Linkage study of embryopathy-Polygenic inheritance of diabetes-induced skeletal malformations in the rat

Reproductive Toxicology

Volumn 33, Issue 3, 2012, Pages 297-307

  Nordquist, Niklas ^a   Luthman, Holger ^b   Pettersson, Ulf ^a   Eriksson, Ulf J ^a  

^a UPPSALA UNIVERSITY   (Sweden)

^b LUND UNIVERSITY   (Sweden)

Author keywords

Congenital anomalies; Diabetes in pregnancy; Genetic predisposition; Mandible; Micro satellites; Rat; Streptozotocin; Whole genome scan

Indexed keywords

AKR1B1 GENE; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BAK1 GENE; BRCC3 GENE; CHROMOSOME 10; CHROMOSOME 14; CHROMOSOME 18; CHROMOSOME 19; CHROMOSOME 4; CONGENITAL MALFORMATION; CONTROLLED STUDY; CSF1R GENE; DIABETES MELLITUS; DISEASE PREDISPOSITION; DVL2 GENE; EMBRYOPATHY; EN2 GENE; FEMALE; FETUS OUTCOME; FOLR1 GENE; GAP43 GENE; GDF1 GENE; GENE; GENE IDENTIFICATION; GENE LOCUS; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC LINKAGE; GENETIC SUSCEPTIBILITY; GENOTYPE; GSK3B GENE; MALE; MAP1B GENE; MICROSATELLITE MARKER; MITOCHONDRIAL GENOME; NF1 GENE; NOL3 GENE; NONHUMAN; RAT; SEX DIFFERENCE; SHH GENE; SKELETON MALFORMATION; TERATOGENESIS; TGFB3 GENE; TGFBR3 GENE; TP53 GENE; VEGFA GENE;

ANIMALS; DIABETES MELLITUS; DISEASE MODELS, ANIMAL; DNA, MITOCHONDRIAL; FEMALE; FETAL DISEASES; GENOTYPE; JAW ABNORMALITIES; MALE; MULTIFACTORIAL INHERITANCE; PREGNANCY; PREGNANCY IN DIABETICS; RATS; RATS, INBRED STRAINS;

RATTUS; RODENTIA;

EID: 84859739848     PISSN: 08906238     EISSN: 18731708     Source Type: Journal    
DOI: 10.1016/j.reprotox.2011.12.009     Document Type: Article

References (113)

