Expression of TGF-beta superfamily growth factors, their receptors, the associated SMADs and antagonists in five isolated size-matched populations of pre-antral follicles from normal human ovaries

Molecular Human Reproduction

Volumn 20, Issue 4, 2014, Pages 293-308

  Kristensen, Stine Gry ^a   Andersen, Kasper ^a   Clement, Christian Alexandro ^b   Franks, Stephen ^c   Hardy, Kate ^c   Andersen, Claus Yding ^a  

^a University of Copenhagen   (Denmark)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

^c IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

Follicle development; Gene expression; Growth factors

Indexed keywords

BONE MORPHOGENETIC PROTEIN; BONE MORPHOGENETIC PROTEIN 12; BONE MORPHOGENETIC PROTEIN 15; BONE MORPHOGENETIC PROTEIN 2; BONE MORPHOGENETIC PROTEIN 4; BONE MORPHOGENETIC PROTEIN 5; BONE MORPHOGENETIC PROTEIN 6; BONE MORPHOGENETIC PROTEIN 9; BONE MORPHOGENETIC PROTEIN RECEPTOR 1A; BONE MORPHOGENETIC PROTEIN RECEPTOR 1B; FOLLISTATIN; GROWTH DIFFERENTIATION FACTOR 1; GROWTH DIFFERENTIATION FACTOR 10; GROWTH DIFFERENTIATION FACTOR 15; GROWTH DIFFERENTIATION FACTOR 3; GROWTH DIFFERENTIATION FACTOR 5; GROWTH DIFFERENTIATION FACTOR 6; GROWTH DIFFERENTIATION FACTOR 9; HORMONE RECEPTOR; INHIBIN A; MUELLERIAN INHIBITING FACTOR; OSTEOGENIC PROTEIN 1; OSTEOGENIN; PROCOLLAGEN C PROTEINASE; SMAD PROTEIN; SMAD3 PROTEIN; SMAD4 PROTEIN; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA RECEPTOR; TRANSFORMING GROWTH FACTOR BETA RECEPTOR 3;

ADULT; ARTICLE; CELL ISOLATION; CONTROLLED STUDY; ENZYME ISOLATION; FEMALE; FERTILITY PRESERVATION; FOLLICLE ISOLATION; GENE EXPRESSION; GENOME ANALYSIS; HUMAN; HUMAN TISSUE; IMMUNOCYTOCHEMISTRY; OVARY FOLLICLE; OVARY FOLLICLE DEVELOPMENT; POPULATION; PRECAMBRIAN; PRIORITY JOURNAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; YOUNG ADULT;

FOLLICLE DEVELOPMENT; GENE EXPRESSION; GROWTH FACTORS;

ADULT; BONE MORPHOGENETIC PROTEIN 15; BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II; FEMALE; FOLLISTATIN; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GENOME, HUMAN; GENOME-WIDE ASSOCIATION STUDY; GROWTH DIFFERENTIATION FACTOR 9; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; OVARIAN FOLLICLE; RECEPTORS, TRANSFORMING GROWTH FACTOR BETA; SIGNAL TRANSDUCTION; SMAD PROTEINS; TRANSFORMING GROWTH FACTOR BETA;

EID: 84896481675     PISSN: 13609947     EISSN: 14602407     Source Type: Journal    
DOI: 10.1093/molehr/gat089     Document Type: Article

References (126)

1. Aaltonen J, Laitinen MP, Vuojolainen K, Jaatinen R, Horelli-Kuitunen N, Seppa L, Louhio H, Tuuri T, Sjoberg J, Butzow R et al. Human growth differentiation factor 9 (GDF-9) and its novel homolog GDF-9B are expressed in oocytes during early folliculogenesis. J Clin Endocrinol Metab 1999;84:2744-2750.
2. Abir R, Ben-Haroush A, Melamed N, Felz C, Krissi H, Fisch B. Expression of bone morphogenetic proteins 4 and 7 and their receptors IA, IB, and II in human ovaries from fetuses and adults. Fertil Steril 2008;89:1430-1440.
