Oocyte-somatic cell interactions in the human ovary-novel role of bone morphogenetic proteins and growth differentiation factors

Human Reproduction Update

Volumn 23, Issue 1, 2016, Pages 1-18

  Chang, Hsun Ming ^a,b   Qiao, Jie ^a   Leung, Peter C K ^b  

^a PEKING UNIVERSITY THIRD HOSPITAL   (China)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

Activin receptor like kinase; Bone morphogenetic proteins; Female infertility; Growth differentiation factors; Human granulosa cell line; Human granulosa cells; Human ovary

Indexed keywords

BONE MORPHOGENETIC PROTEIN; BONE MORPHOGENETIC PROTEIN RECEPTOR; GROWTH DIFFERENTIATION FACTOR; GROWTH FACTOR RECEPTOR; MYOSTATIN; RECOMBINANT BONE MORPHOGENETIC PROTEIN; REGULATOR PROTEIN; TRANSFORMING GROWTH FACTOR BETA;

ARTICLE; CELL COMMUNICATION; CELL EXPANSION; CELL FUNCTION; CELL IMMORTALIZATION; CELL INTERACTION; CELL PROLIFERATION; CUMULUS CELL; ENDOMETRIOSIS; EXTRACELLULAR MATRIX; FEMALE INFERTILITY; GRANULOSA CELL; GYNECOLOGIC DISEASE; HUMAN; INTRACELLULAR SIGNALING; LUTEAL CELL; LUTEINIZATION; NONHUMAN; OOCYTE; OOCYTE MATURATION; OVARY DISEASE; OVARY FOLLICLE DEVELOPMENT; OVARY FUNCTION; OVARY POLYCYSTIC DISEASE; OVULATION; PHENOTYPE; PREMATURE OVARIAN FAILURE; PRIMORDIAL GERM CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; SOMATIC CELL; STEROIDOGENESIS; STROMA CELL; THECA CELL; ANIMAL; FEMALE; METABOLISM; MOUSE; OOCYTE DEVELOPMENT; OVARY; OVARY FOLLICLE; PHYSIOLOGY;

ANIMALS; BONE MORPHOGENETIC PROTEINS; CELL COMMUNICATION; FEMALE; GROWTH DIFFERENTIATION FACTORS; HUMANS; MICE; OOCYTES; OOGENESIS; OVARIAN FOLLICLE; OVARY; OVULATION; TRANSFORMING GROWTH FACTOR BETA;

EID: 85020050553     PISSN: 13554786     EISSN: 14602369     Source Type: Journal    
DOI: 10.1093/humupd/dmw039     Document Type: Article

References (213)

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. Achache H, Revel A. Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update 2006;12:731-746
4. Ackert CL, Gittens JE, O'Brien MJ, Eppig JJ, Kidder GM. Intercellular communication via connexin43 gap junctions is required for ovarian folliculogenesis in the mouse. Dev Biol 2001;233:258-270
5. Al-Azemi M, Kyrou D, Kolibianakis EM, Humaidan P, Van Vaerenbergh I, Devroey P, Fatemi HM. Elevated progesterone during ovarian stimulation for IVF. Reprod Biomed Online 2012;24:381-388
6. Albertini DF, Combelles CM, Benecchi E, Carabatsos MJ. Cellular basis for paracrine regulation of ovarian follicle development. Reproduction 2001;121: 647-653
7. Armstrong DT, Xia P, de Gannes G, Tekpetey FR, Khamsi F. Differential effects of insulin-like growth factor-I and follicle-stimulating hormone on proliferation and differentiation of bovine cumulus cells and granulosa cells. Biol Reprod 1996;54: 331-338
8. Athanasios F, Afrodite N, Effstratios P, Demetrios K. Co-expression of bone morphogenetic protein 6 with estrogen receptor a in endometriosis. Arch Gynecol Obstet 2012;285:1001-1007
9. Auclair S, Rossetti R, Meslin C, Monestier O, Di Pasquale E, Pascal G, Persani L, Fabre S. Positive selection in bone morphogenetic protein 15 targets a natural mutation associated with primary ovarian insufficiency in human. PLoS One 2013; 8:e78199
10. Baerwald AR, Adams GP, Pierson RA. Ovarian antral folliculogenesis during the human menstrual cycle: a review. Hum Reprod Update 2012;18:73-91
11. Ball GD, Leibfried ML, Lenz RW, Ax RL, Bavister BD, First NL. Factors affecting successful in vitro fertilization of bovine follicular oocytes. Biol Reprod 1983;28: 717-725
12. Baranova NS, Inforzato A, Briggs DC, Tilakaratna V, Enghild JJ, Thakar D, Milner CM, Day AJ, Richter RP. Incorporation of pentraxin 3 into hyaluronan matrices is tightly regulated and promotes matrix cross-linking. J Biol Chem 2014;289: 30481-30498
13. Bayasula, Iwase A, Kiyono T, Takikawa S, Goto M, Nakamura T, Nagatomo Y, Nakahara T, Kotani T, Kobayashi H et al. Establishment of a human nonluteinized granulosa cell line that transitions from the gonadotropin-independent to the gonadotropin-dependent status. Endocrinology 2012;153:2851-2860
14. Bayne RA, Kinnell HL, Coutts SM, He J, Childs AJ, Anderson RA. GDF9 is transiently expressed in oocytes before follicle formation in the human fetal ovary and is regulated by a novel NOBOX transcript. PLoS One 2015;10:e0119819
15. Bier E, De Robertis EM. EMBRYO DEVELOPMENT. BMP gradients: a paradigm for morphogen-mediated developmental patterning. Science 2015;348:aaa5838
16. 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
17. Breckwoldt M, Selvaraj N, Aharoni D, Barash A, Segal I, Insler V, Amsterdam A. Expression of Ad4-BP/cytochrome P450 side chain cleavage enzyme and induction of cell death in long-term cultures of human granulosa cells. Mol Hum Reprod 1996;2:391-400
18. Buccione R, Vanderhyden BC, Caron PJ, Eppig JJ. FSH-induced expansion of the mouse cumulus oophorus in vitro is dependent upon a specific factor(s) secreted by the oocyte. Dev Biol 1990;138:16-25
19. Bulun SE, Monsivais D, Kakinuma T, Furukawa Y, Bernardi L, Pavone ME, Dyson M. Molecular biology of endometriosis: from aromatase to genomic abnormalities. Semin Reprod Med 2015;33:220-224