1. Chung C.S., Myrianthopoulos N.C. Factors affecting risks of congenital malformations. II. Effect of maternal diabetes on congenital malformations. Birth Defects 1975, 11:23-38.
2. Leslie R.D.G., Pyke D.A., John P.N., White J.M. Hemoglobin A1 in diabetic pregnancy. Lancet 1978, ii:958-959.
3. Miller E., Hare J.W., Cloherty J.P., Dunn P.J., Gleason R.E., Soeldner J.S., et al. Elevated maternal hemoglobin A1c in early pregnancy and major congenital anomalies in infants of diabetic mothers. N Engl J Med 1981, 304:1331-1334.
4. Ylinen K., Raivio K., Teramo K. Haemoglobin AIc predicts the perinatal outcome in insulin-dependent diabetic pregnancies. Br J Obstet Gynaecol 1981, 88:961-967.
5. Fuhrmann K., Reiher H., Semmler K., Glöckner E. The effect of intensified conventional insulin therapy before and during pregnancy on the malformation rate in offspring of diabetic mothers. Exp Clin Endocrinol Diabetes 1984, 83:173-177.
6. Wyman A., Pinto A.B., Sheridan R., Moley K.H. One-cell zygote transfer from diabetic to nondiabetic mouse results in congenital malformations and growth retardation in offspring. Endocrinology 2008, 149:466-469.
7. Ejdesjo A., Wentzel P., Eriksson U.J. Genetic and environmental influence on diabetic rat embryopathy. Am J Physiol Endocrinol Metab 2011, 300:E454-E467.
8. Cockroft D.L., Coppola P.T. Teratogenic effect of excess glucose on head-fold rat embryos in culture. Teratology 1977, 16:141-146.
9. Horton W.E.J., Sadler T.W. Effects of maternal diabetes on early embryogenesis, Alterations in morphogenesis produced by the ketone body B-hydroxybutyrate. Diabetes 1983, 32:610-616.
10. Wentzel P., Eriksson U.J. Insulin treatment fails to abolish the teratogenic potential of serum from diabetic rats. Eur J Endocrinol 1996, 134:459-466.
11. Eriksson U.J. Importance of genetic predisposition and maternal environment for the occurrence of congenital malformations in offspring of diabetic rats. Teratology 1988, 37:365-374.
12. Otani H., Tanaka O., Tatewaki R., Naora H., Yoneyama T. Diabetic environment and genetic predisposition as causes of congenital malformations in NOD mouse embryos. Diabetes 1991, 40:1245-1250.
13. Machado A.F., Zimmerman E.F., Hovland D.N., Weiss R., Collins M.D. Diabetic embryopathy in C57BL/6J mice. Altered fetal sex ratio and impact of the splotch allele. Diabetes 2001, 50:1193-1199.
14. Fornoni A., Striker L.J., Zheng F., Striker G.E. Reversibility of glucose-induced changes in mesangial cell extracellular matrix depends on the genetic background. Diabetes 2002, 51:499-505.
15. Cederberg J., Galli J., Luthman H., Eriksson U.J. Increased mRNA levels of Mn-SOD and catalase in embryos of diabetic rats from a malformation-resistant strain. Diabetes 2000, 49:101-107.
16. Phelan S.A., Ito M., Loeken M.R. Neural tube defects in embryos of diabetic mice: role of the Pax-3 gene and apoptosis. Diabetes 1997, 46:1189-1197.
17. Trocino R.A., Akazawa S., Takino H., Takao Y., Matsumoto K., Maeda Y., et al. Cellular-tissue localization and regulation of the Glut-1 protein in both the embryo and the visceral yolk sac from normal and experimental diabetic rats during the early postimplantation period. Endocrinology 1994, 134:869-879.
18. Li R., Thorens B., Loeken M.R. Expression of the gene encoding the high-Km glucose transporter 2 by the early postimplantation mouse embryo is essential for neural tube defects associated with diabetic embryopathy. Diabetologia 2007, 50:682-689.
19. Eriksson U.J., Borg L.A.H. Protection by free oxygen radical scavenging enzymes against glucose-induced embryonic malformations in vitro. Diabetologia 1991, 34:325-331.