3. Abreu JG, Ketpura NI, Reversade B, De Robertis EM. Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-b. Nat Cell Biol 2002;4:599-604.
4. Andersen CY, Rosendahl M, Byskov AG, Loft A, Ottosen C, Dueholm M, Schmidt KL, Andersen AN, Ernst E. Two successful pregnancies following autotransplantation of frozen/thawed ovarian tissue. Hum Reprod 2008;23:2266-2272.
5. AndersenCY, Schmidt KT, Kristensen SG, Rosendahl M, Byskov AG, Ernst E. Concentrations of AMH and inhibin-B in relation to follicular diameter in normal human small antral follicles. Hum Reprod 2010;25:1282-1287.
6. Anderson RA, Nelson SM,WallaceWH. Measuring anti-Müllerian hormone for the assessment of ovarian reserve: when and for whom is it indicated? Maturitas 2012;71:28-33.
7. BaarendsWM,Uilenbroek JT, Kramer P, HoogerbruggeJW, van Leeuwen EC, Themmen AP, Grootegoed JA. Anti-Mullerian hormone and anti-Mullerian hormone type II receptor messenger ribonucleic acid expression in rat ovaries during postnatal development, the estrous cycle and gonadotropininduced follicle growth. Endocrinology 1995;136:4951-4962.
8. Bodensteiner KJ, Clay CM, Moeller CL, Sawyer HR. Molecular cloning of the ovine growth/differentiation factor-9 gene and expression of growth/ differentiation factor-9 in ovine and bovine ovaries. Biol Reprod 1999;60: 381-386.
9. Carlsson IB, Scott JE, Visser JA, Ritvos O, Themmen AP, Hovatta O. Anti-Mullerian hormone inhibits initiation of growth of human primordial ovarian follicles in vitro. Hum Reprod 2006;21:2223-2227.
10. Carmillo P, Tizard R, Picard JY, Vigier B, Josso N, Cate R. Cloning, expression, and alternative splicing of the receptor for anti-Müllerian hormone. Mol Endocrinol 1994;8:1006-1020.
11. Cellière G, FengosG, Hervé M, Iber D. Plasticity of TGF-bsignaling. BMCSyst Biol 2011;5:184.
12. Chang H, Brown CW, Matzuk MM. Genetic analysis of the mammalian transforming growth factor-beta superfamily. Endocr Rev 2002a;23:787-823.
13. Chang H, Brown CW, Matzuk MM. Genetic analysis of the mammalian transforming growth factor-beta superfamily. EndocrRev2002b;23:787-823.
14. Chegini N, Flanders KC. Presence of transforming growth factor-b and their selective cellular localization in human ovarian tissue of various reproductive stages. Endocrinology 1992;130:1707-1715.
15. Coccia ME, Rizzello F. Ovarian reserve. Ann N Y Acad Sci 2008;1127:27-30.
16. CookRW, Thompson TB, Jardetzky TS,Woodruff TK. Molecular biology of inhibin action. Semin Reprod Med 2004;22:269-276.
17. Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 2003;9:577-584.
18. Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, Matzuk MM. Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 1996;383:531-535.
19. Drummond AE, Dyson M, Thean E, Groome NP, Robertson DM, Findlay JK. Temporal and hormonal regulation of inhibin protein and subunit mRNA expression by post-natal and immature rat ovaries. J Endocrinol 2000; 166:339-354.
20. Drummond AE, Le MT, Ethier JF, Dyson M, Findlay JK. Expression and localization of activin receptors, Smads, and beta glycan to the postnatal rat ovary. Endocrinology 2002;143:1423-1433.
21. Dube JL, Wang P, Elvin J, Lyons KM, Celeste AJ, Matzuk MM. The bone morphogenetic protein 15 gene is X-linked and expressed in oocytes. Mol Endocrinol 1998;12:1809-1817.
22. Durlinger AL, Kramer P, Karels B, de Jong FH, Uilenbroek JT, Grootegoed JA, Themmen AP. Control of primordial follicle recruitment by anti-Mullerian hormone in the mouse ovary. Endocrinology 1999;140:5789-5796.
