Browse > Article
http://dx.doi.org/10.5713/ajas.15.0797

Role of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Ovarian Function and Their Importance in Mammalian Female Fertility - A Review  

Castro, Fernanda Cavallari de (Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of Sao Paulo)
Cruz, Maria Helena Coelho (Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of Sao Paulo)
Leal, Claudia Lima Verde (Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of Sao Paulo)
Publication Information
Asian-Australasian Journal of Animal Sciences / v.29, no.8, 2016 , pp. 1065-1074 More about this Journal
Abstract
Growth factors play an important role during early ovarian development and folliculogenesis, since they regulate the migration of germ cells to the gonadal ridge. They also act on follicle recruitment, proliferation/atresia of granulosa cells and theca, steroidogenesis, oocyte maturation, ovulation and luteinization. Among the growth factors, the growth differentiation factor 9 (GDF9) and the bone morphogenetic protein 15 (BMP15), belong to the transforming growth factor beta (TGF-${\beta}$) superfamily, have been implicated as essential for follicular development. The GDF9 and BMP15 participate in the evolution of the primordial follicle to primary follicle and play an important role in the later stages of follicular development and maturation, increasing the steroidogenic acute regulatory protein expression, plasminogen activator and luteinizing hormone receptor (LHR). These factors are also involved in the interconnections between the oocyte and surrounding cumulus cells, where they regulate absorption of amino acids, glycolysis and biosynthesis of cholesterol cumulus cells. Even though the mode of action has not been fully established, in vitro observations indicate that the factors GDF9 and BMP15 stimulate the growth of ovarian follicles and proliferation of cumulus cells through the induction of mitosis in cells and granulosa and theca expression of genes linked to follicular maturation. Thus, seeking greater understanding of the action of these growth factors on the development of oocytes, the role of GDF9 and BMP15 in ovarian function is summarized in this brief review.
Keywords
Cumulus Cells; Granulosa Cells; Oocyte Maturation; Follicular Development; Reproductive Efficiency; TGF-${\beta}$ Superfamily;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Vitt, U. A., M. Hayashi, C. Klein, and A. J. Hsueh. 2000a. Growth differentiation factor-9 stimulates proliferation but suppresses the follicle-stimulating hormone-induced differentiation of cultured granulosa cells from small antral and preovulatory rat follicles. Biol. Reprod. 62:370-377.   DOI
2 Vitt, U. A., E. A. McGee, M. Hayashi, and A. J. W. Hsueh. 2000b. In vivo treatment with GDF-9 stimulates primordial and primary follicle progression and theca cell marker CYP17 in ovaries of immature rats. Endocrinology 141:3814-3820.   DOI
3 Vitt, U. A., S. Mazerbourg, C. Klein, and A. J. W. Hsueh. 2002. Bone morphogenetic protein receptor type II is a receptor for growth differentiation factor-9. Biol. Reprod. 67:473-480.   DOI
4 Webb, R., B. Nicholas, J. G. Gong, B. K. Campbell, C. G. Gutierrez, H. A. Garverick, and D. G. Armstrong. 2003. Mechanisms regulating follicular development and selection of the dominant follicle. Reprod. Suppl. 61:71-90.
5 Wigglesworth, K., K.-B. Lee, M. J. O'Brien, J. Peng, M. M. Matzuk, and J. J. Eppig. 2013. Bidirectional communication between oocytes and ovarian follicular somatic cells is required for meiotic arrest of mammalian oocytes. Proc. Natl. Acad. Sci. USA. 110:E3723-E3729.   DOI
6 Yan, C., P. Wang, J. DeMayo, F. J. DeMayo, J. A. Elvin, C. Carino, S. V Prasad, S. S. Skinner, B. S. Dunbar, J. L. Dube, A. J. Celeste, and M. M. Matzuk. 2001. Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Mol. Endocrinol. 15:854-866.   DOI
7 Yeo, C. X., R. B. Gilchrist, J. G. Thompson, and M. Lane. 2008. Exogenous growth differentiation factor 9 in oocyte maturation media enhances subsequent embryo development and fetal viability in mice. Hum. Reprod. 23:67-73.
