Seminal fluid signalling in the female reproductive tract: Implications for reproductive success and offspring health

Advances in Experimental Medicine and Biology

Volumn 868, Issue , 2015, Pages 127-158

  Schjenken, John E ^a   Robertson, Sarah A ^a  

^a UNIVERSITY OF ADELAIDE   (Australia)

Author keywords

Cytokines; Maternal immune tolerance; Natural killer cells; Prostaglandin E; Regulatory T cells; Seminal fluid; Toll like receptors; Transforming growth factor beta

Indexed keywords

BIRD; CONCEPTION; FEMALE GENITAL SYSTEM; FERTILIZATION; HEALTH; HUMAN; IMMUNOREGULATION; IMPLANTATION; INFERTILITY THERAPY; INNATE IMMUNITY; INVERTEBRATE; MAMMAL; MATERNAL CARE; MATING SUCCESS; MOLECULAR BIOLOGY; NIDATION; NONHUMAN; OVULATION; PIG; PREGNANCY; PRIORITY JOURNAL; PROGENY; REPRODUCTION; SEMINAL PLASMA; SEMINAL VESICLE; SIGNAL TRANSDUCTION; ANIMAL; FEMALE; MALE; METABOLISM; SPERM;

ANIMALS; FEMALE; HUMANS; MALE; REPRODUCTION; SEMEN; SIGNAL TRANSDUCTION;

EID: 84945354759     PISSN: 00652598     EISSN: 22148019     Source Type: Book Series    
DOI: 10.1007/978-3-319-18881-2_6     Document Type: Chapter

References (213)

1. Alexander NJ, Anderson DJ (1987) Immunology of semen. Fertil Steril 47:192-204
2. Aluvihare VR, Kallikourdis M, Betz AG (2004) Regulatory T cells mediate maternal tolerance to the fetus. Nat Immunol 5:266-271
3. Aplin JD (1997) Adhesion molecules in implantation. Rev Reprod 2:84-93
4. Aplin JD (2002) Endometrial extracellular matrix. In: Glasser SR, Aplin J, Guidice LC, Tabibzadeh S (eds) The endometrium. Taylor and Francis, London and New York, pp 294-307
5. Arruvito L, Sanz M, Banham AH, Fainboim L (2007) Expansion of CD4 + CD25 + and FOXP3+regulatory T cells during the follicular phase of the menstrual cycle: implications for human reproduction. J Immunol 178:2572-2578
6. Aumuller G, Riva A (1992) Morphology and functions of the human seminal vesicle. Andrologia 24:183-196
7. Bandala-Sanchez E, Zhang Y, Reinwald S, Dromey JA, Lee BH, Qian J, Bohmer RM, Harrison LC (2013) T cell regulation mediated by interaction of soluble CD52 with the inhibitory receptor Siglec-10. Nat Immunol 14:741-748
8. Baratelli F, Lin Y, Zhu L, Yang S-C, Heuze-Vourc'h N, Zeng G, Reckamp K, Dohadwala M, Sharma S, Dubinett SM (2005) Prostaglandin E2 induces FOXP3 gene expression and T regulatory cell function in human CD4+ T cells. J Immunol 175:1483-1490
9. Barker DJ, Clark PM (1997) Fetal undernutrition and disease in later life. Rev Reprod 2:105-112
10. Battersby S, Sales KJ, Williams AR, Anderson RA, Gardner S, Jabbour HN (2007) Seminal plasma and prostaglandin E2 up-regulate fi broblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway. Hum Reprod 22:36-44
11. Blois SM, Kammerer U, Alba Soto C, Tometten MC, Shaikly V, Barrientos G, Jurd R, Rukavina D, Thomson AW, Klapp BF, Fernandez N, Arck PC (2007) Dendritic cells: key to fetal tolerance? Biol Reprod 77:590-598
12. Bogle OA, Ratto MH, Adams GP (2011) Evidence for the conservation of biological activity of ovulation-inducing factor in seminal plasma. Reproduction 142:277-283
13. Bollwein H, Sowade C, Stolla R (2003) The effect of semen extender, seminal plasma and raw semen on uterine and ovarian blood fl ow in mares. Theriogenology 60:607-616
14. Brandon CI, Heusner GL, Caudle AB, Fayrer-Hosken RA (1999) Two-dimensional polyacrylamide gel electrophoresis of equine seminal plasma proteins and their correlation with fertility. Theriogenology 52:863-873
15. Brannstrom M, Mayrhofer G, Robertson SA (1993) Localization of leukocyte subsets in the rat ovary during the periovulatory period. Biol Reprod 48:277-286
16. Brannstrom M, Giesecke L, Moore IC, van den Heuvel CJ, Robertson SA (1994a) Leukocyte subpopulations in the rat corpus luteum during pregnancy and pseudopregnancy. Biol Reprod 50:1161-1167
17. Brannstrom M, Pascoe V, Norman RJ, McClure N (1994b) Localization of leukocyte subsets in the follicle wall and in the corpus luteum throughout the human menstrual cycle. Fertil Steril 61:488-495
18. Breed WG, Leigh CM, Bennett JH (1989) Sperm morphology and storage in the female reproductive tract of the fat-tailed dunnart, Sminthopsis crassicaudata (Marsupialia: Dasyuridae). Gamete Res 23:61-75
19. Bromfi eld JJ, Schjenken JE, Chin PY, Care AS, Jasper MJ, Robertson SA (2014) Maternal tract factors contribute to paternal seminal fluid impact on metabolic phenotype in offspring. Proc Natl Acad Sci USA 111:2200-2205
20. Bulletti C, De Ziegler D, Giacomucci E, Polli V, Rossi S, Alfi eri S, Flamigni C (1997) Vaginal drug delivery: the fi rst uterine pass effect. Ann N Y Acad Sci 828:285-290
21. Caballero I, Vazquez JM, Garcia EM, Roca J, Martinez EA, Calvete JJ, Sanz L, Ekwall H, Rodriguez-Martinez H (2006) Immunolocalization and possible functional role of PSP-I/PSP-II heterodimer in highly extended boar spermatozoa. J Androl 27:766-773
22. Caramalho I, Lopes-Carvalho T, Ostler D, Zelenay S, Haury M, Demengeot J (2003) Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide. J Exp Med 197:403-411