20. Caspar DL, Goodenough DA, Makowski L, Phillips WC. Gap junction structures. I. Correlated electron microscopy and x-ray diffraction. J Cell Biol 1977;74:605-628
21. Chand AL, Ponnampalam AP, Harris SE, Winship IM, Shelling AN. Mutational analysis of BMP15 and GDF9 as candidate genes for premature ovarian failure. Fertil Steril 2006;86:1009-1012
22. Chang HM, Cheng JC, Fang L, Qiu X, Klausen C, Taylor EL, Leung PC. Recombinant BMP4 and BMP7 downregulate pentraxin 3 in human granulosa cells. J Clin Endocrinol Metab 2015a;100:E365-374
23. Chang HM, Cheng JC, Huang HF, Shi FT, Leung PC. Activin A, B and AB decrease progesterone production by down-regulating StAR in human granulosa cells. Mol Cell Endocrinol 2015b;412:290-301
24. Chang HM, Cheng JC, Klausen C, Leung PC. BMP15 suppresses progesterone production by down-regulating StAR via ALK3 in human granulosa cells. Mol Endocrinol 2013a;27:2093-2104
25. Chang HM, Cheng JC, Klausen C, Leung PC. Recombinant BMP4 and BMP7 increase activin A production by up-regulating inhibin betaA subunit and furin expression in human granulosa-lutein cells. J Clin Endocrinol Metab 2015c;100: E375-386
26. Chang HM, Cheng JC, Klausen C, Taylor EL, Leung PC. Effects of recombinant activins on steroidogenesis in human granulosa-lutein cells. J Clin Endocrinol Metab 2014;99:E1922-1932
27. Chang HM, Cheng JC, Leung PC. Theca-derived BMP4 and BMP7 down-regulate connexin43 expression and decrease gap junction intercellular communication activity in immortalized human granulosa cells. J Clin Endocrinol Metab 2013b;98: E437-445
28. Chang HM, Cheng JC, Liu Y, Klausen C, Xu C, Leung PC. Activin A-induced increase in LOX activity in human granulosa-lutein cells is mediated by CTGF. Reproduction 2016a;152:293-301
29. Chang HM, Cheng JC, Taylor E, Leung PC. Oocyte-derived BMP15 but not GDF9 down-regulates connexin43 expression and decreases gap junction intercellular communication activity in immortalized human granulosa cells. Mol Hum Reprod 2014;20:373-383
30. Chang HM, Fang L, Cheng JC, Klausen C, Sun YP, Leung PC. Growth differentiation factor 8 down-regulates pentraxin 3 in human granulosa cells. Mol Cell Endocrinol 2015d;404:82-90
31. Chang HM, Fang L, Cheng JC, Taylor EL, Sun YP, Leung PC. Effects of growth differentiation factor 8 on steroidogenesis in human granulosa-lutein cells. Fertil Steril 2016b;105:520-528
32. Chang HM, Fang Y, Liu PP, Cheng JC, Yang X, Leung PC. Connective tissue growth factor mediates growth differentiation factor 8-induced increase of lysyl oxidase activity in human granulosa-lutein cells. Mol Cell Endocrinol 2016c;434:186-198
33. Chang HM, Pan HH, Cheng JC, Zhu YM, Leung PC. Growth differentiation factor 8 suppresses cell proliferation by up-regulating CTGF expression in human granulosa cells. Mol Cell Endocrinol 2016c;422:9-17
34. Chen MJ, Han DS, Yang JH, Yang YS, Ho HN, Yang WS. Myostatin and its association with abdominal obesity, androgen and follistatin levels in women with polycystic ovary syndrome. Hum Reprod 2012;27:2476-2483
35. Chen YC, Chang HM, Cheng JC, Tsai HD, Wu CH, Leung PC. Transforming growth factor-beta1 up-regulates connexin43 expression in human granulosa cells. Hum Reprod 2015;30:2190-2201
36. Childs AJ, Kinnell HL, Collins CS, Hogg K, Bayne RA, Green SJ, McNeilly AS, Anderson RA. BMP signaling in the human fetal ovary is developmentally regulated and promotes primordial germ cell apoptosis. Stem Cells 2010;28:1368-1378
37. Clementi C, Tripurani SK, Large MJ, Edson MA, Creighton CJ, Hawkins SM, Kovanci E, Kaartinen V, Lydon JP, Pangas SA et al. Activin-like kinase 2 functions in peri-implantation uterine signaling in mice and humans. PLoS Genet 2013;9: e1003863
38. Clop A, Marcq F, Takeda H, Pirottin D, Tordoir X, Bibe B, Bouix J, Caiment F, Elsen JM, Eychenne F et al. A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep. Nat Genet 2006;38:813-818
39. Coskun S, Uzumcu M, Lin YC, Friedman CI, Alak BM. Regulation of cumulus cell steroidogenesis by the porcine oocyte and preliminary characterization of oocyte-produced factor(s). Biol Reprod 1995;53:670-675
40. Crispi S, Piccolo MT, D'Avino A, Donizetti A, Viceconte R, Spyrou M, Calogero RA, Baldi A, Signorile PG. Transcriptional profiling of endometriosis tissues identifies genes related to organogenesis defects. J Cell Physiol 2013;228: 1927-1934
41. Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGFbeta family signalling. Nature 2003;425:577-584
42. Di Pasquale E, Beck-Peccoz P, Persani L. Hypergonadotropic ovarian failure associated with an inherited mutation of human bone morphogenetic protein-15 (BMP15) gene. Am J Hum Genet 2004;75:106-111
43. Di Pasquale E, Rossetti R, Marozzi A, Bodega B, Borgato S, Cavallo L, Einaudi S, Radetti G, Russo G, Sacco M et al. Identification of new variants of human BMP15 gene in a large cohort of women with premature ovarian failure. J Clin Endocrinol Metab 2006;91:1976-1979
44. Diaz FJ, Wigglesworth K, Eppig JJ. Oocytes determine cumulus cell lineage in mouse ovarian follicles. J Cell Sci 2007;120:1330-1340
45. Dixit H, Rao LK, Padmalatha V, Kanakavalli M, Deenadayal M, Gupta N, Chakravarty B, Singh L. Mutational screening of the coding region of growth differentiation factor 9 gene in Indian women with ovarian failure. Menopause 2005; 12:749-754