20. Guerin P., El Mouatassim S., Menezo Y. Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Hum Reprod Update 2001, 7:175-189.
21. Wentzel P., Eriksson U.J. Altered gene expression in rat cranial neural crest cells exposed to a teratogenic glucose concentration in vitro-paradoxical downregulation of antioxidative defense genes. Birth Defects Res B Dev Reprod Toxicol 2011, 92:487-497.
22. Fu J., Tay S.S., Ling E.A., Dheen S.T. High glucose alters the expression of genes involved in proliferation and cell-fate specification of embryonic neural stem cells. Diabetologia 2006, 49:1027-1038.
23. Jiang B., Kumar S.D., Loh W.T., Manikandan J., Ling E.A., Tay S.S., et al. Global gene expression analysis of cranial neural tubes in embryos of diabetic mice. J Neurosci Res 2008, 86:3481-3493.
24. Reece E.A., Ji I., Wu Y.K., Zhao Z. Characterization of differential gene expression profiles in diabetic embryopathy using DNA microarray analysis. Am J Obstet Gynecol 2006, 195:1075-1080.
25. Pavlinkova G., Salbaum J.M., Kappen C. Wnt signaling in caudal dysgenesis and diabetic embryopathy. Birth Defects Res A Clin Mol Teratol 2008, 82:710-719.
26. Zhao Z. Cardiac malformations and alteration of TGFbeta signaling system in diabetic embryopathy. Birth Defects Res B Dev Reprod Toxicol 2010, 89:97-105.
27. Salbaum J.M., Kappen C. Neural tube defect genes and maternal diabetes during pregnancy. Birth Defects Res A Clin Mol Teratol 2010, 88:601-611.
28. Simán C.M., Gittenberger-De Groot A.C., Wisse B., Eriksson U.J. Malformations in offspring of diabetic rats: morphometric analysis of neural crest-derived organs and effects of maternal vitamin E treatment. Teratology 2000, 61:355-367.
29. Molin D.G., Roest P.A., Nordstrand H., Wisse L.J., Poelmann R.E., Eriksson U.J., et al. Disturbed morphogenesis of cardiac outflow tract and increased rate of aortic arch anomalies in the offspring of diabetic rats. Birth Defects Res A Clin Mol Teratol 2004, 70:927-938.
30. Eriksson UJ, den Bieman M, Prins JB, van Zutphen LFM. Differences in susceptibility for diabetes-induced malformations in separated rat colonies of common origin. 4th FELASA Symposium. Lyon, France: Fondation Marcel Mérieux; 1990. p. 53-7.
31. Lincoln S.E., Lander E.S. Systematic detection of errors in genetic linkage data. Genomics 1992, 14:604-610.
32. Pampfer S., Cordi S., Vanderheyden I., Van Der Smissen P., Courtoy P.J., Van Cauwenberge A., et al. Expression and role of Bcl-2 in rat blastocysts exposed to high D-glucose. Diabetes 2001, 50:143-149.
33. Pani L., Horal M., Loeken M.R. Rescue of neural tube defects in Pax-3-deficient embryos by p53 loss of function: implications for Pax-3- dependent development and tumorigenesis. Genes Dev 2002, 16:676-680.
34. Sun F., Akazawa S., Sugahara K., Kamihira S., Kawasaki E., Eguchi K., et al. Apoptosis in normal rat embryo tissues during early organogenesis: the possible involvement of Bax and Bcl-2. Arch Histol Cytol 2002, 65:145-157.
35. Wentzel P., Ejdesjo A., Eriksson U.J. Maternal diabetes in vivo and high glucose in vitro diminish gapdh activity in rat embryos. Diabetes 2003, 52:1222-1228.
36. Madri J.A., Enciso J., Pinter E. Maternal diabetes: effects on embryonic vascular development-a vascular endothelial growth factor-A-mediated process. Pediatr Dev Pathol 2003, 6:334-341.
37. Liao D.M., Ng Y.K., Tay S.S., Ling E.A., Dheen S.T. Altered gene expression with abnormal patterning of the telencephalon in embryos of diabetic Albino Swiss mice. Diabetologia 2004, 47:523-531.
38. Reece E.A., Ma X.D., Zhao Z., Wu Y.K., Dhanasekaran D. Aberrant patterns of cellular communication in diabetes-induced embryopathy in rats: II, apoptotic pathways. Am J Obstet Gynecol 2005, 192:967-972.
