomes and the emerging field of exosome-based gene therapy. Curr Gene Ther 12 (2012), 262–274.
374. Thery, C., Ostrowski, M., Segura, E., Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 9 (2009), 581–593.
375. Simons, M., Raposo, G., Exosomes: vesicular carriers for intercellular communication. Curr Opin Cell Biol 21 (2009), 575–581.
376. Raposo, G., Stoorvogel, W., Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 200 (2013), 373–383.
377. Raposo, G., Nijman, H.W., Stoorvogel, W., et al. B lymphocytes secrete antigen-presenting vesicles. J Exp Med 183 (1996), 1161–1172.
378. Akers, J.C., Gonda, D., Kim, R., Carter, B.S., Chen, C.C., Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J Neurooncol 113 (2013), 1–11.
379. Pitt, J.M., Charrier, M., Viaud, S., et al. Dendritic cell-derived exosomes as immunotherapies in the fight against cancer. J Immunol 193 (2014), 1006–1011.
380. Robbins, P.D., Morelli, A.E., Regulation of immune responses by extracellular vesicles. Nat Rev Immunol 14 (2014), 195–208.
381. Fais, S., Logozzi, M., Lugini, L., et al. Exosomes: the ideal nanovectors for biodelivery. Biol Chem 394 (2013), 1–15.
382. Tan, A., Rajadas, J., Seifalian, A.M., Exosomes as nano-theranostic delivery platforms for gene therapy. Adv Drug Deliv Rev 65 (2013), 357–367.
383. Mevorach, D., Mascarenhas, J.O., Gershov, D., Elkon, K.B., Complement-dependent clearance of apoptotic cells by human macrophages. J Exp Med 188 (1998), 2313–2320.
384. Taylor, R.C., Cullen, S.P., Martin, S.J., Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol 9 (2008), 231–241.
385. Heijnen, H.F., Schiel, A.E., Fijnheer, R., Geuze, H.J., Sixma, J.J., Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules. Blood 94 (1999), 3791–3799.
386. Cocucci, E., Racchetti, G., Meldolesi, J., Shedding microvesicles: artefacts no more. Trends Cell Biol 19 (2009), 43–51.
387. Leventis, P.A., Grinstein, S., The distribution and function of phosphatidylserine in cellular membranes. Annu Rev Biophys 39 (2010), 407–427.
388. Hugel, B., Martinez, M.C., Kunzelmann, C., Freyssinet, J.M., Membrane microparticles: two sides of the coin. Physiology (Bethesda) 20 (2005), 22–27.
389. Meckes, D.G. Jr., Raab-Traub, N., Microvesicles and viral infection. J Virol 85 (2011), 12844–12854.
390. Pols, M.S., Klumperman, J., Trafficking and function of the tetraspanin CD63. Exp Cell Res 315 (2009), 1584–1592.
391. Hemler, M.E., Tetraspanin functions and associated microdomains. Nat Rev Mol Cell Biol 6 (2005), 801–811.
392. Fomina, A.F., Deerinck, T.J., Ellisman, M.H., Cahalan, M.D., Regulation of membrane trafficking and subcellular organization of endocytic compartments revealed with FM1-43 in resting and activated human T cells. Exp Cell Res 291 (2003), 150–166.
393. Bobrie, A., Colombo, M., Raposo, G., Thery, C., Exosome secretion: molecular mechanisms and roles in immune responses. Traffic 12 (2011), 1659–1668.
394. Delorme-Axford, E., Donker, R.B., Mouillet, J.F., et al. Human placental trophoblasts confer viral resistance to recipient cells. Proc Natl Acad Sci U S A 110 (2013), 12048–12053.
395. Ouyang, Y., Mouillet, J.F., Coyne, C.B., Sadovsky, Y., Review: placenta-specific microRNAs in exosomes: good things come in nano-packages. Placenta 35:suppl (2014), S69–S73.