46. Dixit H, Rao LK, Padmalatha VV, Kanakavalli M, Deenadayal M, Gupta N, Chakrabarty B, Singh L. Missense mutations in the BMP15 gene are associated with ovarian failure. Hum Genet 2006;119:408-415
47. Drummond AE. TGFbeta signalling in the development of ovarian function. Cell Tissue Res 2005;322:107-115
48. Ducy P, Karsenty G. The family of bone morphogenetic proteins. Kidney Int 2000; 57:2207-2214
49. el-Fouly MA, Cook B, Nekola M, Nalbandov AV. Role of the ovum in follicular luteinization. Endocrinology 1970;87:286-293
50. Elvin JA, Clark AT, Wang P, Wolfman NM, Matzuk MM. Paracrine actions of growth differentiation factor-9 in the mammalian ovary. Mol Endocrinol 1999;13: 1035-1048
51. Eppig JJ. Regulation of cumulus oophorus expansion by gonadotropins in vivo and in vitro. Biol Reprod 1980;23:545-552
52. Eppig JJ. Oocyte control of ovarian follicular development and function in mammals. Reproduction 2001;122:829-838
53. Eppig JJ, Wigglesworth K, Pendola F, Hirao Y. Murine oocytes suppress expression of luteinizing hormone receptor messenger ribonucleic acid by granulosa cells. Biol Reprod 1997;56:976-984
54. Erickson GF, 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;1:9
55. Fang L, Chang HM, Cheng JC, Yu Y, Leung PC, Sun YP. Growth differentiation factor-8 decreases StAR expression through ALK5-mediated Smad3 and ERK1/2 signaling pathways in luteinized human granulosa cells. Endocrinology 2015;156: 4684-4694
56. Fang L, Cheng JC, Chang HM, Sun YP, Leung PC. EGF-like growth factors induce COX-2-derived PGE2 production through ERK1/2 in human granulosa cells. J Clin Endocrinol Metab 2013;98:4932-4941
57. Fang L, Yu Y, Zhang R, He J, Sun YP. Serum GDF-8 levels change dynamically during controlled ovarian hyperstimulation in patients undergoing IVF/ICSI-ET. Sci Rep 2016b;6:28036
58. Fang Y, Chang HM, Cheng JC, Klausen C, Leung PC, Yang X. Transforming growth factor-beta1 increases lysyl oxidase expression by downregulating MIR29A in human granulosa lutein cells. Reproduction 2016a;152:205-213
59. Ferrarini E, Russo L, Fruzzetti F, Agretti P, De Marco G, Dimida A, Gianetti E, Simoncini T, Simi P, Baldinotti F et al. Clinical characteristics and genetic analysis in women with premature ovarian insufficiency. Maturitas 2013;74:61-67
60. Foote RH. In vitro fertilization and embryo transfer in domestic animals: applications in animals and implications for humans. J In Vitro Fert Embryo Transf 1987;4:73-88
61. Fraidenraich D, Lang R, Basilico C. Distinct regulatory elements govern Fgf4 gene expression in the mouse blastocyst, myotomes, and developing limb. Dev Biol 1998;204:197-209
62. Franks S, Stark J, Hardy K. Follicle dynamics and anovulation in polycystic ovary syndrome. Hum Reprod Update 2008;14:367-378
63. Furger C, Cronier L, Poirot C, Pouchelet M. Human granulosa cells in culture exhibit functional cyclic AMP-regulated gap junctions. Mol Hum Reprod 1996;2: 541-548
64. Gamer LW, Wolfman NM, Celeste AJ, Hattersley G, Hewick R, Rosen V. A novel BMP expressed in developing mouse limb, spinal cord, and tail bud is a potent mesoderm inducer in Xenopus embryos. Dev Biol 1999;208:222-232
65. Gautschi OP, Frey SP, Zellweger R. Bone morphogenetic proteins in clinical applications. ANZ J Surg 2007;77:626-631
66. Gershon E, Plaks V, Dekel N. Gap junctions in the ovary: expression, localization and function. Mol Cell Endocrinol 2008;282:18-25
67. Gilchrist RB, Lane M, Thompson JG. Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality. Hum Reprod Update 2008;14:159-177
68. Gilchrist RB, Ritter LJ, Armstrong DT. Mouse oocyte mitogenic activity is developmentally coordinated throughout folliculogenesis and meiotic maturation. Dev Biol 2001;240:289-298
69. Gilchrist RB, Ritter LJ, Armstrong DT. Oocyte-somatic cell interactions during follicle development in mammals. Anim Reprod Sci 2004;82-83:431-446
70. Gittens JE, Barr KJ, Vanderhyden BC, Kidder GM. Interplay between paracrine signaling and gap junctional communication in ovarian follicles. J Cell Sci 2005;118: 113-122
71. Gonzalez A, Ramirez-Lorca R, Calatayud C, Mendoza N, Ruiz A, Saez ME, Moron FJ. Association of genetic markers within the BMP15 gene with anovulation and infertility in women with polycystic ovary syndrome. Fertil Steril 2008;90:447-449
72. Gougeon A. Regulation of ovarian follicular development in primates: facts and hypotheses. Endocr Rev 1996;17:121-155
73. Granot I, Dekel N. The ovarian gap junction protein connexin43: regulation by gonadotropins. Trends Endocrinol Metab 2002;13:310-313
74. Grondahl ML, Nielsen ME, Dal Canto MB, Fadini R, Rasmussen IA, Westergaard LG, Kristensen SG, Yding Andersen C. Anti-Mullerian hormone remains highly expressed in human cumulus cells during the final stages of folliculogenesis. Reprod Biomed Online 2011;22:389-398
75. Guo J, Tian T, Lu D, Xia G, Wang H, Dong M. Alterations of maternal serum and placental follistatin-like 3 and myostatin in pre-eclampsia. J Obstet Gynaecol Res 2012;38:988-996
76. Harrison CA, Al-Musawi SL, Walton KL. Prodomains regulate the synthesis, extracellular localisation and activity of TGF-beta superfamily ligands. Growth Factors 2011;29:174-186