8 Aaltonen, J., M. P. Laitinen, K. Vuojolainen, R. Jaatinen, N. Horelli-Kuitunen, L. Seppa, H. Louhio, T. Tuuri, J. Sjoberg, R. Butzow, O. Hovatta, L. Dale, and O. Ritvos. 1999. Human growth differentiation factor 9 (GDF-9) and its novel homolog GDF-9B are expressed in oocytes during early folliculogenesis. J. Clin. Endocrinol. Metab. 84:2744-2750.
9 Yoshino, O., H. E. McMahon, S. Sharma, and S. Shimasaki. 2006. A unique preovulatory expression pattern plays a key role in the physiological functions of BMP-15 in the mouse. Proc. Natl. Acad. Sci. USA. 103:10678-10683.   DOI
10 Ying, Y., X. M. Liu, A. Marble, K. A. Lawson, and G. Q. Zhao. 2000. Requirement of Bmp8b for the generation of primordial germ cells in the mouse. Mol. Endocrinol. 14:1053-1063.   DOI
11 Young, J. M. and A. S. McNeilly. 2010. Theca: The forgotten cell of the ovarian follicle. Reproduction 140:489-504.   DOI
12 Zhao, H., Y. Qin, E. Kovanci, J. L. Simpson, Z.-J. Chen, and A. Rajkovic. 2007. Analyses of GDF9 mutation in 100 Chinese women with premature ovarian failure. Fertil. Steril. 88:1474-1476.   DOI
13 Araujo, V. R., A. P. Almeida, D. M. Magalhaes, M. H. T. Matos, L. M. T. Tavares, J. R. Figueiredo, and A. P. R. Rodrigues. 2010. Role of Bone Morphogenetic Proteins-6 and -7 (BMP-6 and - 7) in the regulation of early foliculogenesis in mammals. Rev. Bras. Reproducao Anim. 34:69-78.
14 Aerts, J. M. J. and P. E. J. Bols. 2010. Ovarian follicular dynamics: A review with emphasis on the bovine species. Part I: Folliculogenesis and pre-antral follicle development. Reprod. Domest. Anim. 45:171-179.   DOI
15 Albertini, D. F., C. M. H. Combelles, E. Benecchi, and M. J. Carabatsos. 2001. Cellular basis for paracrine regulation of ovarian follicle development. Reproduction 121:647-653.   DOI
16 Anderson, E. and D. F. Albertini. 1976. Gap junctions between the oocyte and companion follicle cells in the mammalian ovary. J. Cell Biol. 71:680-686.   DOI
17 Armstrong, D. T., P. Xia, G. Gannes, F. R. Tekpetey, and F. Khamsi. 1996. 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. 54:331-338.   DOI
18 Bodensteiner, K. J., C. M. Clay, C. L. Moeller, and H. R. Sawyer. 1999. Molecular cloning of the ovine Growth/Differentiation factor-9 gene and expression of growth/differentiation factor-9 in ovine and bovine ovaries. Biol. Reprod. 60:381-386.   DOI
19 Buratini Jr, J. 2007. Endocrine and local control of folliculogenesis in cattle. Rev. Bras. Reproducao Anim. 31:190-196.
20 Caixeta, E. S. 2012. Regulation of Expression of Oocyte Secreted Factors (OSFs) and Their Receptors during Bovine In vitio Maturation (IVM) and Actions in the Control of Cumulus Expansion. Ph.D. Thesis, University of Sao Paulo State, Botucatu, Sao Paulo, Brazil.