23. Care AS, Diener KR, Jasper MJ, Brown HM, Ingman WV, Robertson SA (2013) Macrophages regulate corpus luteum development during embryo implantation in mice. J Clin Invest 123:3472-3487
24. Carp HJ, Serr DM, Mashiach S, Nebel L (1984) Infl uence of insemination on the implantation of transferred rat blastocysts. Gynecol Obstet Invest 18:194-198
25. Ceelen M, van Weissenbruch MM, Roos JC, Vermeiden JP, van Leeuwen FE, Delemarre-van de Waal HA (2007) Body composition in children and adolescents born after in vitro fertilization or spontaneous conception. J Clin Endocrinol Metab 92:3417-3423
26. Ceelen M, van Weissenbruch MM, Vermeiden JP, van Leeuwen FE, Delemarrevan de Waal HA (2008) Cardiometabolic differences in children born after in vitro fertilization: follow-up study. J Clin Endocrinol Metab 93:1682-1688
27. Chan OC, Chow PH, O WS (2001) Total ablation of paternal accessory sex glands curtails developmental potential in preimplantation embryos in the golden hamster. Anat Embryol (Berl) 204:117-122
28. Chapman T, Davies SJ (2004) Functions and analysis of the seminal fluid proteins of male Drosophila melanogaster fruit fl ies. Peptides 25:1477-1490
29. Chapman T, Neubaum DM, Wolfner MF, Partridge L (2000) The role of male accessory gland protein Acp36DE in sperm competition in Drosophila melanogaster. Proc Biol Sci 267:1097-1105
30. Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM (2003) Conversion of peripheral CD4+CD25-naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198:1875-1886
31. Chin PY, Macpherson AM, Thompson JG, Lane M, Robertson SA (2009) Stress response genes are suppressed in mouse preimplantation embryos by granulocyte-macrophage colonystimulating factor (GM-CSF). Hum Reprod 24:2997-3009
32. Chow PH, Jiang HY, Poon HK, Lee KH, O WS (2003) Embryos sired by males without accessory sex glands induce failure of uterine support: a study of VEGF, MMP and TGF expression in the golden hamster. Anat Embryol 206:203-213
33. Chu TM, Nocera MA, Flanders KC, Kawinski E (1996) Localization of seminal plasma transforming growth factor-beta1 on human spermatozoa: an immunocytochemical study. Fertil Steril 66:327-330
34. Clark DA, Fernandes J, Banwatt D (2008) Prevention of spontaneous abortion in the CBA x DBA/2 mouse model by intravaginal TGF-beta and local recruitment of CD4+8+ FOXP3+ cells. Am J Reprod Immunol 59:525-534
35. Claus R (1990) Physiological role of seminal components in the reproductive tract of the female pig. J Reprod Fertil Suppl 40:117-131
36. Claus R, Dimmick MA, Gimenez T, Hudson LW (1992) Estrogens and prostaglandin F2alpha in the semen and blood plasma of stallions. Theriogenology 38:687-693
37. Cohen PE, Hardy MP, Pollard JW (1997a) Colony-stimulating factor-1 plays a major role in the development of reproductive function in male mice. Mol Endocrinol 11:1636-1650
38. Cohen PE, Zhu L, Pollard JW (1997b) Absence of colony stimulating factor-1 in osteopetrotic (csfmop/csfmop) mice disrupts estrous cycles and ovulation. Biol Reprod 56:110-118
39. Conroy H, Marshall NA, Mills KH (2008) TLR ligand suppression or enhancement of Treg cells? A double-edged sword in immunity to tumours. Oncogene 27:168-180
40. Das SK, Yano S, Wang J, Edwards DR, Nagase H, Dey SK (1997) Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in the mouse uterus during the periimplantation period. Dev Genet 21:44-54
41. Das SC, Isobe N, Yoshimura Y (2008) Mechanism of prolonged sperm storage and sperm survivability in hen oviduct: a review. Am J Reprod Immunol 60:477-481
42. Das SC, Isobe N, Yoshimura Y (2009) Changes in the expression of interleukin-1beta and lipopolysaccharide-induced TNF factor in the oviduct of laying hens in response to artifi cial insemination. Reproduction 137:527-536
43. De M, Choudhuri R, Wood GW (1991) Determination of the number and distribution of macrophages, lymphocytes, and granulocytes in the mouse uterus from mating through implantation. J Leukoc Biol 50:252-262
44. Dean MD (2013) Genetic disruption of the copulatory plug in mice leads to severely reduced fertility. PLoS Genet 9:e1003185
45. Denison FC, Grant VE, Calder AA, Kelly RW (1999) Seminal plasma components stimulate interleukin-8 and interleukin-10 release. Mol Hum Reprod 5:220-226
46. Donato R, Cannon BR, Sorci G, Riuzzi F, Hsu K, Weber DJ, Geczy CL (2013) Functions of S100 proteins. Curr Mol Med 13:24-57
47. Doty A, Buhi WC, Benson S, Scoggin KE, Pozor M, Macpherson M, Mutz M, Troedsson MH (2011) Equine CRISP3 modulates interaction between spermatozoa and polymorphonuclear neutrophils. Biol Reprod 85:157-164
48. Eberhard WG (2009) Postcopulatory sexual selection: Darwin’s omission and its consequences. Proc Natl Acad Sci USA 106(Suppl 1):10025-10032
49. England GC, Russo M, Freeman SL (2012) The bitch uterine response to semen deposition and its modifi cation by male accessory gland secretions. Vet J 195:179-84
50. Fabian D, Juhas S, Il'kova G, Koppel J (2007) Dose-and time-dependent effects of TNFalpha and actinomycin D on cell death incidence and embryo growth in mouse blastocysts. Zygote 15:241-249