77. Havelock JC, Rainey WE, Carr BR. Ovarian granulosa cell lines. Mol Cell Endocrinol 2004;228:67-78
78. Hawinkels LJ, Garcia de Vinuesa A, Ten Dijke P. Activin receptor-like kinase 1 as a target for anti-angiogenesis therapy. Expert Opin Investig Drugs 2013;22:1371-1383
79. Hayashi M, McGee EA, Min G, Klein C, Rose UM, van Duin M, Hsueh AJ. Recombinant growth differentiation factor-9 (GDF-9) enhances growth and differentiation of cultured early ovarian follicles. Endocrinology 1999;140:1236-1244
80. Hickey TE, Marrocco DL, Gilchrist RB, Norman RJ, Armstrong DT. Interactions between androgen and growth factors in granulosa cell subtypes of porcine antral follicles. Biol Reprod 2004;71:45-52
81. Hogan BL. Bone morphogenetic proteins: multifunctional regulators of vertebrate development. Genes Dev 1996;10:1580-1594
82. Holtzhausen A, Golzio C, How T, Lee YH, Schiemann WP, Katsanis N, Blobe GC. Novel bone morphogenetic protein signaling through Smad2 and Smad3 to regulate cancer progression and development. FASEB J 2014;28:1248-1267
83. Hosokawa K, Dantes A, Schere-Levy C, Barash A, Yoshida Y, Kotsuji F, Vlodavsky I, Amsterdam A. Induction of Ad4BP/SF-1, steroidogenic acute regulatory protein, and cytochrome P450scc enzyme system expression in newly established human granulosa cell lines. Endocrinology 1998;139:4679-4687
84. Hsieh M, Zamah AM, Conti M. Epidermal growth factor-like growth factors in the follicular fluid: role in oocyte development and maturation. Semin Reprod Med 2009;27:52-61
85. Huang HY, Wang HS, Chan SH, Lee CL, Wang CW, Soong YK. Granulosa-lutein cell growth differentiation factor-9 (GDF-9) messenger RNA and protein expression in in vitro fertilization (IVF) cycles: relation to characteristics of ovulation induction and IVF. Fertil Steril 2009;91:1583-1585
86. Huang X, Hao C, Shen X, Zhang Y, Liu X. RUNX2, GPX3 and PTX3 gene expression profiling in cumulus cells are reflective oocyte/embryo competence and potentially reliable predictors of embryo developmental competence in PCOS patients. Reprod Biol Endocrinol 2013;11:109
87. Huang Z, Wells D. The human oocyte and cumulus cells relationship: new insights from the cumulus cell transcriptome. Mol Hum Reprod 2010;16:715-725
88. Hussein MR. Apoptosis in the ovary: molecular mechanisms. Hum Reprod Update 2005;11:162-177
89. Ishiwata I, Ishiwata C, Soma M, Kobayashi N, Ishikawa H. Establishment and characterization of an estrogen-producing human ovarian granulosa tumor cell line. J Natl Cancer Inst 1984;72:789-800
90. Islam MS, Catherino WH, Protic O, Janjusevic M, Gray PC, Giannubilo SR, Ciavattini A, Lamanna P, Tranquilli AL, Petraglia F et al. Role of activin-A and myostatin and their signaling pathway in human myometrial and leiomyoma cell function. J Clin Endocrinol Metab 2014;99:E775-785
91. Israel DI, Nove J, Kerns KM, Kaufman RJ, Rosen V, Cox KA, Wozney JM. Heterodimeric bone morphogenetic proteins show enhanced activity in vitro and in vivo. Growth Factors 1996;13:291-300
92. Jiang JY, Xiong H, Cao M, Xia X, Sirard MA, Tsang BK. Mural granulosa cell gene expression associated with oocyte developmental competence. J Ovarian Res 2010;3:6
93. Juengel JL, McNatty KP. The role of proteins of the transforming growth factorbeta superfamily in the intraovarian regulation of follicular development. Hum Reprod Update 2005;11:143-160
94. Kagan HM, Trackman PC. Properties and function of lysyl oxidase. Am J Respir Cell Mol Biol 1991;5:206-210
95. Kaivo-Oja N, Bondestam J, Kamarainen 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
96. Kemaladewi DU, de Gorter DJ, Aartsma-Rus A, van Ommen GJ, ten Dijke P, tHoen PA, Hoogaars WM. Cell-type specific regulation of myostatin signaling. FASEB J 2012;26:1462-1472
97. Khalaf M, Morera J, Bourret A, Reznik Y, Denoual C, Herlicoviez M, Mittre H, Benhaim A. BMP system expression in GCs from polycystic ovary syndrome women and the in vitro effects of BMP4, BMP6, and BMP7 on GC steroidogenesis. Eur J Endocrinol 2013;168:437-444
98. Khan DR, Fournier E, Dufort I, Richard FJ, Singh J, Sirard MA. Meta-analysis of gene expression profiles in granulosa cells during folliculogenesis. Reproduction 2016; 151:R103-110
99. Kinouchi N, Ohsawa Y, Ishimaru N, Ohuchi H, Sunada Y, Hayashi Y, Tanimoto Y, Moriyama K, Noji S. Atelocollagen-mediated local and systemic applications of myostatin-targeting siRNA increase skeletal muscle mass. Gene Ther 2008;15: 1126-1130
100. Knight PG, Glister C. TGF-beta superfamily members and ovarian follicle development. Reproduction 2006;132:191-206
101. Kovanci E, Rohozinski J, Simpson JL, Heard MJ, Bishop CE, Carson SA. Growth differentiating factor-9 mutations may be associated with premature ovarian failure. Fertil Steril 2007;87:143-146
102. Kristensen SG, Andersen K, Clement CA, Franks S, Hardy K, Andersen CY. Expression of TGF-beta superfamily growth factors, their receptors, the associated SMADs and antagonists in five isolated size-matched populations of preantral follicles from normal human ovaries. Mol Hum Reprod 2014;20:293-308