23. Durlinger AL, Gruijters MJ, Kramer P, Karels B, Ingraham HA, NachtigalMW, Uilenbroek JT, Grootegoed JA, Themmen AP. Anti-Mullerian hormone inhibits initiation of primordial follicle growth in the mouse ovary. Endocrinology 2002;143:1076-1084.
24. Durlinger AL, Visser JA, Themmen AP. Regulation of ovarian function: the role of anti-Mullerian hormone. Reproduction 2002a;124:601-609.
25. Durlinger AL, Gruijters MJ, Kramer P, Karels B, Ingraham HA, NachtigalMW, Uilenbroek JT, Grootegoed JA, Themmen AP. Anti-Mullerian hormone inhibits initiation of primordial follicle growth in the mouse ovary. Endocrinology 2002b;143:1076-1084.
26. Eckery DC, Whale LJ, Lawrence SB, Wylde KA, McNatty KP, Juengel JL. Expression of mRNA encoding growth differentiation factor 9 and bone morphogenetic protein 15 during follicular formation and growth in a marsupial, the brushtail possum (Trichosurus vulpecula). Mol Cell Endocrinol 2002;192:115-126.
27. Edson MA, Nagaraja AK, Matzuk MM. The mammalian ovary from genesis to revelation. Endocr Rev 2009;30:624-712.
28. Edwards SJ, Reader KL, Lun S, Western A, Lawrence S, McNatty KP, Juengel JL. The cooperative effect of growth and differentiation factor-9 and bone morphogenetic protein (BMP)-15 on granulosa cell function is modulated primarily through BMP receptor II. Endocrinology 2008;149:1026-1030.
29. Elvin JA, Yan C, Matzuk MM. Oocyte-expressed TGF-b superfamily members in female fertility. Mol Cell Endocrinol 2000;159:1-5.
30. Eppig JJ. Oocyte control of ovarian follicular development and function in mammals. Reproduction 2001;122:829-838.
31. EricksonGF, Shimasaki S. The spatiotemporal expression pattern of the bone morphogenetic protein family in rat ovary cell types during the estrous cycle. Reprod Biol Endocrinol 2003;5:1-9.
32. Fenwick MA, Mansour YT, Franks S, Hardy K. Identification and regulation of bone morphogenetic protein antagonists associated with pre-antral follicle development in the ovary. Endocrinology 2011;152:3515-3526.
33. Galloway SM, McNatty KP, Cambridge LM, Laitinen MP, Juengel JL, Jokiranta TS, McLaren RJ, Luiro K, Dodds KG, Montgomery GW et al. Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nat Genet 2000;25:279-283.
34. Gilchrist RB, Ritter LJ, Myllymaa S, Kaivo-Oja N, Dragovic RA, Hickey TE, Ritvos O, Mottershead DG. Molecular basis of oocyte-paracrine signalling that promotes granulosa cell proliferation. J. Cell Sci 2006a; 119:3811-3821.
35. Gilchrist RB, Ritter LJ, Myllymaa S, Kaivo-Oja N, Dragovic RA, Hickey TE, Ritvos O, Mottershead DG. Molecular basis of oocyte-paracrine signalling that promotes granulosa cell proliferation. J. Cell Sci 2006b;119:3811-3821.
36. Gilchrist RB, Lane M, Thompson JG.Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality. Hum Reprod Update 2008; 14:159-177.
37. Glister C, Satchell L, Knight PG. Changes in expression of bone morphogenetic proteins (BMPs), their receptors and inhibin co-receptor betaglycan during bovine antral follicle development: inhibin can antagonize the suppressive effect of BMPs on theca androgen production. Reproduction 2010;140:699-712.
38. Gong X,McGee EA. Smad3 is required for normal follicular follicle-stimulating hormone responsiveness in the mouse. Biol Reprod 2009;81:730-738.
39. Gouédard L, Chen YG, Thevenet L, Racine C, Borie S, Lamarre I, Josso N, Massague J, di Clemente N. Engagement of bone morphogenetic protein type IB receptor and Smad1 signaling by anti-Müllerian hormone and its type II receptor. J Biol Chem 2000;275:27973-27978.