396. Luo, S.S., Ishibashi, O., Ishikawa, G., et al. Human villous trophoblasts express and secrete placenta-specific microRNAs into maternal circulation via exosomes. Biol Reprod 81 (2009), 717–729.
397. Donker, R.B., Mouillet, J.F., Chu, T., et al. The expression profile of C19MC microRNAs in primary human trophoblast cells and exosomes. Mol Hum Reprod 18 (2012), 417–424.
398. Aharon, A., Brenner, B., Placenta-derived microparticles. Thromb Res 131:suppl 1 (2013), S22–S24.
399. Mayhew, T.M., Turnover of human villous trophoblast in normal pregnancy: what do we know and what do we need to know?. Placenta 35 (2014), 229–240.
400. Ishihara, N., Matsuo, H., Murakoshi, H., Laoag-Fernandez, J.B., Samoto, T., Maruo, T., Increased apoptosis in the syncytiotrophoblast in human term placentas complicated by either preeclampsia or intrauterine growth retardation. Am J Obstet Gynecol 186 (2002), 158–166.
401. Salomon, C., Kobayashi, M., Ashman, K., Sobrevia, L., Mitchell, M.D., Rice, G.E., Hypoxia-induced changes in the bioactivity of cytotrophoblast-derived exosomes. PLoS One, 8, 2013, e79636.
402. Taylor, D.D., Akyol, S., Gercel-Taylor, C., Pregnancy-associated exosomes and their modulation of T cell signaling. J Immunol 176 (2006), 1534–1542.
403. Kshirsagar, S.K., Alam, S.M., Jasti, S., et al. Immunomodulatory molecules are released from the first trimester and term placenta via exosomes. Placenta 33 (2012), 982–990.
404. Sabapatha, A., Gercel-Taylor, C., Taylor, D.D., Specific isolation of placenta-derived exosomes from the circulation of pregnant women and their immunoregulatory consequences. Am J Reprod Immunol 56 (2006), 345–355.
405. Jeschke, U., Hutter, S., Heublein, S., et al. Expression and function of galectins in the endometrium and at the human feto-maternal interface. Placenta 34 (2013), 863–872.
406. Alegre, E., Rebmann, V., LemaoulT, J., et al. In vivo identification of an HLA-G complex as ubiquitinated protein circulating in exosomes. Eur J Immunol 43 (2013), 1933–1939.
407. Mincheva-Nilsson, L., Baranov, V., The role of placental exosomes in reproduction. Am J Reprod Immunol 63 (2010), 520–533.
408. Gross, J.C., Chaudhary, V., Bartscherer, K., Boutros, M., Active Wnt proteins are secreted on exosomes. Nat Cell Biol 14 (2012), 1036–1045.
409. Atay, S., Gercel-Taylor, C., Suttles, J., Mor, G., Taylor, D.D., Trophoblast-derived exosomes mediate monocyte recruitment and differentiation. Am J Reprod Immunol 65 (2011), 65–77.
410. Subra, C., Grand, D., Laulagnier, K., et al. Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins. J Lipid Res 51 (2010), 2105–2120.
411. Esser, J., Gehrmann, U., D'Alexandri, F.L., et al. Exosomes from human macrophages and dendritic cells contain enzymes for leukotriene biosynthesis and promote granulocyte migration. J Allergy Clin Immunol 126 (2010), 1032–1040.e1-4.
412. Record, M., Intercellular communication by exosomes in placenta: a possible role in cell fusion?. Placenta 35 (2014), 297–302.
413. Sarker, S., Scholz-Romero, K., Perez, A., et al. Placenta-derived exosomes continuously increase in maternal circulation over the first trimester of pregnancy. J Transl Med, 12, 2014, 204.
414. Bentwich, I., Avniel, A., Karov, Y., et al. Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet 37 (2005), 766–770.
415. Zhang, R., Wang, Y.Q., Su, B., Molecular evolution of a primate-specific microRNA family. Mol Biol Evol 25 (2008), 1493–1502.