51. Fallarino F, Pallotta MT, Matino D, Gargaro M, Orabona C, Vacca C, Mondanelli G, Allegrucci M, Boon L, Romani R, Talesa VN, Puccetti P et al (2015) LPS-conditioned dendritic cells confer endotoxin tolerance contingent on tryptophan catabolism. Immunobiology 220:315-21
52. Feng J, Woessner JF Jr, Zhu C (1998) Matrilysin activity in the rat uterus during the oestrous cycle and implantation. J Reprod Fertil 114:347-350
53. Flowers WL, Esbenshade KL (1993) Optimizing management of natural and artifi cial matings in swine. J Reprod Fertil Suppl 48:217-228
54. Fullston T, Palmer NO, Owens JA, Mitchell M, Bakos HW, Lane M (2012) Diet-induced paternal obesity in the absence of diabetes diminishes the reproductive health of two subsequent generations of mice. Hum Reprod 27:1391-1400
55. Gangnuss S, Sutton-McDowall ML, Robertson SA, Armstrong DT (2004) Seminal plasma regulates corpora lutea macrophage populations during early pregnancy in mice. Biol Reprod 71:1135-1141
56. Geipel U, Kropf J, Krause W, Gressner AM (1992) The concentration pattern of laminin, hyaluronan, and aminoterminal propeptide of type III procollagen in seminal fluid. Andrologia 24:205-211
57. Gillott C (2003) Male accessory gland secretions: modulators of female reproductive physiology and behavior. Annu Rev Entomol 48:163-184
58. Glynn DJ, Sharkey DJ, Robertson SA (2004) Interferon-gamma inhibits female reproductive tract responsiveness to seminal plasma, 37th Annual Meeting of the Society for the Study of Reproduction. Biol Reprod 70:242
59. Godfrey KM, Gluckman PD, Hanson MA (2010) Developmental origins of metabolic disease: life course and intergenerational perspectives. Trends Endocrinol Metab 21:199-205
60. Gopichandran N, Ekbote UV, Walker JJ, Brooke D, Orsi NM (2006) Multiplex determination of murine seminal fluid cytokine profi les. Reproduction 131:613-621
61. Guerin LR, Moldenhauer LM, Prins JR, Bromfi eld JJ, Hayball JD, Robertson SA (2011) Seminal fluid regulates accumulation of FOXP3(+) regulatory T cells in the preimplantation mouse uterus through expanding the FOXP3(+) cell pool and CCL19-mediated recruitment. Biol Reprod 85:397-408
62. Gutsche S, von Wolff M, Strowitzki T, Thaler CJ (2003) Seminal plasma induces mRNA expression of IL-1beta, IL-6 and LIF in endometrial epithelial cells in vitro. Mol Hum Reprod 9:785-791
63. Haimovici F, Hill JA, Anderson DJ (1988) Variables affecting toxicity of human sera in mouse embryo cultures. J In Vitro Fert Embryo Transf 5:202-206
64. Hanson MA, Gluckman PD (2005) Developmental processes and the induction of cardiovascular function: conceptual aspects. J Physiol 565:27-34
65. Hart R, Norman RJ (2013) The longer-term health outcomes for children born as a result of IVF treatment: part I-general health outcomes. Hum Reprod Update 19:232-243
66. Heifetz Y, Lung O, Frongillo EA Jr, Wolfner MF (2000) The Drosophila seminal fluid protein Acp26Aa stimulates release of oocytes by the ovary. Curr Biol 10:99-102
67. Hellberg P, Thomsen P, Janson PO, Brannstrom M (1991) Leukocyte supplementation increases the luteinizing hormone-induced ovulation rate in the in vitro-perfused rat ovary. Biol Reprod 44:791-797
68. Higgins SC, Lavelle EC, McCann C, Keogh B, McNeela E, Byrne P, O’Gorman B, Jarnicki A, McGuirk P, Mills KH (2003) Toll-like receptor 4-mediated innate IL-10 activates antigenspecifi c regulatory T cells and confers resistance to Bordetella pertussis by inhibiting infl ammatory pathology. J Immunol 171:3119-3127
69. Hutter H, Dohr G (1998) HLA expression on immature and mature human germ cells. J Reprod Immunol 38:101-122
70. Ideta A, Sakai S, Nakamura Y, Urakawa M, Hayama K, Tsuchiya K, Fujiwara H, Aoyagi Y (2010) Administration of peripheral blood mononuclear cells into the uterine horn to improve pregnancy rate following bovine embryo transfer. Anim Reprod Sci 117:18-23
71. Ignotz GG, Lo MC, Perez CL, Gwathmey TM, Suarez SS (2001) Characterization of a fucosebinding protein from bull sperm and seminal plasma that may be responsible for formation of the oviductal sperm reservoir. Biol Reprod 64:1806-1811
72. Jaiswal MK, Mallers TM, Larsen B, Kwak-Kim J, Chaouat G, Gilman-Sachs A, Beaman KD (2012) V-ATPase upregulation during early pregnancy: a possible link to establishment of an infl ammatory response during preimplantation period of pregnancy. Reproduction 143: 713-725
73. James K, Hargreave TB (1984) Immunosuppression by seminal plasma and its possible clinical signifi cance. Immunol Today 5:357-363
74. Jasper MJ, Robertson SA, Van der Hoek KH, Bonello N, Brannstrom M, Norman RJ (2000) Characterization of ovarian function in granulocyte-macrophage colony-stimulating factordefi cient mice. Biol Reprod 62:704-713
75. Jasper MJ, Bromfield JJ, Skinner R, Robertson SA (2005) 242. LIF expression is induced in the mouse oviduct following activation by seminal factors. Reprod Fertil Dev 17:96-96
76. Jasper MJ, Tremellen KP, Robertson SA (2006) Primary unexplained infertility is associated with reduced expression of the T-regulatory cell transcription factor Foxp3 in endometrial tissue. Mol Hum Reprod 12:301-308