40. Gray PC, Bilezikjian LM, ValeW. Antagonism of activin by inhibin and inhibin receptors: a functional role for betaglycan. Mol Cell Endocrinol 2002; 188:254-260.
41. Hanrahan JP, Gregan SM, Mulsant P, Mullen M, Davis GH, Powell R, Galloway SM. Mutations in the genes for oocyte-derived growth factors GDF-9 and BMP-15 are associated with both increased ovulation rate and sterility in Cambridge and Belclare sheep (Ovis aries). Biol Reprod 2004;70:900-909.
42. Hata A, Lagna G, Massagué J, Hemmati-Brivanlou A. Smad6 inhibits BMP/ Smad1 signaling by specifically competing with the Smad4 tumor suppressor. Genes Dev 1998;12:186-197.
43. Hillier SG. Regulatory functions for inhibin and activin in human ovaries. J Endocrinol 1991;131:171-175.
44. Hillier SG. Paracrine support of ovarian stimulation. Mol Hum Reprod 2009; 15:843-850.
45. Hreinsson JG, Scott JE, Rasmussen C, Swahn ML, Hsueh AJ, Hovatta O. Growth differentiation factor-9 promotes the growth, development, and survival of human ovarian follicles in organ culture. J Clin Endocrinol Metab 2002;87:316-321.
46. Hsu DR, Economides AN,Wang X, Eimon PM, Harland RM. The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP activities. Mol Cell 1998;1:673-683.
47. Jaatinen R, Laitinen MP, Vuojolainen K, Aaltonen J, Louhio H, Heikinheimo K, Lehtonen E, Ritvos O. Localization of growth differentiation factor-9 (GDF-9) mRNA and protein in rat ovaries and cDNA cloning of rat GDF-9 and its novel homolog GDF-9B.Mol Cell Endocrinol 1999;156:189-193.
48. Jaatinen R, Bondestam J, Raivio T, Hilden K, Dunkel L, Groome N, Ritvos O. Activation of the bone morphogenetic protein signaling pathway induces inhibin b(B)-subunit mRNA and secreted inhibin B levels in cultured human granulosa-luteal cells. J Clin Endocrinol Metab 2002;87:1254-1261.
49. Jamin SP, Arango NA, Mishina Y, Hanks MC, Behringer RR. Requirement of Bmpr1a for Mullerian duct regression during male sexual development. Nat Genet 2002;32:408-410.
50. Juengel JL, McNatty KP. The role of proteins of the transforming growth factor-beta superfamily in the intraovarian regulation of follicular development. Hum Reprod Update 2005;11:143-160.
51. Juengel JL, Bodensteiner KJ, Heath DA, Hudson NL, Moeller CL, Smith P, Galloway SM, Davis GH, Sawyer HR, McNatty KP. Physiology of GDF9 and BMP15 signalling molecules. Anim Reprod Sci 2004a;82:447-460.
52. Juengel JL, Bibby AH, Reader KL, Lun S, Quirke LD, Haydon LJ, McNatty KP. The role of transforming growth factor-b (TGF-b) during ovarian follicular development in sheep. Reprod Biol Endocrinol 2004b;2:78-88.
53. Kaivo-Oja N, Bondestam J, Kämäräinen M, Koskimies J, Vitt U, Cranfield M, Vuojolainen K, Kallio JP, Olkkonen VM, Hayashi M et al. Growth differentiation factor-9 induces Smad2 activation and inhibin B production in cultured human granulosa-luteal cells. J Clin Endocrinol Metab 2003; 88:755-762.
54. Kaivo-Oja N, Mottershead DG, Mazerbourg S, Myllymaa S, Duprat S, Gilchrist RB, Groome NP, Hsueh AJ, Ritvos O. Adenoviral gene transfer allows Smad-responsive gene promoter analyses and delineation of type I receptor usage of transforming growth factor-beta family ligands in cultured human granulosa luteal cells. J Clin Endocrinol Metab 2005;90:271-278.