39. Wentzel P., Gareskog M., Eriksson U.J. Folic acid supplementation diminishes diabetes- and glucose-induced dysmorphogenesis in rat embryos in vivo and in vitro. Diabetes 2005, 54:546-553.
40. Gareskog M., Cederberg J., Eriksson U.J., Wentzel P. Maternal diabetes in vivo and high glucose concentration in vitro increases apoptosis in rat embryos. Reprod Toxicol 2007, 23:63-74.
41. Fu J., Tay S.S., Ling E.A., Dheen S.T. Aldose reductase is implicated in high glucose-induced oxidative stress in mouse embryonic neural stem cells. J Neurochem 2007, 103:1654-1665.
42. Kumar S.D., Dheen S.T., Tay S.S. Maternal diabetes induces congenital heart defects in mice by altering the expression of genes involved in cardiovascular development. Cardiovasc Diabetol 2007, 6:34.
43. Morgan S.C., Relaix F., Sandell L.L., Loeken M.R. Oxidative stress during diabetic pregnancy disrupts cardiac neural crest migration and causes outflow tract defects. Birth Defects Res A Clin Mol Teratol 2008, 82:453-463.
44. Sato N., Sugimura Y., Hayashi Y., Murase T., Kanou Y., Kikkawa F., et al. Identification of genes differentially expressed in mouse fetuses from streptozotocin-induced diabetic pregnancy by cDNA subtraction. Endocr J 2008, 55:317-323.
45. Wentzel P., Gareskog M., Eriksson U.J. Decreased cardiac glutathione peroxidase levels and enhanced mandibular apoptosis in malformed embryos of diabetic rats. Diabetes 2008, 57:3344-3352.
46. Reinking B.E., Wedemeyer E.W., Weiss R.M., Segar J.L., Scholz T.D. Cardiomyopathy in offspring of diabetic rats is associated with activation of the MAPK and apoptotic pathways. Cardiovasc Diabetol 2009, 8:43.
47. Kamimoto Y., Sugiyama T., Kihira T., Zhang L., Murabayashi N., Umekawa T., et al. Transgenic mice overproducing human thioredoxin-1, an antioxidative and anti-apoptotic protein, prevents diabetic embryopathy. Diabetologia 2010, 53:2046-2055.
48. Liang J., Gui Y., Wang W., Gao S., Li J., Song H. Elevated glucose induces congenital heart defects by altering the expression of tbx5, tbx20, and has2 in developing zebrafish embryos. Birth Defects Res A Clin Mol Teratol 2010, 88:480-486.
49. Cheng X., Siow R.C., Mann G.E. Impaired redox signaling and antioxidant gene expression in endothelial cells in diabetes: a role for mitochondria and the nuclear factor-E2-related factor 2-Kelch-like ECH-associated protein 1 defense pathway. Antioxid Redox Signal 2011, 14:469-488.
50. Yang P., Reece E.A. Role of HIF-1alpha in maternal hyperglycemia-induced embryonic vasculopathy. Am J Obstet Gynecol 2011.
51. Morgan S.C., Lee H.Y., Relaix F., Sandell L.L., Levorse J.M., Loeken M.R. Cardiac outflow tract septation failure in Pax3-deficient embryos is due to p53-dependent regulation of migrating cardiac neural crest. Mech Dev 2008, 125:757-767.
52. Mina M. Regulation of mandibular growth and morphogenesis. Crit Rev Oral Biol Med 2001, 12:276-300.
53. Cohen M.M. Malformations of the craniofacial region: evolutionary, embryonic, genetic, and clinical perspectives. Am J Med Genet 2002, 115:245-268.
54. Chai Y., Maxson R.E. Recent advances in craniofacial morphogenesis. Dev Dyn 2006, 235:2353-2575.
55. Chiang C., Litingtung Y., Lee E., Young K.E., Corden J.L., Westphal H., et al. Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 1996, 383:407-413.
56. Maity T., Fuse N., Beachy P.A. Molecular mechanisms of Sonic hedgehog mutant effects in holoprosencephaly. Proc Natl Acad Sci USA 2005, 102:17026-17031.
57. Roelink H., Porter J.A., Chiang C., Tanabe Y., Chang D.T., Beachy P.A., et al. Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis. Cell 1995, 81:445-455.