103. Kubota K, Sato F, Aramaki S, Soh T, Yamauchi N, Hattori MA. Ubiquitous expression of myostatin in chicken embryonic tissues: its high expression in testis and ovary. Comp Biochem Physiol A Mol Integr Physiol 2007;148:550-555
104. Laissue P, Christin-Maitre S, Touraine P, Kuttenn F, Ritvos O, Aittomaki K, Bourcigaux N, Jacquesson L, Bouchard P, Frydman R et al. Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure. Eur J Endocrinol 2006;154:739-744
105. Lawson KA, Dunn NR, Roelen BA, Zeinstra LM, Davis AM, Wright CV, Korving JP, Hogan BL. Bmp4 is required for the generation of primordial germ cells in the mouse embryo. Genes Dev 1999;13:424-436
106. Lee J, Wikesjo UM. Growth/differentiation factor-5: pre-clinical and clinical evaluations of periodontal regeneration and alveolar augmentation-review. J Clin Periodontol 2014;41:797-805
107. Li R, Norman RJ, Armstrong DT, Gilchrist RB. Oocyte-secreted factor(s) determine functional differences between bovine mural granulosa cells and cumulus cells. Biol Reprod 2000;63:839-845
108. Li Y, Li RQ, Ou SB, Zhang NF, Ren L, Wei LN, Zhang QX, Yang DZ. Increased GDF9 and BMP15 mRNA levels in cumulus granulosa cells correlate with oocyte maturation, fertilization, and embryo quality in humans. Reprod Biol Endocrinol 2014;12:81
109. Liao WX, Moore RK, Shimasaki S. Functional and molecular characterization of naturally occurring mutations in the oocyte-secreted factors bone morphogenetic protein-15 and growth and differentiation factor-9. J Biol Chem 2004;279:17391-17396
110. Lie BL, Leung E, Leung PC, Auersperg N. Long-term growth and steroidogenic potential of human granulosa-lutein cells immortalized with SV40 large T antigen. Mol Cell Endocrinol 1996;120:169-176
111. Lipson KE, Wong C, Teng Y, Spong S. CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis. Fibrogenesis Tissue Repair 2012;5:S24
112. Lissenberg-Thunnissen SN, de Gorter DJ, Sier CF, Schipper IB. Use and efficacy of bone morphogenetic proteins in fracture healing. Int Orthop 2011;35:1271-1280
113. Little SC, Mullins MC. Bone morphogenetic protein heterodimers assemble heteromeric type I receptor complexes to pattern the dorsoventral axis. Nat Cell Biol 2009;11:637-643
114. Liu J, Wang B, Wei Z, Zhou P, Zu Y, Zhou S, Wen Q, Wang J, Cao Y, Ma X. Mutational analysis of human bone morphogenetic protein 15 in Chinese women with polycystic ovary syndrome. Metabolism 2011;60:1511-1514
115. Macias-Silva M, Hoodless PA, Tang SJ, Buchwald M, Wrana JL. Specific activation of Smad1 signaling pathways by the BMP7 type I receptor, ALK2. J Biol Chem 1998; 273:25628-25636
116. Magoffin DA, Erickson GF. Purification of ovarian theca-interstitial cells by density gradient centrifugation. Endocrinology 1988;122:2345-2347
117. Makowski L, Caspar DL, Phillips WC, Goodenough DA. Gap junction structures. II. Analysis of the x-ray diffraction data. J Cell Biol 1977;74:629-645
118. Margulis S, Abir R, Felz C, Nitke S, Krissi H, Fisch B. Bone morphogenetic protein 15 expression in human ovaries from fetuses, girls, and women. Fertil Steril 2009; 92:1666-1673
119. Massague J. TGF-beta signal transduction. Annu Rev Biochem 1998;67:753-791
120. Mazerbourg S, Hsueh AJ. Genomic analyses facilitate identification of receptors and signalling pathways for growth differentiation factor 9 and related orphan bone morphogenetic protein/growth differentiation factor ligands. Hum Reprod Update 2006;12:373-383
121. McAllister JM, Kerin JF, Trant JM, Estabrook RW, Mason JI, Waterman MR, Simpson ER. Regulation of cholesterol side-chain cleavage and 17 alpha-hydroxylase/lyase activities in proliferating human theca internal cells in long term monolayer culture. Endocrinology 1989;125:1959-1966
122. McGee EA, Hsueh AJ. Initial and cyclic recruitment of ovarian follicles. Endocr Rev 2000;21:200-214
123. 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
124. McLaren A. Primordial germ cells in the mouse. Dev Biol 2003;262:1-15
125. McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 1997;387:83-90
126. McPherron AC, Lee SJ. Double muscling in cattle due to mutations in the myostatin gene. Proc Natl Acad Sci USA 1997;94:12457-12461
127. Miyagi M, Mikawa S, Sato T, Hasegawa T, Kobayashi S, Matsuyama Y, Sato K. BMP2, BMP4, noggin, BMPRIA, BMPRIB, and BMPRII are differentially expressed in the adult rat spinal cord. Neuroscience 2012;203:12-26
128. Miyazono K, Kusanagi K, Inoue H. Divergence and convergence of TGF-beta/BMP signaling. J Cell Physiol 2001;187:265-276
129. Miyoshi T, Otsuka F, Suzuki J, Takeda M, Inagaki K, Kano Y, Otani H, Mimura Y, Ogura T, Makino H. Mutual regulation of follicle-stimulating hormone signaling and bone morphogenetic protein system in human granulosa cells. Biol Reprod 2006;74:1073-1082
130. Moore RK, Otsuka F, Shimasaki S. Molecular basis of bone morphogenetic protein-15 signaling in granulosa cells. J Biol Chem 2003;278:304-310
131. Mosher DS, Quignon P, Bustamante CD, Sutter NB, Mellersh CS, Parker HG, Ostrander EA. A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs. PLoS Genet 2007;3: e79
132. Mottershead DG, Harrison CA, Mueller TD, Stanton PG, Gilchrist RB, McNatty KP. Growth differentiation factor 9:bone morphogenetic protein 15 (GDF9: BMP15) synergism and protein heterodimerization. Proc Natl Acad Sci USA 2013; 110:E2257