77. Jasper MJ, Care AS, Sullivan B, Ingman WV, Aplin JD, Robertson SA (2011) Macrophage-derived LIF and IL1B regulate alpha(1,2)fucosyltransferase 2 (Fut2) expression in mouse uterine epithelial cells during early pregnancy. Biol Reprod 84:179-188
78. Jiang HY, O WS, Lee KH, Tang PL, Chow PH (2001) Ablation of paternal accessory sex glands is detrimental to embryo development during implantation. Anat Embryol (Berl) 203:255-263
79. Johansson M, Bromfi eld JJ, Jasper MJ, Robertson SA (2004) Semen activates the female immune response during early pregnancy in mice. Immunology 112:290-300
80. Katila T (2012) Post-mating infl ammatory responses of the uterus. Reprod Domest Anim 47(Suppl 5): 31-41
81. Kawano N, Araki N, Yoshida K, Hibino T, Ohnami N, Makino M, Kanai S, Hasuwa H, Yoshida M, Miyado K, Umezawa A (2014) Seminal vesicle protein SVS2 is required for sperm survival in the uterus. Proc Natl Acad Sci USA 111:4145-4150
82. Killian GJ, Chapman DA, Rogowski LA (1993) Fertility-associated proteins in Holstein bull seminal plasma. Biol Reprod 49:1202-1207
83. Kirsch TM, Friedman AC, Vogel RL, Flickinger GL (1981) Macrophages in corpora lutea of mice: characterization and effects on steroid secretion. Biol Reprod 25:629-638
84. Kosaka K, Fujiwara H, Tatsumi K, Yoshioka S, Higuchi T, Sato Y, Nakayama T, Fujii S (2003) Human peripheral blood mononuclear cells enhance cell-cell interaction between human endometrial epithelial cells and BeWo-cell spheroids. Hum Reprod 18:19-25
85. Koyama K, Hasegawa A, Komori S (2009) Functional aspects of CD52 in reproduction. J Reprod Immunol 83:56-59
86. Koyanagi F, Nishiyama H (1981) Fate of spermatozoa that do not participate in fertilization in the domestic fowl. Cell Tissue Res 214:89-95
87. Krzymowski T, Stefanczyk-Krzymowska S, Koziorowski M (1989) Counter current transfer of PGF2 alpha in the mesometrial vessels as a mechanism for prevention of luteal regression in early pregnancy. Acta Physiol Pol 40:23-34
88. Kunz G, Beil D, Deininger H, Wildt L, Leyendecker G (1996) The dynamics of rapid sperm transport through the female genital tract: evidence from vaginal sonography of uterine peristalsis and hysterosalpingoscintigraphy. Hum Reprod 11:627-632
89. Lafl amme BA, Avila FW, Michalski K, Wolfner MF (2014) A Drosophila protease cascade member, seminal metalloprotease-1, is activated stepwise by male factors and requires female factors for full activity. Genetics 196:1117-1129
90. Lane M, Robker RL, Robertson SA (2014) Parenting from before conception. Science 345: 756-760
91. Lengerova A, Vojtiskova M (1966) Prolonged survival of syngenic male skin grafts in parous C57 B1 mice. Folia Biol 8:21
92. Li X, Zhao X (2004) Separation and purifi cation of ovulation-inducing factors in the seminal plasma of the Bactrian camel (Camelus bactrianus). Vet Res Commun 28:235-245
93. Lilja H, Oldbring J, Rannevik G, Laurell CB (1987) Seminal vesicle-secreted proteins and their reactions during gelation and liquefaction of human semen. J Clin Invest 80:281-285
94. Lima FS, Risco CA, Thatcher MJ, Benzaquen ME, Archbald LF, Santos JE, Thatcher WW (2009) Comparison of reproductive performance in lactating dairy cows bred by natural service or timed artifi cial insemination. J Dairy Sci 92:5456-5466
95. Liu WM, Pang RT, Chiu PC, Wong BP, Lao K, Lee KF, Yeung WS (2012) Sperm-borne microRNA-34c is required for the fi rst cleavage division in mouse. Proc Natl Acad Sci USA 109:490-494
96. Lockett NN, Scott VL, Boudreaux CE, Clay BT, Pruett SB, Ryan PL, Coats KS (2010) Expression of regulatory T cell (Treg) activation markers in endometrial tissues from early and late pregnancy in the feline immunodefi ciency virus (FIV)-infected cat. Placenta 31:796-802
97. Loras B, Vetele F, El Malki A, Rollet J, Soufi r JC, Benahmed M (1999) Seminal transforming growth factor-beta in normal and infertile men. Hum Reprod 14:1534-1539
98. Loureiro B, Bonilla L, Block J, Fear JM, Bonilla AQ, Hansen PJ (2009) Colony-stimulating factor 2 (CSF-2) improves development and posttransfer survival of bovine embryos produced in vitro. Endocrinology 150:5046-5054
99. Lovell JW, Getty R (1968) Fate of semen in the uterus of the sow: histologic study of endometrium during the 27 hours after natural service. Am J Vet Res 29:609-625
100. Lucy MC (2001) Reproductive loss in high-producing dairy cattle: where will it end? J Dairy Sci 84:1277-1293
101. Lung O, Wolfner MF (2001) Identifi cation and characterization of the major Drosophila melanogaster mating plug protein. Insect Biochem Mol Biol 31:543-551
102. Ma W, Tan J, Matsumoto H, Robert B, Abrahamson DR, Das SK, Dey SK (2001) Adult tissue angiogenesis: evidence for negative regulation by estrogen in the uterus. Mol Endocrinol 15:1983-1992
103. Maegawa M, Kamada M, Irahara M, Yamamoto S, Yoshikawa S, Kasai Y, Ohmoto Y, Gima H, Thaler CJ, Aono T (2002) A repertoire of cytokines in human seminal plasma. J Reprod Immunol 54:33-42
104. Maher ER, Afnan M, Barratt CL (2003) Epigenetic risks related to assisted reproductive technologies: epigenetics, imprinting, ART and icebergs? Hum Reprod 18:2508-2511