416. Bortolin-Cavaille, M.L., Dance, M., Weber, M., Cavaille, J., C19MC microRNAs are processed from introns of large Pol-II, non-protein-coding transcripts. Nucleic Acids Res 37 (2009), 3464–3473.
417. Delorme-Axford, E., Bayer, A., Sadovsky, Y., Coyne, C.B., Autophagy as a mechanism of antiviral defense at the maternal-fetal interface. Autophagy 9 (2013), 2173–2174.
418. Bayer, A., Delorme-Axford, E., Sleigher, C., et al. Human trophoblasts confer resistance to viruses implicated in perinatal infection. Am J Obstet Gynecol 212 (2015), 71.e1–71.e8.
419. Mouillet, J.F., Ouyang, Y., Bayer, A., Coyne, C.B., Sadovsky, Y., The role of trophoblastic microRNAs in placental viral infection. Int J Dev Biol 58 (2014), 281–289.
420. Wang, K., Huang, C., Nice, E.C., Proteomics, genomics and transcriptomics: their emerging roles in the discovery and validation of colorectal cancer biomarkers. Expert Rev Proteomics 11 (2014), 179–205.
421. Choi, D.S., Kim, D.K., Kim, Y.K., Gho, Y.S., Proteomics, transcriptomics and lipidomics of exosomes and ectosomes. Proteomics 13 (2013), 1554–1571.
422. Montecalvo, A., Larregina, A.T., Shufesky, W.J., et al. Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood 119 (2012), 756–766.
423. Bartlett, D.W., Davis, M.E., Physicochemical and biological characterization of targeted, nucleic acid-containing nanoparticles. Bioconjug Chem 18 (2007), 456–468.
424. Bryniarski, K., Ptak, W., Martin, E., et al. Free extracellular miRNA functionally targets cells by transfecting exosomes from their companion cells. PLoS One, 10, 2015, e0122991.
425. Weiner, C.P., Mason, C.W., Dong, Y., Buhimschi, I.A., Swaan, P.W., Buhimschi, C.S., Human effector/initiator gene sets that regulate myometrial contractility during term and preterm labor. Am J Obstet Gynecol 202 (2010), 474.e1–474.e20.
426. Lee, J.S., Romero, R., Han, Y.M., et al. Placenta-on-a-chip: a novel platform to study the biology of the human placenta. J Matern Fetal Neonatal Med 29 (2016), 1046–1054.
427. Duncan, R., Gaspar, R., Nanomedicine(s) under the microscope. Mol Pharm 8 (2011), 2101–2141.
428. Kabanov, A.V., Polymer genomics: an insight into pharmacology and toxicology of nanomedicines. Adv Drug Deliv Rev 58 (2006), 1597–1621.
429. Rytting, E., Nguyen, J., Wang, X., Kissel, T., Biodegradable polymeric nanocarriers for pulmonary drug delivery. Expert Opin Drug Deliv 5 (2008), 629–639.
430. Peer, D., Karp, J.M., Hong, S., Farokhzad, O.C., Margalit, R., Langer, R., Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2 (2007), 751–760.
431. Rytting, E., Bur, M., Cartier, R., et al. In vitro and in vivo performance of biocompatible negatively-charged salbutamol-loaded nanoparticles. J Control Release 141 (2010), 101–107.
432. Cai, C., Bakowsky, U., Rytting, E., Schaper, A.K., Kissel, T., Charged nanoparticles as protein delivery systems: a feasibility study using lysozyme as model protein. Eur J Pharm Biopharm 69 (2008), 31–42.
433. Poulsen, M.S., Rytting, E., Mose, T., Knudsen, L.E., Modeling placental transport: correlation of in vitro BeWo cell permeability and ex vivo human placental perfusion. Toxicol In Vitro 23 (2009), 1380–1386.