21 Chang, H., C. W. Brown, and M. M. Matzuk. 2002. Genetic analysis of the mammalian transforming growth factor-${\beta}$ superfamily. Endocr. Rev. 23:787-823.   DOI
22 Campos, C. O., A. A. Vireque, J. R. Campos, and A. C. J. S. R. Silva. 2011. The influence of interaction between oocyte and granulosa cells on the results of procedures in assisted reproduction. Femina 39:207-216.
23 Carabatsos, M. J., J. Elvin, M. M. Matzuk, and D. F. Albertini. 1998. Characterization of oocyte and follicle development in growth differentiation factor-9-deficient mice. Dev. Biol. 204:373-384.   DOI
24 Ceko, M. J., K. Hummitzsch, N. Hatzirodos, W. M. Bonner, J. B. Aitken, D. L. Russell, M. Lane, R. J. Rodgers, and H. H. Harris. 2015. X-Ray fluorescence imaging and other analyses identify selenium and GPX1 as important in female reproductive function. Metallomics 7:71-82.   DOI
25 Derynck, R. 1998. Developmental biology: SMAD proteins and mammalian anatomy. Nature 393:737-739.   DOI
26 Di Pasquale, E., P. Beck-Peccoz, and L. Persani. 2004. Hypergonadotropic ovarian failure associated with an inherited mutation of human bone morphogenetic protein-15 (BMP15) gene. Am. J. Hum. Genet. 75:106-111.   DOI
27 Dias, F. C. F., M. I. R. Khan, G. P. Adams, M. A. Sirard, and J. Singh. 2014. Granulosa cell function and oocyte competence: Super-follicles, super-moms and super-stimulation in cattle. Anim. Reprod. Sci. 149:80-89.   DOI
28 Dixit, H., L. K. Rao, V. V. Padmalatha, M. Kanakavalli, M. Deenadayal, N. Gupta, B. Chakrabarty, and L. Singh. 2006. Missense mutations in the BMP15 gene are associated with ovarian failure. Hum. Genet. 119:408-415.   DOI
29 Dube, J. L., P. Wang, J. Elvin, K. M. Lyons, A. J. Celeste, and M. M. Matzuk. 1998. The bone morphogenetic protein 15 gene is X-linked and expressed in oocytes. Mol. Endocrinol. (Baltimore, Md.). 12:1809-1817.   DOI
30 Dong, J., D. F. Albertini, K. Nishimori, T. R. Kumar, N. Lu, and M. M. Matzuk. 1996. Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 383:531-535.   DOI
31 Eckery, D. C., L. J. Whale, S. B. Lawrence, K. A. Wylde, K. P. McNatty, and J. L. Juengel. 2002. 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. 192:115-126.   DOI
32 Edson, M. A., A. K. Nagaraja, and M. M. Matzuk. 2009. The mammalian ovary from genesis to revelation. Endocr. Rev. 30:624-712.   DOI
33 Elvin, J. A., C. Yan, and M. M. Matzuk. 2000. Oocyte-expressed TGF-${\beta}$ superfamily members in female fertility. Mol. Cell. Endocrinol. 159:1-5.   DOI
34 Elvin, J. A., A. T. Clark, P. Wang, N. M. Wolfman, and M. M. Matzuk. 1999. Paracrine actions of growth differentiation factor-9 in the mammalian ovary. Mol. Endocrinol. (Baltimore, Md.). 13:1035-1048.   DOI
35 Eppig, J. J. 2001. Oocyte control of ovarian follicular development and function in mammals. Reproduction 122:829-838.   DOI
36 Eppig, J. J., K. Wigglesworth, and F. L. Pendola. 2002. The mammalian oocyte orchestrates the rate of ovarian follicular development. Proc. Natl. Acad. Sci. USA. 99:2890-2894.   DOI
37 Fair, T. 2003. Follicular oocyte growth and acquisition of developmental competence. Anim. Reprod. Sci. 78:203-216.   DOI
38 Eppig, J. J., K. Wigglesworth, F. Pendola, and Y. Hirao. 1997. Murine oocytes suppress expression of luteinizing hormone receptor messenger ribonucleic acid by granulosa cells. Biol. Reprod. 56:976-984.   DOI
39 Eppig, J. J., M. J. O'Brien, F. L. Pendola, and S. Watanabe. 1998. Factors affecting the developmental competence of mouse oocytes grown in vitro: Follicle-stimulating hormone and insulin. Biol. Reprod. 59:1445-1453.   DOI
40 Eppig, J. J., F. L. Pendola, K. Wigglesworth, and J. K. Pendola. 2005. Mouse oocytes regulate metabolic cooperativity between granulosa cells and oocytes: Amino acid transport. Biol. Reprod. 73:351-357.   DOI