105. Mann T (1964) The biochemistry of semen and the male reproductive tract. Wiley, New York
106. Mattner PE (1968) The distribution of spermatozoa and leucocytes in the female genital tract in goats and cattle. J Reprod Fertil 17:253-261
107. McDonald LE, Black WG, McNutt SH, Casida LE (1952) The response of the rabbit uterus to instillation of semen at different phases of the estrous cycle. Am J Vet Res 13:419-424
108. McGraw LA, Suarez SS, Wolfner MF (2015) On a matter of seminal importance. Bioessays 37:142-147
109. McMaster M, Newton R, Dey S, Andrews G (1992) Activation and distribution of infl ammatory cells in the mouse uterus during the preimplantation period. J Immunol 148:1699-1705
110. Mitchell MH, Swanson RJ, Oehninger S (2002) In vivo effect of leukemia inhibitory factor (LIF) and an anti-LIF polyclonal antibody on murine embryo and fetal development following exposure at the time of transcervical blastocyst transfer. Biol Reprod 67:460-464
111. Moldenhauer LM, Diener KR, Thring DM, Brown MP, Hayball JD, Robertson SA (2009) Crosspresentation of male seminal fluid antigens elicits T cell activation to initiate the female immune response to pregnancy. J Immunol 182:8080-8093
112. Muller M, Sales KJ, Katz AA, Jabbour HN (2006) Seminal plasma promotes the expression of tumorigenic and angiogenic genes in cervical adenocarcinoma cells via the E-series prostanoid 4 receptor. Endocrinology 147:3356-3365
113. Murakami M, Nishida T, Shiromoto M, Iwanaga S (1985) Phagocytosis of spermatozoa and latex beads by the epithelial cell of the cat oviduct: combined SEM and TEM study. Arch Histol Jpn 48:519-526
114. Murray FA, Grifo P, Parker CF (1983) Increased litter size in gilts by intrauterine infusion of seminal and sperm antigens before mating. J Anim Sci 56:895-900
115. Murray FA, Grifo P, Parker CF (1986) Increased litter size in gilts by presensitization with boar semen. J Anim Sci 196(Suppl):189
116. Narciandi F, Lloyd A, Meade KG, O’Farrelly C (2014) A novel subclass of bovine β-defensins links reproduction and immunology. Reprod Fertil Dev 26:769-77
117. Nelson SE, McLean MP, Jayatilak PG, Gibori G (1992) Isolation, characterization, and culture of cell subpopulations forming the pregnant rat corpus luteum. Endocrinology 130:954-966
118. Nogueira KD, Araujo VA, Rodrigues Sartori SS, Neves CA (2011) Phagocytosis of spermatozoa by epithelial cells in the vagina of the lizard Hemidactylus mabouia (Reptilia, Squamata). Micron 42:377-80
119. O WS, Chen HQ, Chow PH (1988) Effects of male accessory sex gland secretions on early embryonic development in the golden hamster. J Reprod Fertil 84:341-344
120. O’Leary S, Robertson SA, Armstrong DT (2001) Seminal plasma treatment stimulates progesterone synthesis during early pregnancy in the pig. In: Proceedings of the 32nd annual conference of the society for reproductive biology, Gold Coast, QLD
121. O’Leary S, Robertson SA, Armstrong DT (2002) The infl uence of seminal plasma on ovarian function in pigs—a novel infl ammatory mechanism? J Reprod Immunol 57:225-238
122. O’Leary S, Armstrong DT, Robertson SA (2011) Transforming growth factor-beta (TGFbeta) in porcine seminal plasma. Reprod Fertil Dev 23:748-758
123. O’Leary S, Jasper MJ, Warnes GM, Armstrong DT, Robertson SA (2004) Seminal plasma regulates endometrial cytokine expression, leukocyte recruitment and embryo development in the pig. Reproduction 128:237-247
124. Owen DH, Katz DF (2005) A review of the physical and chemical properties of human semen and the formulation of a semen simulant. J Androl 26:459-469
125. Pacey AA, Hill CJ, Scudamore IW, Warren MA, Barratt CL, Cooke ID (1995) The interaction in vitro of human spermatozoa with epithelial cells from the human uterine (fallopian) tube. Hum Reprod 10:360-366
126. Palm F, Walter I, Budik S, Kolodziejek J, Nowotny N, Aurich C (2008) Infl uence of different semen extenders and seminal plasma on PMN migration and on expression of IL-1beta, IL-6, TNF-alpha and COX-2 mRNA in the equine endometrium. Theriogenology 70:843-851
127. Pampfer S, Arceci RJ, Pollard JW (1991) Role of colony stimulating factor-1 (CSF-1) and other lympho-hematopoietic growth factors in mouse pre-implantation development. Bioessays 13:535-540
128. Pandya IJ, Cohen J (1985) The leukocytic reaction of the human uterine cervix to spermatozoa. Fertil Steril 43:417-421
129. Pang SF, Chow PH, Wong TM (1979) The role of the seminal vesicle, coagulating glands and prostate glands on the fertility and fecundity of mice. J Reprod Fertil 56:129-132
130. Peitz B, Olds CP (1986) Effects of seminal vesicle removal on fertility and uterine sperm motility in the house mouse. Biol Reprod 35:608-617
131. Peng J, Zipperlen P, Kubli E (2005) Drosophila sex-peptide stimulates female innate immune system after mating via the Toll and Imd pathways. Curr Biol 15:1690-1694
132. Pilch B, Mann M (2006) Large-scale and high-confi dence proteomic analysis of human seminal plasma. Genome Biol 7:R40