133. Mueller TD, Nickel J. Promiscuity and specificity in BMP receptor activation. FEBS Lett 2012;586:1846-1859
134. Nagashima T, Li Q, Clementi C, Lydon JP, DeMayo FJ, Matzuk MM. BMPR2 is required for postimplantation uterine function and pregnancy maintenance. J Clin Invest 2013;123:2539-2550
135. Nakamura K, Shirai T, Morishita S, Uchida S, Saeki-Miura K, Makishima F. p38 mitogen-activated protein kinase functionally contributes to chondrogenesis induced by growth/differentiation factor-5 in ATDC5 cells. Exp Cell Res 1999; 250:351-363
136. Nekola MV, Nalbandov AV. Morphological changes of rat follicular cells as influenced by oocytes. Biol Reprod 1971;4:154-160
137. Nio-Kobayashi J, Trendell J, Giakoumelou S, Boswell L, Nicol L, Kudo M, Sakuragi N, Iwanaga T, Duncan WC. Bone morphogenetic proteins are mediators of luteolysis in the human corpus luteum. Endocrinology 2015;156:1494-1503
138. Nishi Y, Yanase T, Mu Y, Oba K, Ichino I, Saito M, Nomura M, Mukasa C, Okabe T, Goto K et al. Establishment and characterization of a steroidogenic human granulosa-like tumor cell line, KGN, that expresses functional follicle-stimulating hormone receptor. Endocrinology 2001;142:437-445
139. Niswender GD, Juengel JL, Silva PJ, Rollyson MK, McIntush EW. Mechanisms controlling the function and life span of the corpus luteum. Physiol Rev 2000;80:1-29
140. Nitta M, Katabuchi H, Ohtake H, Tashiro H, Yamaizumi M, Okamura H. Characterization and tumorigenicity of human ovarian surface epithelial cells immortalized by SV40 large T antigen. Gynecol Oncol 2001;81:10-17
141. Okamura H, Katabuchi H, Ohba T. What we have learned from isolated cells from human ovary? Mol Cell Endocrinol 2003;202:37-45
142. Oon VJ, Johnson MR. The regulation of the human corpus luteum steroidogenesis: a hypothesis? Hum Reprod Update 2000;6:519-529
143. 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
144. Peiris HN, Salomon C, Payton D, Ashman K, Vaswani K, Chan A, Rice GE, Mitchell MD. Myostatin is localized in extravillous trophoblast and up-regulates migration. J Clin Endocrinol Metab 2014;99:E2288-2297
145. Peng J, Li Q, Wigglesworth K, Rangarajan A, Kattamuri C, Peterson RT, Eppig JJ, Thompson TB, Matzuk MM. Growth differentiation factor 9:bone morphogenetic protein 15 heterodimers are potent regulators of ovarian functions. Proc Natl Acad Sci USA 2013;110:E776-785
146. Pepling ME, Spradling AC. Mouse ovarian germ cell cysts undergo programmed breakdown to form primordial follicles. Dev Biol 2001;234:339-351
147. Persani L, Rossetti R, Cacciatore C. Genes involved in human premature ovarian failure. J Mol Endocrinol 2010;45:257-279
148. Persani L, Rossetti R, Di Pasquale E, Cacciatore C, Fabre S. The fundamental role of bone morphogenetic protein 15 in ovarian function and its involvement in female fertility disorders. Hum Reprod Update 2014;20:869-883
149. Petrocelli T, Lye SJ. Regulation of transcripts encoding the myometrial gap junction protein, connexin-43, by estrogen and progesterone. Endocrinology 1993;133: 284-290
150. Qiao J, Feng HL. Extra-and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence. Hum Reprod Update 2011;17:17-33
151. Qin Y, Jiao X, Simpson JL, Chen ZJ. Genetics of primary ovarian insufficiency: new developments and opportunities. Hum Reprod Update 2015;21:787-808
152. Rainey WH, Sawetawan C, Shay JW, Michael MD, Mathis JM, Kutteh W, Byrd W, Carr BR. Transformation of human granulosa cells with the E6 and E7 regions of human papillomavirus. J Clin Endocrinol Metab 1994;78:705-710
153. Regan SL, Knight PG, Yovich JL, Stanger JD, Leung Y, Arfuso F, Dharmarajan A, Almahbobi G. Dysregulation of granulosal bone morphogenetic protein receptor 1B density is associated with reduced ovarian reserve and the age-related decline in human fertility. Mol Cell Endocrinol 2016;425:84-93
154. Rider CC, Mulloy B. Bone morphogenetic protein and growth differentiation factor cytokine families and their protein antagonists. Biochem J 2010;429:1-12
155. Rossi RO, Costa JJ, Silva AW, Saraiva MV, Van den Hurk R, Silva JR. The bone morphogenetic protein system and the regulation of ovarian follicle development in mammals. Zygote 2016;24:1-17
156. Russell DL, Robker RL. Molecular mechanisms of ovulation: co-ordination through the cumulus complex. Hum Reprod Update 2007;13:289-312
157. Russell DL, Salustri A. Extracellular matrix of the cumulus-oocyte complex. Semin Reprod Med 2006;24:217-227
158. Salustri A, Ulisse S, Yanagishita M, Hascall VC. Hyaluronic acid synthesis by mural granulosa cells and cumulus cells in vitro is selectively stimulated by a factor produced by oocytes and by transforming growth factor-beta. J Biol Chem 1990;265: 19517-19523
159. Schmidt-Bleek K, Willie BM, Schwabe P, Seemann P, Duda GN. BMPs in bone regeneration: less is more effective, a paradigm-shift. Cytokine Growth Factor Rev 2016;27:141-148
160. Schuelke M, Wagner KR, Stolz LE, Hubner C, Riebel T, Komen W, Braun T, Tobin JF, Lee SJ. Myostatin mutation associated with gross muscle hypertrophy in a child. N Engl J Med 2004;350:2682-2688