55. Kaivo-oja N, Jeffery LA, Ritvos O, Mottershead DG. Smad signalling in the ovary. Reprod Biol Endocrinol 2006;4:21.
56. Knight PG, Glister C. TGF-beta superfamily members and ovarian follicle development. Reproduction 2006;132:191-206.
57. KristensenSG, Rasmussen A, ByskovAG,AndersenCY. Isolation of pre-antral follicles fromhuman ovarianmedulla tissue.HumReprod 2011;26:157-166.
58. Kuo FT, Fan K, Ambartsumyan G, Menon P, Ketefian A, Bentsi-Barnes IK, Pisarska MD. Relative expression of genes encoding SMAD signal transduction factors in human granulosa cells is correlated with oocyte quality. J Assist Reprod Genet 2011;28:931-938.
59. Laitinen M, Vuojolainen K, Jaatinen R, Ketola I, Aaltonen J, Lehtonen E, Heikinheimo M, Ritvos O. A novel growth differentiation factor-9 (GDF-9) related factor is co-expressed with GDF-9 in mouse oocytes during folliculogenesis. Mech Dev 1998;78:135-140.
60. Lee WS, Otsuka F, Moore RK, Shimasaki S. Effect of bone morphogenetic protein-7 on folliculogenesis and ovulation in the rat. Biol. Reprod 2001; 65:994-999.
61. Lewis KA, Gray PC, Blount AL, MacConell LA, Wiater E, Bilezikjian LM, ValeW. Betaglycan binds inhibin and can mediate functional antagonism of activin signalling. Nature 2000;404:411-414.
62. Li Q, Rajanahally S, Edson MA, Matzuk MM. Stable expression and characterization of N-terminal tagged recombinant human bone morphogenetic protein 15. Mol Hum Reprod 2009;15:779-788.
63. LiaoWX,MooreRK,Otsuka F, Shimasaki S. Effect of intracellular interactionson the processing and secretion of bone morphogenetic protein-15 (BMP-15) and growth and differentiation factor-9: implication of the aberrant ovarian phenotype of BMP-15 mutant sheep. J Biol Chem2003;278:3713-3719.
64. Massagué J. TGF-bsignal transduction. Annu Rev Biochem 1998;67:753-791.
65. Matzuk MM, Burns KH, Viveiros MM, Eppig JJ. Intercellular communication in the mammalian ovary: oocytes carry the conversation. Science 2002; 296:2178-2180.
66. Mazerbourg S, Klein C, Roh J, Kaivo-Oja N, Mottershead DG, Korchynskyi O, Ritvos O, Hsueh AJ. Growth differentiation factor-9 signaling is mediated by the type I receptor, activin receptor-like kinase 5. Mol Endocrinol 2004;18:653-665.
67. McGee EA, Hsueh AJ. Initial and cyclic recruitment of ovarian follicles. Endocr Rev 2000;21:200-214.
68. McGee EA, Smith R, Spears N, Nachtigal MW, Ingraham H, Hsueh AJ. Müllerian inhibitory substance induces growth of rat preantral ovarian follicles. Biol Reprod 2001;64:293-298.
69. McIntosh CJ, Lun S, Lawrence S,Western AH, McNatty KP, Juengel JL. The proregion of mouse BMP15 regulates the cooperative interactions of BMP15 and GDF9. Biol Reprod 2008;79:889-896.
70. McNatty KP, Heath DA, Lundy T, Fidler AE, Quirke L, O'Connell A, Smith P, Groome N, Tisdall DJ. Control of early ovarian follicular development. J Reprod Fertil Suppl 1999;54:3-16.
71. McNatty KP, Juengel JL, Reader KL, Lun S, Myllymaa S, Lawrence SB, Western A, Meerasahib MF, Mottershead DG, Groome NP et al. Bone morphogenetic protein 15 and growth differentiation factor 9 co-operate to regulate granulosa cell function in ruminants. Reproduction 2005a;129:481-487.
72. McNatty KP, Smith P, Moore LG, Reader K, Lun S, Hanrahan JP, GroomeNP, Laitinen M, Ritvos O, Juengel JL. Oocyte-expressed genes affecting ovulation rate. Mol Cell Endocrinol 2005b;29:57-66.