434. Li, H., Van Ravenzwaay, B., Rietjens, I.M., Louisse, J., Assessment of an in vitro transport model using BeWo b30 cells to predict placental transfer of compounds. Arch Toxicol 87 (2013), 1661–1669.
435. Cartwright, L., Poulsen, M.S., Nielsen, H.M., et al. In vitro placental model optimization for nanoparticle transport studies. Int J Nanomedicine 7 (2012), 497–510.
436. Wick, P., Malek, A., Manser, P., et al. Barrier capacity of human placenta for nanosized materials. Environ Health Perspect 118 (2010), 432–436.
437. Poulsen, M.S., Mose, T., Maroun, L.L., Mathiesen, L., Knudsen, L.E., Rytting, E., Kinetics of silica nanoparticles in the human placenta. Nanotoxicology 9 (2015), 79–86.
438. Myllynen, P.K., Loughran, M.J., Howard, C.V., Sormunen, R., Walsh, A.A., Vahakangas, K.H., Kinetics of gold nanoparticles in the human placenta. Reprod Toxicol 26 (2008), 130–137.
439. Menjoge, A.R., Rinderknecht, A.L., Navath, R.S., et al. Transfer of PAMAM dendrimers across human placenta: prospects of its use as drug carrier during pregnancy. J Control Release 150 (2011), 326–338.
440. Bajoria, R., Contractor, S.F., Effect of the size of liposomes on the transfer and uptake of carboxyfluorescein by the perfused human term placenta. J Pharm Pharmacol 49 (1997), 675–681.
441. Ali, H., Kalashnikova, I., White, M.A., Sherman, M., Rytting, E., Preparation, characterization, and transport of dexamethasone-loaded polymeric nanoparticles across a human placental in vitro model. Int J Pharm 454 (2013), 149–157.
442. Yamashita, K., Yoshioka, Y., Higashisaka, K., et al. Silica and titanium dioxide nanoparticles cause pregnancy complications in mice. Nat Nanotechnol 6 (2011), 321–328.
443. Hong, J.S., Park, M.K., Kim, M.S., et al. Prenatal development toxicity study of zinc oxide nanoparticles in rats. Int J Nanomedicine 9:suppl 2 (2014), 159–171.
444. Di Bona, K.R., Xu, Y., Ramirez, P.A., et al. Surface charge and dosage dependent potential developmental toxicity and biodistribution of iron oxide nanoparticles in pregnant CD-1 mice. Reprod Toxicol 50 (2014), 36–42.
445. Tsyganova, N.A., Khairullin, R.M., Terentyuk, G.S., et al. Penetration of pegylated gold nanoparticles through rat placental barrier. Bull Exp Biol Med 157 (2014), 383–385.
446. Rattanapinyopituk, K., Shimada, A., Morita, T., et al. Demonstration of the clathrin- and caveolin-mediated endocytosis at the maternal-fetal barrier in mouse placenta after intravenous administration of gold nanoparticles. J Vet Med Sci 76 (2014), 377–387.
447. Basha, S., Vaidhyanathan, S., Pauletti, G.M., Selection of peptide ligands for human placental transcytosis systems using in vitro phage display. Methods Mol Biol 716 (2011), 141–156.
448. Wu, C.H., Liu, I.J., Lu, R.M., Wu, H.C., Advancement and applications of peptide phage display technology in biomedical science. J Biomed Sci, 23, 2016, 8.
449. Kaitu'u-lino, T.J., Pattison, S., Ye, L., et al. Targeted nanoparticle delivery of doxorubicin into placental tissues to treat ectopic pregnancies. Endocrinology 154 (2013), 911–919.
450. Rytting, E., Ahmed, M.S., Fetal drug therapy. Mattison, D.R., (eds.) Clinical pharmacology during pregnancy, 2013, Academic Press, Oxford, UK.
451. Reed, M.D., Mattison, D.R., Treating the placenta: an evolving therapeutic concept. 2013, Academic Press, Oxford, UK.