133. Plaks V, Birnberg T, Berkutzki T, Sela S, BenYashar A, Kalchenko V, Mor G, Keshet E, Dekel N, Neeman M, Jung S (2008) Uterine DCs are crucial for decidua formation during embryo implantation in mice. J Clin Invest 118:3954-3965
134. Politch JA, Tucker L, Bowman FP, Anderson DJ (2007) Concentrations and signifi cance of cytokines and other immunologic factors in semen of healthy fertile men. Hum Reprod 22:2928-2935
135. Pollard JW, Lin EY, Zhu L (1998) Complexity in uterine macrophage responses to cytokines in mice. Biol Reprod 58:1469-1475
136. Poon HK, Lee KH, Wong CL, O WS, Chow PH (2009) Absence of paternal accessory sex gland secretions disturbs epigenetic reprogramming and expression of Igf2 and Dlk1 in golden hamster embryos. Theriogenology 71:1367-1380
137. Pudney J, Quayle AJ, Anderson DJ (2005) Immunological microenvironments in the human vagina and cervix: mediators of cellular immunity are concentrated in the cervical transformation zone. Biol Reprod 73:1253-1263
138. Queen F, Dhabuwala CB, Pierrepoint CG (1981) The effect of removal of the various accessory sex glands on the fertility of male rats. J Reprod Fertil 62:423-436
139. Ram KR, Wolfner MF (2009) A network of interactions among seminal proteins underlies the long-term postmating response in Drosophila. Proc Natl Acad Sci USA 106:15384-15389
140. Rasmussen SJ, Eckmann L, Quayle AJ, Shen L, Zhang YX, Anderson DJ, Fierer J, Stephens RS, Kagnoff MF (1997) Secretion of proinfl ammatory cytokines by epithelial cells in response to Chlamydia infection suggests a central role for epithelial cells in chlamydial pathogenesis. J Clin Invest 99:77-87
141. Rasweiler JJ (1987) Prolonged receptivity to the male and the fate of spermatozoa in the female black mastiff bat, Molossus ater. J Reprod Fertil 79:643-654
142. Ratto M, Huanca W, Singh J, Adams GP (2006) Comparison of the effect of natural mating, LH, and GnRH on interval to ovulation and luteal function in llamas. Anim Reprod Sci 91:299-306
143. Ratto MH, Leduc YA, Valderrama XP, van Straaten KE, Delbaere LT, Pierson RA, Adams GP (2012) The nerve of ovulation-inducing factor in semen. Proc Natl Acad Sci USA 109:15042-15047
144. Rego JP, Crisp JM, Moura AA, Nouwens AS, Li Y, Venus B, Corbet NJ, Corbet DH, Burns BM, Boe-Hansen GB, McGowan MR (2014) Seminal plasma proteome of electroejaculated Bos indicus bulls. Anim Reprod Sci 148:1-17
145. Reid BL (1965) Interaction between homologous sperm and somatic cells of the uterus and peritoneum in the mouse. Exp Cell Res 40:679-683
146. Rijsselaere T, Van Soom A, Van Cruchten S, Coryn M, Gortz K, Maes D, de Kruif A (2004) Sperm distribution in the genital tract of the bitch following artifi cial insemination in relation to the time of ovulation. Reproduction 128:801-811
147. Riley JK, Heeley JM, Wyman AH, Schlichting EL, Moley KH (2004) TRAIL and KILLER are expressed and induce apoptosis in the murine preimplantation embryo. Biol Reprod 71:871-877
148. Robertson SA (2005) Seminal plasma and male factor signalling in the female reproductive tract. Cell Tissue Res 322:43-52
149. Robertson SA (2007) Seminal fluid signaling in the female reproductive tract: lessons from rodents and pigs. J Anim Sci 85:E36-44
150. Robertson SA (2010) Immune regulation of conception and embryo implantation-all about quality control? J Reprod Immunol 85:51-57
151. Robertson SA, Sharkey DJ (2001) The role of semen in induction of maternal immune tolerance to pregnancy. Semin Immunol 13:243-254
152. Robertson SA, Mayrhofer G, Seamark RF (1992) Uterine epithelial cells synthesize granulocytemacrophage colony-stimulating factor and interleukin-6 in pregnant and nonpregnant mice. Biol Reprod 46:1069-1079
153. Robertson SA, Mau VJ, Tremellen KP, Seamark RF (1996) Role of high molecular weight seminal vesicle proteins in eliciting the uterine infl ammatory response to semen in mice. J Reprod Fertil 107:265-277
154. Robertson SA, Allanson M, Mau VJ (1998) Molecular regulation of uterine leukocyte recruitment during early pregnancy in the mouse. Placenta 19:101-119
155. Robertson SA, Roberts CT, Farr KL, Dunn AR, Seamark RF (1999) Fertility impairment in granulocyte-macrophage colony-stimulating factor-defi cient mice. Biol Reprod 60:251-261
156. Robertson SA, Sjoblom C, Jasper MJ, Norman RJ, Seamark RF (2001) Granulocyte-macrophage colony-stimulating factor promotes glucose transport and blastomere viability in murine preimplantation embryos. Biol Reprod 64:1206-1215
157. Robertson SA, Ingman WV, O’Leary S, Sharkey DJ, Tremellen KP (2002) Transforming growth factor beta-a mediator of immune deviation in seminal plasma. J Reprod Immunol 57:109-128
158. Robertson SA, Guerin LR, Moldenhauer LM, Hayball JD (2009a) Activating T regulatory cells for tolerance in early pregnancy—the contribution of seminal fluid. J Reprod Immunol 83:109-116
159. Robertson SA, Guerin LR, Bromfi eld JJ, Branson KM, Ahlstrom AC, Care AS (2009b) Seminal fluid drives expansion of the CD4+CD25+ T regulatory cell pool and induces tolerance to paternal alloantigens in mice. Biol Reprod 80:1036-1045