73. Mishina Y, Rey R, Finegold MJ, Matzuk MM, Josso N, Cate RL, Behringer RR. Genetic analysis of the Müllerian-inhibiting substance signal transduction pathway inmammalian sexual differentiation. GenesDev 1996;15:2577-2587.
74. Moore RK, Otsuka F, Shimasaki S. Molecular basis of bone morphogenetic protein-15 signaling in granulosa cells. J Biol Chem 2003;278:304-310.
75. Mottershead DG, Ritter LJ, Gilchrist RB. Signalling pathways mediating specific synergistic interactions between GDF9 and BMP15. Mol Hum Reprod 2012;18:121-128.
76. Myers M, Pangas SA. Regulatory roles of transforming growth factor beta family members in folliculogenesis. Wiley Interdiscip Rev Syst Biol Med 2010;2:117-125.
77. Nakamura T, Takio K, Eto Y, Shibai H, Titani K, Sugino H. Activin-binding protein from rat ovary is follistatin. Science 1990;247:836-838.
78. Nakao A, Afrakhte M, Moren A, Nakayama T, Christian JL, Heuchel R, Itoh S, Kawabata M, Heldin NE, Heldin CH et al. Identification of Smad7, a TGF beta-inducible antagonist of TGF-b signalling. Nature 1997;389:631-635.
79. Nilsson EE, Skinner MK. Bone morphogenetic protein-4 acts as an ovarian follicle survival factor and promotes primordial follicle development. Biol Reprod 2003;69:1265-1272.
80. Oka C, Tsujimoto R, Kajikawa M, Koshiba-Takeuchi K, Ina J, Yano M, Tsuchiya A, Ueta Y, Soma A, Kanda H et al. HtrA1 serine protease inhibits signaling mediated by Tgf-b family proteins. Development 2004; 131:1041-1053.
81. Onichtchouk D, Chen YG, Dosch R, Gawantka V, Delius H, Massague J, Niehrs C. Silencing of TGF-beta signalling by the pseudoreceptor BAMBI. Nature 1999;401:480-485.
82. Oron G, Fisch B, Ao A, Zhang XY, Farhi J, Ben-Haroush A, Kesseler-Icekson G, Abir R. Expression of growth-differentiating factor 9 and its type 1 receptor in human ovaries. Reprod Biomed Online 2010; 21:109-117.
83. Otsuka F, Yao Z, Lee T, Yamamoto S, Erickson GF, Shimasaki S. Bone morphogenetic protein-15. Identification of target cells and biological functions. J Biol Chem 2000;275:39523-39528.
84. Otsuka F, Moore RK, Shimasaki S. Biological function and cellular mechanism of bone morphogenetic protein-6 in the ovary. J Biol Chem 2001; 276:32889-32895.
85. Otsuka F, McTavish KJ, Shimasaki S. Integral role of GDF-9 and BMP-15 in ovarian function. Mol Reprod Dev 2011a;78:9-21.
86. Otsuka F, McTavish KJ, Shimasaki S. Integral role of GDF-9 and BMP-15 in ovarian function. Mol Reprod Dev 2011b;78:9-21.
87. Pangas SA. Bone morphogenetic protein signaling transcription factor (SMAD) function in granulosa cells. Mol Cell Endocrinol 2012a;5:40-47.
88. Pangas SA. Regulation of the ovarian reserve by members of the transforming growth factor beta family. Mol Reprod Dev 2012b;79:666-679.
89. Pangas SA, Matzuk MM. The art and artifact of GDF9 activity: cumulus expansion and the cumulus expansion-enabling factor. Biol Reprod 2005; 73:582-585.
90. Pangas SA, Matzuk MM. The TGF-b family in the reproductive tract. In: Derynck R, Miyazono K (eds). The TGF-b Family. New York: Cold Spring Harbor Laboratory Press, 2008, 861-889.
91. Pangas SA, Rademaker AW, Fishman DA,Woodruff TK. Localization of the activin signal transduction components in normal human ovarian follicles: implications for autocrine and paracrine signaling in the ovary. J Clin Endocrinol Metab 2002;87:2644-2657.