58. Selleck M.A., Garcia-Castro M.I., Artinger K.B., Bronner-Fraser M. Effects of Shh and Noggin on neural crest formation demonstrate that BMP is required in the neural tube but not ectoderm. Development 1998, 125:4919-4930.
59. Ahlgren S.C., Bronner-Fraser M. Inhibition of sonic hedgehog signaling in vivo results in craniofacial neural crest cell death. Curr Biol 1999, 9:1304-1314.
60. Ahlgren S.C., Thakur V., Bronner-Fraser M. Sonic hedgehog rescues cranial neural crest from cell death induced by ethanol exposure. Proc Natl Acad Sci USA 2002, 99:10476-10481.
61. Thomason H.A., Dixon M.J., Dixon J. Facial clefting in Tp63 deficient mice results from altered Bmp4, Fgf8 and Shh signaling. Dev Biol 2008, 321:273-282.
62. Ratzka A., Kalus I., Moser M., Dierks T., Mundlos S., Vortkamp A. Redundant function of the heparan sulfate 6-O-endosulfatases Sulf1 and Sulf2 during skeletal development. Dev Dyn 2008, 237:339-353.
63. Zelzer E., Mamluk R., Ferrara N., Johnson R.S., Schipani E., Olsen B.R. VEGFA is necessary for chondrocyte survival during bone development. Development 2004, 131:2161-2171.
64. Hogan K.A., Ambler C.A., Chapman D.L., Bautch V.L. The neural tube patterns vessels developmentally using the VEGF signaling pathway. Development 2004, 131:1503-1513.
65. Darland DC, Cain JT, Berosik MA, Saint-Geniez M, Odens PW, Schaubhut GJ, et al. Vascular endothelial growth factor (VEGF) isoform regulation of early forebrain development. Dev Biol 358:9-22.
66. Zabihi S., Eriksson U.J., Wentzel P. Folic acid supplementation affects ROS scavenging enzymes, enhances Vegf-A, and diminishes apoptotic state in yolk sacs of embryos of diabetic rats. Reprod Toxicol 2007, 23:486-498.
67. Juhaszova M., Zorov D.B., Yaniv Y., Nuss H.B., Wang S., Sollott S.J. Role of glycogen synthase kinase-3beta in cardioprotection. Circ Res 2009, 104:1240-1252.
68. Vasileva A.K., Plotnikov E.Y., Kazachenko A.V., Kirpatovsky V.I., Zorov D.B. Inhibition of GSK-3beta decreases the ischemia-induced death of renal cells. Bull Exp Biol Med 2010, 149:303-307.
69. Yamaguchi T.P., Bradley A., McMahon A.P., Jones S. A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development 1999, 126:1211-1223.
70. Anjaneyulu M., Berent-Spillson A., Inoue T., Choi J., Cherian K., Russell J.W. Transforming growth factor-beta induces cellular injury in experimental diabetic neuropathy. Exp Neurol 2008, 211:469-479.
71. Opperman L.A., Adab K., Gakunga P.T. Transforming growth factor-beta 2 and TGF-beta 3 regulate fetal rat cranial suture morphogenesis by regulating rates of cell proliferation and apoptosis. Dev Dyn 2000, 219:237-247.
72. Andersson O., Reissmann E., Jornvall H., Ibanez C.F. Synergistic interaction between Gdf1 and Nodal during anterior axis development. Dev Biol 2006, 293:370-381.
73. Solloway M.J., Robertson E.J. Early embryonic lethality in Bmp5;Bmp7 double mutant mice suggests functional redundancy within the 60A subgroup. Development 1999, 126:1753-1768.
74. Henkemeyer M., Rossi D.J., Holmyard D.P., Puri M.C., Mbamalu G., Harpal K., et al. Vascular system defects and neuronal apoptosis in mice lacking ras GTPase-activating protein. Nature 1995, 377:695-701.
75. Dai X.M., Ryan G.R., Hapel A.J., Dominguez M.G., Russell R.G., Kapp S., et al. Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects. Blood 2002, 99:111-120.
76. Li J., Chen K., Zhu L., Pollard J.W. Conditional deletion of the colony stimulating factor-1 receptor (c-fms proto-oncogene) in mice. Genesis 2006, 44:328-335.
77. Culmsee C., Zhu X., Yu Q.S., Chan S.L., Camandola S., Guo Z., et al. A synthetic inhibitor of p53 protects neurons against death induced by ischemic and excitotoxic insults, and amyloid beta-peptide. J Neurochem 2001, 77:220-228.