160. Robertson SA, Chin PY, Glynn DJ, Thompson JG (2011) Peri-conceptual cytokines-setting the trajectory for embryo implantation, pregnancy and beyond. Am J Reprod Immunol 66(Suppl 1):2-10
161. Rodriguez-Martinez H, Saravia F, Wallgren M, Martinez EA, Sanz L, Roca J, Vazquez JM, Calvete JJ (2010) Spermadhesin PSP-I/PSP-II heterodimer induces migration of polymorphonuclear neutrophils into the uterine cavity of the sow. J Reprod Immunol 84:57-65
162. Roldan ER, Gomendio M, Vitullo AD (1992) The evolution of eutherian spermatozoa and underlying selective forces: female selection and sperm competition. Biol Rev Camb Philos Soc 67:551-593
163. Rozeboom KJ, Troedsson MH, Hodson HH, Shurson GC, Crabo BG (2000) The importance of seminal plasma on the fertility of subsequent artifi cial inseminations in swine. J Anim Sci 78:443-448
164. Rubtsov YP, Rudensky AY (2007) TGFbeta signalling in control of T-cell-mediated self-reactivity. Nat Rev Immunol 7:443-453
165. Rudensky AY (2011) Regulatory T, cells and Foxp3. Immunol Rev 241:260-268
166. Sakaguchi S (2000) Regulatory T, cells: key controllers of immunologic self-tolerance. Cell 101:455-458
167. Sanford TR, De M, Wood GW (1992) Expression of colony-stimulating factors and infl ammatory cytokines in the uterus of CD1 mice during days 1 to 3 of pregnancy. J Reprod Fertil 94:213-220
168. Sasaki Y, Sakai M, Miyazaki S, Higuma S, Shiozaki A, Saito S (2004) Decidual and peripheral blood CD4 + CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases. Mol Hum Reprod 10:347-353
169. Sasaki Y, Darmochwal-Kolarz D, Suzuki D, Sakai M, Ito M, Shima T, Shiozaki A, Rolinski J, Saito S (2007) Proportion of peripheral blood and decidual CD4(+) CD25(bright) regulatory T cells in pre-eclampsia. Clin Exp Immunol 149:139-145
170. Schaefer TM, Desouza K, Fahey JV, Beagley KW, Wira CR (2004) Toll-like receptor (TLR) expression and TLR-mediated cytokine/chemokine production by human uterine epithelial cells. Immunology 112:428-436
171. Schieve LA (2002) Low and very low birth weight in infants conceived with use of assisted reproductive technology. N Engl J Med 346:731
172. Schjenken J, Robertson S (2014) Seminal fluid and immune adaptation for pregnancy—comparative biology in Mammalian species. Reprod Domest Anim 49(Suppl 3):27-36
173. Schjenken SE, Glynn DJ, Sharkey DJ, Robertson SA (2015) TLR4 signaling is a major mediator of the female tract response to seminal fluid in mice. Biol Reprod (in press)
174. Scott JL, Ketheesan N, Summers PM (2006) Presence of TGFbeta but not IL-8 or GM-CSF in ram seminal plasma. Society of Reproductive Biology, Gold Coast, QLD, p 49
175. Scott JL, Ketheesan N, Summers PM (2009) Spermatozoa and seminal plasma induce a greater infl ammatory response in the ovine uterus at oestrus than dioestrus. Reprod Fertil Dev 21:817-826
176. Sharkey DJ, Macpherson AM, Tremellen KP, Robertson SA (2007) Seminal plasma differentially regulates infl ammatory cytokine gene expression in human cervical and vaginal epithelial cells. Mol Hum Reprod 13:491-501
177. Sharkey DJ, Macpherson AM, Tremellen KP, Mottershead DG, Gilchrist RB, Robertson SA (2012a) TGF-beta mediates proinfl ammatory seminal fluid signaling in human cervical epithelial cells. J Immunol 189:1024-1035
178. Sharkey DJ, Tremellen KP, Jasper MJ, Gemzell-Danielsson K, Robertson SA (2012b) Seminal fluid induces leukocyte recruitment and cytokine and chemokine mRNA expression in the human cervix after coitus. J Immunol 188:2445-2454
179. Shen XH, Han YJ, Zhang DX, Cui XS, Kim NH (2009) A link between the interleukin-6/Stat3 anti-apoptotic pathway and microRNA-21 in preimplantation mouse embryos. Mol Reprod Dev 76:854-862
180. Shevach EM (2002) CD4+ CD25+ suppressor T cells: more questions than answers. Nat Rev Immunol 2:389-400
181. Shimada M, Yanai Y, Okazaki T, Noma N, Kawashima I, Mori T, Richards JS (2008) Hyaluronan fragments generated by sperm-secreted hyaluronidase stimulate cytokine/chemokine production via the TLR2 and TLR4 pathway in cumulus cells of ovulated COCs, which may enhance fertilization. Development 135:2001-2011
182. Short SM, Wolfner MF, Lazzaro BP (2012) Female Drosophila melanogaster suffer reduced defense against infection due to seminal fluid components. J Insect Physiol 58:1192-1201
183. Sjoblom C, Wikland M, Robertson SA (1999) Granulocyte-macrophage colony-stimulating factor promotes human blastocyst development in vitro. Hum Reprod 14:3069-3076
184. Sjoblom C, Roberts CT, Wikland M, Robertson SA (2005) Granulocyte-macrophage colonystimulating factor alleviates adverse consequences of embryo culture on fetal growth trajectory and placental morphogenesis. Endocrinology 146:2142-2153
185. Skjervold H (1975) Comparison of litter size by use of natural and by artifi cial mating. Z Tierzucht Zucht Biol 92:252-259
186. Somerset DA, Zheng Y, Kilby MD, Sansom DM, Drayson MT (2004) Normal human pregnancy is associated with an elevation in the immune suppressive CD25(+) CD4(+) regulatory T-cell subset. Immunology 112:38-43
187. Suarez SS (2008) Regulation of sperm storage and movement in the mammalian oviduct. Int J Dev Biol 52:455-462