92. Paradis F,Novak S, MurdochGK, DyckMK,DixonWT, FoxcroftGR. Temporal regulation of BMP2, BMP6, BMP15, GDF9, BMPR1A, BMPR1B, BMPR2 and TGFBR1 mRNA expression in the oocyte, granulosa and theca cells of developing preovulatory follicles in the pig. Reproduction 2009;138:115-129.
93. Pierreux CE, Nicolas FJ, Hill CS. Transforming growth factor beta-independent shuttling of Smad4 between the cytoplasm and nucleus. Mol Cell Biol 2000; 20:9041-9054.
94. Qu J, Godin PA, Nisolle M, Donnez J. Expression of receptors for insulin-like growth factor-I and transforming growth factor-b in human follicles. Mol Hum Reprod 2000;6:137-145.
95. Rabinovici J, Goldsmith PC, Roberts VJ, Vaughan J, ValeW, Jaffe RB. Localization and secretion of inhibin/activin subunits in the human and subhuman primate fetal gonads. J Clin Endocrinol Metab 1991;73:1141-1149.
96. Rajpert-DeMeyts E, Jorgensen N, Graem N, Muller J, Cate RL, Skakkebaek NE. Expression of anti-Mullerian hormone during normal and pathological gonadal development: association with differentiation of Sertoli and granulosa cells. J Clin Endocrinol Metab 1999;84:3836-3844.
97. Roy SK, Kole AR. Ovarian transforming growth factor-b (TGF-b) receptors: in-vitro effects of follicle stimulating hormone, epidermal growth factorand TGF-b on receptor expression in human preantral follicles. Mol Hum Reprod 1998;4:207-214.
98. Sadeu JC, Adriaenssens T, Smitz J. Expression of growth differentiation factor 9, bone morphogenetic protein 15, and anti-Mullerian hormone in cultured mouse primary follicles. Reproduction 2008;136:195-203.
99. Schmidt KL, Kryger-Baggesen N, Byskov AG, Andersen CY. Anti-müllerian hormone initiates growth of human primordial follicles in vitro. Mol Cell Endocrinol 2005;234:87-93.
100. Schneider L, Clement CA, Teilmann SC, Pazour GJ, Hoffmann EK, Satir P, Christensen ST. PDGFRalphaalpha signalling is regulated through the primary cilium in fibroblasts. Curr Biol 2005;15:1861-1866.
101. Schwall RH, Mason AJ, Wilcox JN, Bassett SG, Zeleznik AJ. Localization of inhibin/activin subunit mRNAs within the primate ovary. Mol Endocrinol 1990;4:75-79.
102. Shi Y, Massagué J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 2003;113:685-700.
103. Shimasaki S, Zachow RJ, Li D, Kim H, Iemura S-I, Ueno N, Sampath K, Chang RJ, Erickson GF. A functional bone morphogenetic protein system in the ovary. Proc Natl Acad Sci USA 1999;96:7282-7287.
104. Shimasaki S,Moore RK, EricksonGF, Otsuka F. The role of bonemorphogenetic proteins in ovarian function. Reprod Suppl 2003;61:323-337.
105. Souza CJ, Campbell BK, McNeilly AS, Baird DT. Effect of bone morphogenetic protein 2 (BMP2) on oestradiol and inhibin A production by sheep granulosa cells, and localization of BMP receptors in the ovary by immunohistochemistry. Reproduction 2002; 123:363-369.
106. Stenvers KL, Findlay JK. Inhibins: from reproductive hormones to tumor suppressors. Trends Endocrinol Metab 2010;21:174-180.
107. Stubbs SA, Hardy K, Da Silva-Buttkus P, Stark J, Webber LJ, Flanagan AM, Themmen AP, Visser JA, Groome NP, Franks S. Anti-Mullerian hormone protein expression is reduced during the initial stages of follicle development in human polycystic ovaries. J Clin Endocrinol Metab 2005; 90:5536-5543.