78. Yamauchi H., Katayama K., Ueno M., He X.J., Mikami T., Uetsuka K., et al. Essential role of p53 in trophoblastic apoptosis induced in the developing rodent placenta by treatment with a DNA-damaging agent. Apoptosis 2007, 12:1743-1754.
79. Tamm C., Zhivotovsky B., Ceccatelli S. Caspase-2 activation in neural stem cells undergoing oxidative stress-induced apoptosis. Apoptosis 2008, 13:354-363.
80. Menini S., Iacobini C., Oddi G., Ricci C., Simonelli P., Fallucca S., et al. Increased glomerular cell (podocyte) apoptosis in rats with streptozotocin-induced diabetes mellitus: role in the development of diabetic glomerular disease. Diabetologia 2007, 50:2591-2599.
81. Ortega-Camarillo C., Guzman-Grenfell A.M., Garcia-Macedo R., Rosales-Torres A.M., Avalos-Rodriguez A., Duran-Reyes G., et al. Hyperglycemia induces apoptosis and p53 mobilization to mitochondria in RINm5F cells. Mol Cell Biochem 2006, 281:163-171.
82. Jia D.Y., Liu H.J., Wang F.W., Liu S.M., Ling E.A., Liu K., et al. Folic acid supplementation affects apoptosis and differentiation of embryonic neural stem cells exposed to high glucose. Neurosci Lett 2008, 440:27-31.
83. Piedrahita J.A., Oetama B., Bennett G.D., van Waes J., Kamen B.A., Richardson J., et al. Mice lacking the folic acid-binding protein Folbp1 are defective in early embryonic development. Nat Genet 1999, 23:228-232.
84. Oyama K., Sugimura Y., Murase T., Uchida A., Hayasaka S., Oiso Y., et al. Folic acid prevents congenital malformations in the offspring of diabetic mice. Endocr J 2009, 56:29-37.
85. Kao Y.L., Donaghue K., Chan A., Knight J., Silink M. A novel polymorphism in the aldose reductase gene promoter region is strongly associated with diabetic retinopathy in adolescents with type 1 diabetes. Diabetes 1999, 48:1338-1340.
86. Moczulski D.K., Scott L., Antonellis A., Rogus J.J., Rich S.S., Warram J.H., et al. Aldose reductase gene polymorphisms and susceptibility to diabetic nephropathy in Type 1 diabetes mellitus. Diabet Med 2000, 17:111-118.
87. Li Q., Xie P., Huang J., Gu Y., Zeng W., Song H. Polymorphisms and functions of the aldose reductase gene 5' regulatory region in Chinese patients with type 2 diabetes mellitus. Chin Med J (Engl) 2002, 115:209-213.
88. Liu Y.F., Wat N.M., Chung S.S., Ko B.C., Lam K.S. Diabetic nephropathy is associated with the 5'-end dinucleotide repeat polymorphism of the aldose reductase gene in Chinese subjects with Type 2 diabetes. Diabet Med 2002, 19:113-118.
89. Park H.K., Ahn C.W., Lee G.T., Kim S.J., Song Y.D., Lim S.K., et al. (AC)(n) polymorphism of aldose reductase gene and diabetic microvascular complications in type 2 diabetes mellitus. Diabetes Res Clin Pract 2002, 55:151-157.
90. Meixner A., Haverkamp S., Wassle H., Fuhrer S., Thalhammer J., Kropf N., et al. MAP1B is required for axon guidance and Is involved in the development of the central and peripheral nervous system. J Cell Biol 2000, 151:1169-1178.
91. Benowitz L.I., Routtenberg A. GAP-43: an intrinsic determinant of neuronal development and plasticity. Trends Neurosci 1997, 20:84-91.
92. Zabihi S., Wentzel P., Eriksson U.J. Maternal blood glucose levels determine the severity of diabetic embryopathy in mice with different expression of copper-zinc superoxide dismutase (CuZnSOD). Toxicol Sci 2008, 105:166-172.
93. Yoh K., Hirayama A., Ishizaki K., Yamada A., Takeuchi M., Yamagishi S., et al. Hyperglycemia induces oxidative and nitrosative stress and increases renal functional impairment in Nrf2-deficient mice. Genes Cells 2008, 13:1159-1170.
94. Jiang T., Huang Z., Lin Y., Zhang Z., Fang D., Zhang D.D. The protective role of Nrf2 in streptozotocin-induced diabetic nephropathy. Diabetes 2010, 59:850-860.