161. Seidah NG, Prat A. The biology and therapeutic targeting of the proprotein convertases. Nat Rev Drug Discov 2012;11:367-383
162. Sherman ML, Borgstein NG, Mook L, Wilson D, Yang Y, Chen N, Kumar R, Kim K, Laadem A. Multiple-dose, safety, pharmacokinetic, and pharmacodynamic study of sotatercept (ActRIIA-IgG1), a novel erythropoietic agent, in healthy postmenopausal women. J Clin Pharmacol 2013;53:1121-1130
163. Shi FT, Cheung AP, Huang HF, Leung PC. Effects of endogenous growth differentiation factor 9 on activin A-induced inhibin B production in human granulosalutein cells. J Clin Endocrinol Metab 2009;94:5108-5116
164. Shi FT, Cheung AP, Klausen C, Huang HF, Leung PC. Growth differentiation factor 9 reverses activin A suppression of steroidogenic acute regulatory protein expression and progesterone production in human granulosa-lutein cells. J Clin Endocrinol Metab 2010;95:E172-180
165. Shi J, Yoshino O, Osuga Y, Koga K, Hirota Y, Nose E, Nishii O, Yano T, Taketani Y. Bone morphogenetic protein-2 (BMP-2) increases gene expression of FSH receptor and aromatase and decreases gene expression of LH receptor and StAR in human granulosa cells. Am J Reprod Immunol 2011;65:421-427
166. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 2003;113:685-700
167. Shimasaki S, Moore RK, Otsuka F, Erickson GF. The bone morphogenetic protein system in mammalian reproduction. Endocr Rev 2004;25:72-101
168. Shimasaki S, Zachow RJ, Li D, Kim H, Iemura S, 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
169. Simon AM, Goodenough DA, Li E, Paul DL. Female infertility in mice lacking connexin 37. Nature 1997;385:525-529
170. Simpson CM, Robertson DM, Al-Musawi SL, Heath DA, McNatty KP, Ritter LJ, Mottershead DG, Gilchrist RB, Harrison CA, Stanton PG. Aberrant GDF9 expression and activation are associated with common human ovarian disorders. J Clin Endocrinol Metab 2014;99:E615-624
171. Skinner MK, Schmidt M, Savenkova MI, Sadler-Riggleman I, Nilsson EE. Regulation of granulosa and theca cell transcriptomes during ovarian antral follicle development. Mol Reprod Dev 2008;75:1457-1472
172. Smith RC, Lin BK. Myostatin inhibitors as therapies for muscle wasting associated with cancer and other disorders. Curr Opin Support Palliat Care 2013;7:352-360
173. Spiekerkoetter E, Tian X, Cai J, Hopper RK, Sudheendra D, Li CG, El-Bizri N, Sawada H, Haghighat R, Chan R et al. FK506 activates BMPR2, rescues endothelial dysfunction, and reverses pulmonary hypertension. J Clin Invest 2013;123: 3600-3613
174. Sugiura K, Su YQ, Eppig JJ. Does bone morphogenetic protein 6 (BMP6) affect female fertility in the mouse? Biol Reprod 2010;83:997-1004
175. Sugiyama R, Fuzitou A, Takahashi C, Akutagawa O, Ito H, Nakagawa K, Sugiyama R, Isaka K. Bone morphogenetic protein 2 may be a good predictor of success in oocyte fertilization during assisted reproductive technology. Hum Cell 2010;23: 83-88
176. Sun PD, Davies DR. The cystine-knot growth-factor superfamily. Annu Rev Biophys Biomol Struct 1995;24:269-291
177. Tajima K, Hosokawa K, Yoshida Y, Dantes A, Sasson R, Kotsuji F, Amsterdam A. Establishment of FSH-responsive cell lines by transfection of pre-ovulatory human granulosa cells with mutated p53 (p53val135) and Ha-ras genes. Mol Hum Reprod 2002;8:48-57
178. Takebayashi K, Takakura K, Wang H, Kimura F, Kasahara K, Noda Y. Mutation analysis of the growth differentiation factor-9 and-9B genes in patients with premature ovarian failure and polycystic ovary syndrome. Fertil Steril 2000;74: 976-979
179. Teixeira Filho FL, Baracat EC, Lee TH, Suh CS, Matsui M, Chang RJ, Shimasaki S, Erickson GF. Aberrant expression of growth differentiation factor-9 in oocytes of women with polycystic ovary syndrome. J Clin Endocrinol Metab 2002;87: 1337-1344
180. Tiotiu D, Alvaro Mercadal B, Imbert R, Verbist J, Demeestere I, De Leener A, Englert Y, Vassart G, Costagliola S, Delbaere A. Variants of the BMP15 gene in a cohort of patients with premature ovarian failure. Hum Reprod 2010;25:1581-1587
181. Tsai MY, Lan KC, Huang KE, Huang FJ, Kung FT, Chang SY. Significance of mRNA levels of connexin37, connexin43, and connexin45 in luteinized granulosa cells of controlled hyperstimulated follicles. Fertil Steril 2003;80:1437-1443
182. Valera E, Isaacs MJ, Kawakami Y, Izpisua Belmonte JC, Choe S. BMP-2/6 heterodimer is more effective than BMP-2 or BMP-6 homodimers as inductor of differentiation of human embryonic stem cells. PLoS One 2010;5:e11167
183. van den Berg-Bakker CA, Hagemeijer A, Franken-Postma EM, Smit VT, Kuppen PJ, van Ravenswaay Claasen HH, Cornelisse CJ, Schrier PI. Establishment and characterization of 7 ovarian carcinoma cell lines and one granulosa tumor cell line: growth features and cytogenetics. Int J Cancer 1993;53:613-620
184. van Houten EL, Laven JS, Louwers YV, McLuskey A, Themmen AP, Visser JA. Bone morphogenetic proteins and the polycystic ovary syndrome. J Ovarian Res 2013; 6:32
185. Vanderhyden BC. Species differences in the regulation of cumulus expansion by an oocyte-secreted factor(s). J Reprod Fertil 1993;98:219-227
186. Vanderhyden BC, Armstrong DT. Role of cumulus cells and serum on the in vitro maturation, fertilization, and subsequent development of rat oocytes. Biol Reprod 1989;40:720-728