188. Suarez SS, Pacey AA (2006) Sperm transport in the female reproductive tract. Hum Reprod Update 12:23-37
189. Sutovsky P, Lovercamp K (2010) Molecular markers of sperm quality. Soc Reprod Fertil Suppl 67:247-256
190. Tanco VM, Van Steelandt MD, Ratto MH, Adams GP (2012) Effect of purifi ed llama ovulationinducing factor (OIF) on ovarian function in cattle. Theriogenology 78:1030-1039
191. Taylor U, Rath D, Zerbe H, Schuberth HJ (2008) Interaction of intact porcine spermatozoa with epithelial cells and neutrophilic granulocytes during uterine passage. Reprod Domest Anim 43:166-175
192. Templeton AA, Cooper I, Kelly RW (1978) Prostaglandin concentrations in the semen of fertile men. J Reprod Fertil 52:147-150
193. Thompson LA, Barratt CL, Bolton AE, Cooke ID (1992) The leukocytic reaction of the human uterine cervix. Am J Reprod Immunol 28:85-89
194. Thompson JG, Kind KL, Roberts CT, Robertson SA, Robinson JS (2002) Epigenetic risks related to assisted reproductive technologies: short-and long-term consequences for the health of children conceived through assisted reproduction technology: more reason for caution? Hum Reprod 17:2783-2786
195. Tomlinson MJ, White A, Barratt CL, Bolton AE, Cooke ID (1992) The removal of morphologically abnormal sperm forms by phagocytes: a positive role for seminal leukocytes? Hum Reprod 7:517-522
196. Townson DH, Warren JS, Flory CM, Naftalin DM, Keyes PL (1996) Expression of monocyte chemoattractant protein-1 in the corpus luteum of the rat. Biol Reprod 54:513-520
197. Tremellen KP, Seamark RF, Robertson SA (1998) Seminal transforming growth factor beta1 stimulates granulocyte-macrophage colony-stimulating factor production and infl ammatory cell recruitment in the murine uterus. Biol Reprod 58:1217-1225
198. Tremellen KP, Valbuena D, Landeras J, Ballesteros A, Martinez J, Mendoza S, Norman RJ, Robertson SA, Simon C (2000) The effect of intercourse on pregnancy rates during assisted human reproduction. Hum Reprod 15:2653-2658
199. Troedsson MH, Loset K, Alghamdi AM, Dahms B, Crabo BG (2001) Interaction between equine semen and the endometrium: the infl ammatory response to semen. Anim Reprod Sci 68:273-278
200. Trowsdale J, Betz AG (2006) Mother’s little helpers: mechanisms of maternal-fetal tolerance. Nat Immunol 7:241-246
201. Turner EC, Hughes J, Wilson H, Clay M, Mylonas KJ, Kipari T, Duncan WC, Fraser HM (2011) Conditional ablation of macrophages disrupts ovarian vasculature. Reproduction 141:821-831
202. Van der Hoek KH, Maddocks S, Woodhouse CM, van Rooijen N, Robertson SA, Norman RJ (2000) Intrabursal injection of clodronate liposomes causes macrophage depletion and inhibits ovulation in the mouse ovary. Biol Reprod 62:1059-1066
203. Vazquez JM, Martinez EA, Roca J, Gil MA, Parrilla I, Cuello C, Carvajal G, Lucas X, Vazquez JL (2005) Improving the effi ciency of sperm technologies in pigs: the value of deep intrauterine insemination. Theriogenology 63:536-547
204. Waberski D, Claassen R, Hahn T, Jungblut PW, Parvizi N, Kallweit E, Weitze KF (1997) LH profi le and advancement of ovulation after transcervical infusion of seminal plasma at different stages of oestrus in gilts. J Reprod Fertil 109:29-34
205. Watson JG, Carroll J, Chaykin S (1983) Reproduction in mice: the fate of spermatozoa not involved in fertilization. Gamete Res 7:75-84
206. Wolfner MF (2002) The gifts that keep on giving: physiological functions and evolutionary dynamics of male seminal proteins in Drosophila. Heredity 88:85-93
207. Wong CL, Lee KH, Lo KM, Chan OC, Goggins W, Or WS, Chow PH (2007) Ablation of paternal accessory sex glands imparts physical and behavioural abnormalities to the progeny: an in vivo study in the golden hamster. Theriogenology 68:654-662
208. Wong CL, Chan OC, Lee KH, O WS, Chow PH (2008) Absence of paternal accessory sex glands dysregulates preimplantation embryo cell cycle and causes early oviductal-uterine transit in the golden hamster in vivo. Fertil Steril 89:1021-1024
209. Wu RJ, Van der Hoek KH, Ryan NK, Norman RJ, Robker RL (2004) Macrophage contributions to ovarian function. Hum Reprod Update 10:119-133
210. Ying Y, Chow PH (1998) O WS. Effects of male accessory sex glands on deoxyribonucleic acid synthesis in the fi rst cell cycle of golden hamster embryos. Biol Reprod 58:659-663
211. Yoshida S, Ono M, Shono T, Izumi H, Ishibashi T, Suzuki H, Kuwano M (1997) Involvement of interleukin-8, vascular endothelial growth factor, and basic fi broblast growth factor in tumor necrosis factor alpha-dependent angiogenesis. Mol Cell Biol 17:4015-4023
212. Zheng WM, Nishibori M, Isobe N, Yoshimura Y (2001) An in situ hybridization study of the effects of artifi cial insemination on the localization of cells expressing MHC class II mRNA in the chicken oviduct. Reproduction 122:581-586
213. Ziebe S, Loft A, Povlsen BB, Erb K, Agerholm I, Aasted M, Gabrielsen A, Hnida C, Zobel DP, Munding B, Bendz SH, Robertson SA (2013) A randomized clinical trial to evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in embryo culture medium for in vitro fertilization. Fertil Steril 99:1600-1609