452. Khlebtsov, N., Bogatyrev, V., Dykman, L., et al. Analytical and theranostic applications of gold nanoparticles and multifunctional nanocomposites. Theranostics 3 (2013), 167–180.
453. Engelberth, S.A., Hempel, N., Bergkvist, M., Development of nanoscale approaches for ovarian cancer therapeutics and diagnostics. Crit Rev Oncog 19 (2014), 281–315.
454. Webb, J.A., Thomsen, H.S., Gadolinium contrast media during pregnancy and lactation. Acta Radiol 54 (2013), 599–600.
455. Rytting, E., Wang, X., Vernikovskaya, D.I., et al. Metabolism and disposition of bupropion in pregnant baboons (Papio cynocephalus). Drug Metab Dispos 42 (2014), 1773–1779.
456. Wang, X., Paul, J.A., Nanovskaya, T.N., Hankins, G.D., Ahmed, M.S., Quantitative determination of telavancin in pregnant baboon plasma by solid-phase extraction and LC-ESI-MS. J Pharm Biomed Anal 98 (2014), 107–112.
457. Wang, X., Abdelrahman, D.R., Fokina, V.M., Hankins, G.D., Ahmed, M.S., Nanovskaya, T.N., Metabolism of bupropion by baboon hepatic and placental microsomes. Biochem Pharmacol 82 (2011), 295–303.
458. Yan, R., Nanovskaya, T.N., Zharikova, O.L., Mattison, D.R., Hankins, G.D., Ahmed, M.S., Metabolism of 17alpha-hydroxyprogesterone caproate by hepatic and placental microsomes of human and baboons. Biochem Pharmacol 75 (2008), 1848–1857.
459. Zharikova, O.L., Ravindran, S., Nanovskaya, T.N., Hill, R.A., Hankins, G.D., Ahmed, M.S., Kinetics of glyburide metabolism by hepatic and placental microsomes of human and baboon. Biochem Pharmacol 73 (2007), 2012–2019.
460. Ravindran, S., Zharikova, O.L., Hill, R.A., Nanovskaya, T.N., Hankins, G.D., Ahmed, M.S., Identification of glyburide metabolites formed by hepatic and placental microsomes of humans and baboons. Biochem Pharmacol 72 (2006), 1730–1737.
461. Urry, D.W., Long, M.M., Cox, B.A., Ohnishi, T., Mitchell, L.W., Jacobs, M., The synthetic polypentapeptide of elastin coacervates and forms filamentous aggregates. Biochim Biophys Acta 371 (1974), 597–602.
462. Bidwell, G.L. 3rd, Raucher, D., Application of thermally responsive polypeptides directed against c-Myc transcriptional function for cancer therapy. Mol Cancer Ther 4 (2005), 1076–1085.
463. George, E.M., Liu, H., Robinson, G.G., Mahdi, F., Perkins, E., Bidwell, G.L. 3rd, Growth factor purification and delivery systems (PADS) for therapeutic angiogenesis. Vasc Cell, 7, 2015, 1.
464. Meyer, D.E., Chilkoti, A., Genetically encoded synthesis of protein-based polymers with precisely specified molecular weight and sequence by recursive directional ligation: examples from the elastin-like polypeptide system. Biomacromolecules 3 (2002), 357–367.
465. Daniell, H., Guda, C., McPherson, D.T., Zhang, X., Xu, J., Urry, D.W., Hyper expression of a synthetic protein-based polymer gene. Methods Mol Biol 63 (1997), 359–371.
466. Urry, D., Urry, C., Luan, T., et al. Temperature of polypeptide inverse temperature transition depends on mean residue hydrophobicity. J Am Chem Soc 113 (1991), 4346–4348.
467. George, E.M., Liu, H., Robinson, G.G., Bidwell, G.L., A polypeptide drug carrier for maternal delivery and prevention of fetal exposure. J Drug Target 22 (2014), 935–947.