95. Chartoumpekis D.V., Ziros P.G., Psyrogiannis A.I., Papavassiliou A.G., Kyriazopoulou V.E., Sykiotis G.P., et al. Nrf2 represses FGF21 during long-term high-fat diet-induced obesity in mice. Diabetes 2011, 60:2465-2473.
96. Zheng H., Whitman S.A., Wu W., Wondrak G.T., Wong P.K., Fang D., et al. Therapeutic potential of Nrf2 activators in streptozotocin-induced diabetic nephropathy. Diabetes 2011, 60:3055-3066.
97. Wuu Y.D., Pampfer S., Becquet P., Vanderheyden I., Lee K.H., De Hertogh R. Tumor necrosis factor alpha decreases the viability of mouse blastocysts in vitro and in vivo. Biol Reprod 1999, 60:479-483.
98. Pampfer S., Vanderheyden I., McCracken J.E., Vesela J., De Hertogh R. Increased cell death in rat blastocysts exposed to maternal diabetes in utero and to high glucose or tumor necrosis factor-alpha in vitro. Development 1997, 124:4827-4836.
99. Cederberg J., Eriksson U.J. Decreased catalase activity in malformation-prone embryos of diabetic rats. Teratology 1997, 56:350-357.
100. Cai J., Phelan S.A., Hill A.L., Loeken M.R. Identification of Dep-1, a new gene regulated by the transcription factor Pax-3, as a marker for altered embryonic gene expression during diabetic pregnancy. Diabetes 1998, 47:1803-1805.
101. Hill A.L., Phelan S.A., Loeken M.R. Reduced expression of Pax-3 is associated with overexpression of cdc46 in the mouse embryo. Dev Genes Evol 1998, 208:128-134.
102. Chang T.I., Loeken M.R. Genotoxicity and diabetic embryopathy: impaired expression of developmental control genes as a cause of defective morphogenesis. Semin Reprod Endocrinol 1999, 17:153-165.
103. Chang T.I., Horal M., Jain S.K., Wang F., Patel R., Loeken M.R. Oxidant regulation of gene expression and neural tube development: Insights gained from diabetic pregnancy on molecular causes of neural tube defects. Diabetologia 2003, 46:538-545.
104. Eriksson U.J. Oxidative DNA damage and embryo development (Letter). Nat. Med 1999, 5:715.
105. Loeken M.R. Free radicals and birth defects. J Matern Fetal Neonatal Med 2004, 15:6-14.
106. Hide T., Hatakeyama J., Kimura-Yoshida C., Tian E., Takeda N., Ushio Y., et al. Genetic modifiers of otocephalic phenotypes in Otx2 heterozygous mutant mice. Development 2002, 129:4347-4357.
107. Vingsbo-Lundberg C., Nordquist N., Olofsson P., Sundvall M., Saxne T., Pettersson U., et al. Genetic control of arthritis onset, severity and chronicity in a model for rheumatoid arthritis in rats. Nat Genet 1998, 20:401-404.
108. Bergsteinsdottir K., Yang H.T., Pettersson U., Holmdahl R. Evidence for common autoimmune disease genes controlling onset, severity, and chronicity based on experimental models for multiple sclerosis and rheumatoid arthritis. J Immunol 2000, 164:1564-1568.
109. Ueno T., Tremblay J., Kunes J., Zicha J., Dobesova Z., Pausova Z., et al. Gender-specific genetic determinants of blood pressure and organ weight: pharmacogenetic approach. Physiol Res 2003, 52:689-700.
110. Evers I.M., de Valk H.W., Visser G.H. Male predominance of congenital malformations in infants of women with type 1 diabetes. Diabetes Care 2009, 32:1194-1195.
111. Zhu H., Kartiko S., Finnell R.H. Importance of gene-environment interactions in the etiology of selected birth defects. Clin Genet 2009, 75:409-423.
112. Amini S.A., Dunstan R.H., Dunkley P.R., Murdoch R.N. Oxidative stress and the fetotoxicity of alcohol consumption during pregnancy. Free Radic Biol Med 1996, 21:357-365.
113. Parman T., Wiley M.J., Wells P.G. Free radical-mediated oxidative DNA damage in the mechanism of thalidomide teratogenicity. Nat Med 1999, 5:582-585.