108. Sugiura K, Su YQ, Eppig JJ. Does bone morphogenetic protein 6 (BMP6) affect female fertility in the mouse? Biol Reprod 2010;83:997-1004.
109. Thompson TB,Woodruff TK, Jardetzky TS. Structures of an ActRIIB:activin A complex reveal a novel binding mode for TGF-beta ligand:receptor interactions. EMBO J 2003;22:1555-1566.
110. Ueno S, Kuroda T, Maclaughlin DT, Ragin RC, Manganaro TF, Donahoe PK. Müllerian inhibiting substance in the adult rat ovary duringvarious stages of the estrous cycle. Endocrinology 1989a;125:1060-1066.
111. Ueno S, Takahashi M, Manganaro TF, Ragin RC, Donahoe PK. Cellular localization of müllerian inhibiting substance in the developing rat ovary. Endocrinology 1989b;124:1000-1006.
112. Vigier B, Picard JY, Tran D, Legeai L, Josso N. Production of anti-Müllerian hormone: another homology between Sertoli and granulose cells. Endocrinology 1984;114:1315-1320.
113. Visser JA, Themmen AP. Anti-Mullerian hormone and folliculogenesis. Mol Cell Endocrinol. 2005;29:81-86.
114. Visser JA, Olaso R, Verhoef-Post M, Kramer P, Themmen AP, Ingraham HA. The serine/threonine transmembrane receptor ALK2 mediates Müllerian inhibiting substance signaling. Mol Endocrinol 2001;15:936-945.
115. Visser JA, de Jong FH, Laven JS, Themmen AP. Anti-Mullerian hormone: a new marker for ovarian function. Reproduction 2006;131:1-9.
116. Vitt UA, Mazerbourg S, Klein C, Hsueh AJ. Bone morphogenetic protein receptor type II is a receptor for growth differentiation factor-9. Biol Reprod 2002;67:473-480.
117. Wang J,Roy SK. Growth differentiation factor-9 and stem cell factor promote primordial follicle formation in the hamster: modulation by folliclestimulating hormone. Biol Reprod 2004;70:577-585.
118. Weenen C, Laven JS, Von Bergh AR, Cranfield M, Groome NP, Visser JA, Kramer P, Fauser BC, Themmen AP. Anti-Müllerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod 2004;10:77-83.
119. Wilson T, Wu XY, Juengel JL, Ross IK, Lumsden JM, Lord EA, Dodds KG, Walling GA, McEwan JC, O'Connell AR et al. Highly prolific Booroola sheep have a mutation in the intracellular kinase domain of bone morphogenetic protein IB receptor (ALK-6) that is expressed in both oocytes and granulosa cells. Biol Reprod 2001;64:1225-1235.
120. Xu J, Oakley J, McGee EA. Stage-specific expression of Smad2 and Smad3 during folliculogenesis. Biol Reprod 2002;66:1571-1578.
121. Yamoto M, Minami S, Nakano R, Kobayashi M. Immunohistochemical localization of inhibin/activin subunits in human ovarian follicles during the menstrual cycle. J Clin Endocrinol Metab 1992;74:989-993.
122. Yan C, Wang P, DeMayo J, DeMayo FJ, Elvin JA, Carino C, Prasad SV, Skinner SS, Dunbar BS, Dube JL et al. Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Mol Endocrinol 2001;1:854-866.
123. Ying SY. Inhibins and activins: chemical properties and biological activity. Proc Soc Exp Biol Med 1987;186:253-264.
124. Zhang Y, Chang C, Gehling DJ,Hemmati-Brivanlou A, Derynck R. Regulation of Smad degradation and activity by Smurf2, an E3 ubiquitin ligase. Proc Natl Acad Sci USA 2001;98:974-979.
125. Zhu H, Kavsak P, Abdollah S, Wrana JL, Thomsen GH. A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation. Nature 1999;400:687-693.
126. Zhu J, Lin SJ, Zou C, Makanji Y, Jardetzky TS, Woodruff TK. Inhibin alpha-Subunit N Terminus Interacts with Activin Type IB Receptor to Disrupt Activin Signaling. J Biol Chem 2012;287:8060-8070.