468. Brosens, J.J., Pijnenborg, R., Brosens, I.A., The myometrial junctional zone spiral arteries in normal and abnormal pregnancies: a review of the literature. Am J Obstet Gynecol 187 (2002), 1416–1423.
469. Lyall, F., Robson, S.C., Bulmer, J.N., Spiral artery remodeling and trophoblast invasion in preeclampsia and fetal growth restriction: relationship to clinical outcome. Hypertension 62 (2013), 1046–1054.
470. Burke, S.D., Karumanchi, S.A., Spiral artery remodeling in preeclampsia revisited. Hypertension 62 (2013), 1013–1014.
471. Palei, A.C., Spradley, F.T., Warrington, J.P., George, E.M., Granger, J.P., Pathophysiology of hypertension in pre-eclampsia: a lesson in integrative physiology. Acta Physiol (Oxf) 208 (2013), 224–233.
472. Warrington, J.P., George, E.M., Palei, A.C., Spradley, F.T., Granger, J.P., Recent advances in the understanding of the pathophysiology of preeclampsia. Hypertension 62 (2013), 666–673.
473. Bidwell, G.L. 3rd, George, E.M., Maternally sequestered therapeutic polypeptides: a new approach for the management of preeclampsia. Front Pharmacol, 5, 2014, 201.
474. Maynard, S.E., Min, J.Y., Merchan, J., et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 111 (2003), 649–658.
475. Maynard, S.E., Venkatesha, S., Thadhani, R., Karumanchi, S.A., Soluble Fms-like tyrosine kinase 1 and endothelial dysfunction in the pathogenesis of preeclampsia. Pediatr Res 57 (2005), 1R–7R.
476. Sawano, A., Takahashi, T., Yamaguchi, S., Aonuma, M., Shibuya, M., Flt-1 but not KDR/Flk-1 tyrosine kinase is a receptor for placenta growth factor, which is related to vascular endothelial growth factor. Cell Growth Differ 7 (1996), 213–221.
477. Gerber, H.P., McMurtrey, A., Kowalski, J., et al. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3’-kinase/Akt signal transduction pathway: requirement for Flk-1/KDR activation. J Biol Chem 273 (1998), 30336–30343.
478. Rusterholz, C., Hahn, S., Holzgreve, W., Role of placentally produced inflammatory and regulatory cytokines in pregnancy and the etiology of preeclampsia. Semin Immunopathol 29 (2007), 151–162.
479. Kupferminc, M.J., Peaceman, A.M., Wigton, T.R., Rehnberg, K.A., Socol, M.L., Tumor necrosis factor-alpha is elevated in plasma and amniotic fluid of patients with severe preeclampsia. Am J Obstet Gynecol 170 (1994), 1752–1759.
480. Vince, G.S., Starkey, P.M., Austgulen, R., Kwiatkowski, D., Redman, C.W., Interleukin-6, tumour necrosis factor and soluble tumour necrosis factor receptors in women with pre-eclampsia. BJOG 102 (1995), 20–25.
481. Kim, Y.M., Romero, R., Oh, S.Y., et al. Toll-like receptor 4: a potential link between “danger signals,” the innate immune system, and preeclampsia?. Am J Obstet Gynecol 193 (2005), 921–927.
482. Demicheva, E., Crispi, F., Long-term follow-up of intrauterine growth restriction: cardiovascular disorders. Fetal Diagn Ther 36 (2014), 143–153.
483. Galjaard, S., Devlieger, R., Van Assche, F.A., Fetal growth and developmental programming. J Perinat Med 41 (2013), 101–105.
484. Tuovinen, S., Eriksson, J.G., Kajantie, E., Raikkonen, K., Maternal hypertensive pregnancy disorders and cognitive functioning of the offspring: a systematic review. J Am Soc Hypertens 8 (2014), 832–847.e1.