187. Vanderhyden BC, Telfer EE, Eppig JJ. Mouse oocytes promote proliferation of granulosa cells from preantral and antral follicles in vitro. Biol Reprod 1992;46: 1196-1204
188. Vanderhyden BC, Tonary AM. Differential regulation of progesterone and estradiol production by mouse cumulus and mural granulosa cells by A factor(s) secreted by the oocyte. Biol Reprod 1995;53:1243-1250
189. Varani S, Elvin JA, Yan C, DeMayo J, DeMayo FJ, Horton HF, Byrne MC, Matzuk MM. Knockout of pentraxin 3, a downstream target of growth differentiation factor-9, causes female subfertility. Mol Endocrinol 2002;16:1154-1167
190. Veitia RA, Caburet S. Extensive sequence turnover of the signal peptides of members of the GDF/BMP family: exploring their evolutionary landscape. Biol Direct 2009;4:22
191. Vigano P, Parazzini F, Somigliana E, Vercellini P. Endometriosis: epidemiology and aetiological factors. Best Pract Res Clin Obstet Gynaecol 2004;18:177-200
192. von BubnoffA, Cho KW. Intracellular BMP signaling regulation in vertebrates: pathway or network? Dev Biol 2001;239:1-14
193. Wagner DO, Sieber C, Bhushan R, Borgermann JH, Graf D, Knaus P. BMPs: from bone to body morphogenetic proteins. Sci Signal 2010;3:mr1
194. Wang EA, Rosen V, Cordes P, Hewick RM, Kriz MJ, Luxenberg DP, Sibley BS, Wozney JM. Purification and characterization of other distinct bone-inducing factors. Proc Natl Acad Sci USA 1988;85:9484-9488
195. Wang TT, Ke ZH, Song Y, Chen LT, Chen XJ, Feng C, Zhang D, Zhang RJ, Wu YT, Zhang Y et al. Identification of a mutation in GDF9 as a novel cause of diminished ovarian reserve in young women. Hum Reprod 2013;28:2473-2481
196. Wang Y, Ho CC, Bang E, Rejon CA, Libasci V, Pertchenko P, Hebert TE, Bernard DJ. Bone morphogenetic protein 2 stimulates noncanonical SMAD2/3 signaling via the BMP type 1A receptor in gonadotrope-like cells: implications for FSH synthesis. Endocrinology 2014;155:1970-1981
197. Wei LN, Huang R, Li LL, Fang C, Li Y, Liang XY. Reduced and delayed expression of GDF9 and BMP15 in ovarian tissues from women with polycystic ovary syndrome. J Assist Reprod Genet 2014;31:1483-1490
198. Weigel PH, Hascall VC, Tammi M. Hyaluronan synthases. J Biol Chem 1997;272: 13997-14000
199. Wigglesworth K, Lee KB, Emori C, Sugiura K, Eppig JJ. Transcriptomic diversification of developing cumulus and mural granulosa cells in mouse ovarian follicles. Biol Reprod 2015;92:23
200. WoodruffTK, Shea LD. The role of the extracellular matrix in ovarian follicle development. Reprod Sci 2007;14:6-10
201. Wu CH, Yang JG, Yang JJ, Lin YM, Tsai HD, Lin CY, Kuo PL. Androgen excess down-regulates connexin43 in a human granulosa cell line. Fertil Steril 2010;94: 2938-2941
202. Wu YT, Tang L, Cai J, Lu XE, Xu J, Zhu XM, Luo Q, Huang HF. High bone morphogenetic protein-15 level in follicular fluid is associated with high quality oocyte and subsequent embryonic development. Hum Reprod 2007;22:1526-1531
203. Wu YT, Wang TT, Chen XJ, Zhu XM, Dong MY, Sheng JZ, Xu CM, Huang HF. Bone morphogenetic protein-15 in follicle fluid combined with age may differentiate between successful and unsuccessful poor ovarian responders. Reprod Biol Endocrinol 2012;10:116
204. Yamaguchi K, Shirakabe K, Shibuya H, Irie K, Oishi I, Ueno N, Taniguchi T, Nishida E, Matsumoto K. Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction. Science 1995;270:2008-2011
205. Yamamoto N, Christenson LK, McAllister JM, Strauss JF III. Growth differentiation factor-9 inhibits 3'5'-adenosine monophosphate-stimulated steroidogenesis in human granulosa and theca cells. J Clin Endocrinol Metab 2002;87: 2849-2856
206. 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;15:854-866
207. Yi SE, LaPolt PS, Yoon BS, Chen JY, Lu JK, Lyons KM. The type I BMP receptor BmprIB is essential for female reproductive function. Proc Natl Acad Sci USA 2001;98:7994-7999
208. Ying Y, Qi X, Zhao GQ. Induction of primordial germ cells from pluripotent epiblast. Sci World J 2002;2:801-810
209. Zhang H, Klausen C, Zhu H, Chang HM, Leung PC. BMP4 and BMP7 suppress StAR and progesterone production via ALK3 and SMAD1/5/8-SMAD4 in human granulosa-lutein cells. Endocrinology 2015;156:4269-4280
210. Zhang H, Tian S, Klausen C, Zhu H, Liu R, Leung PC. Differential activation of noncanonical SMAD2/SMAD3 signaling by bone morphogenetic proteins causes disproportionate induction of hyaluronan production in immortalized human granulosa cells. Mol Cell Endocrinol 2016;428:17-27
211. Zhang H, Vollmer M, De Geyter M, Litzistorf Y, Ladewig A, Durrenberger M, Guggenheim R, Miny P, Holzgreve W, De Geyter C. Characterization of an immortalized human granulosa cell line (COV434). Mol Hum Reprod 2000;6:146-153
212. Zhang X, Jafari N, Barnes RB, Confino E, Milad M, Kazer RR. Studies of gene expression in human cumulus cells indicate pentraxin 3 as a possible marker for oocyte quality. Fertil Steril 2005;83:1169-1179
213. Zhao SY, Qiao J, Chen YJ, Liu P, Li J, Yan J. Expression of growth differentiation factor-9 and bone morphogenetic protein-15 in oocytes and cumulus granulosa cells of patients with polycystic ovary syndrome. Fertil Steril 2010;94: 261-267