41 Fair, T. 2013. Molecular and endocrine determinants of oocyte competence. Anim. Reprod. 10:277-282.
42 Franzen, P., P. ten Dijke, H. Ichijo, H. Yamashita, P. Schulz, C. H. Heldin, and K. Miyazono. 1993. Cloning of a TGF beta type I receptor that forms a heteromeric complex with the TGF beta type II receptor. Cell 75:681-692.   DOI
43 Galloway, S. M., K. P. McNatty, L. M. Cambridge, M. P. Laitinen, J. L. Juengel, T. S. Jokiranta, R. J. McLaren, K. Luiro, K. G. Dodds, G. W. Montgomery, A. E. Beattie, G. H. Davis, and O. Ritvos. 2000. Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nat. Genet. 25:279-283.   DOI
44 Gandolfi, F., T. A. L. Brevini, F. Cillo, and S. Antonini. 2005. Cellular and molecular mechanisms regulating oocyte quality and the relevance for farm animal reproductive efficiency. Rev. Sci. Tech. 24:413-23.   DOI
45 Gittens, J. E. I., K. J. Barr, B. C. Vanderhyden, and G. M. Kidder. 2005. Interplay between paracrine signaling and gap junctional communication in ovarian follicles. J. Cell Sci. 118:113-122.   DOI
46 Gilchrist, R. B., L. J. Ritter, and D. T. Armstrong. 2004. Oocyte-somatic cell interactions during follicle development in mammals. Anim. Reprod. Sci. 82-83:431-446.   DOI
47 Gilchrist, R. B., M. Lane, and J. G. Thompson. 2008. Oocyte-secreted factors: Regulators of cumulus cell function and oocyte quality. Hum. Reprod. Update 14:159-177.   DOI
48 Gilchrist, R. B., L. J. Ritter, S. Myllymaa, N. Kaivo-Oja, R. A. Dragovic, T. E. Hickey, O. Ritvos, and D. G. Mottershead. 2006. Molecular basis of oocyte-paracrine signalling that promotes granulosa cell proliferation. J. Cell Sci. 119:3811-3821.   DOI
49 Gottardi, F. P. and G. Z. Mingoti. 2010. Bovine oocyte maturation and influence on subsequent embryonic developmental competence. Rev. Bras. Reprod. Anim. 33:82-94.
50 Gueripel, X., V. Brun, and A. Gougeon. 2006. Oocyte bone morphogenetic protein 15, but not growth differentiation factor 9, is increased during gonadotropin-induced follicular development in the immature mouse and is associated with cumulus oophorus expansion. Biol. Reprod. 75:836-843.   DOI
51 Gui, L.-M. and I. M. Joyce. 2005. RNA interference evidence that growth differentiation factor-9 mediates oocyte regulation of cumulus expansion in mice. Biol. Reprod. 72:195-199.   DOI
52 Hanrahan, J. P., S. M. Gregan, P. Mulsant, M. Mullen, G. H. Davis, R. Powell, and S. M. Galloway. 2004. Mutations in the genes for oocyte-derived growth factors GDF9 and BMP15 are associated with both increased ovulation rate and sterility in Cambridge and Belclare sheep (Ovis aries). Biol. Reprod. 70:900-909.   DOI
53 Hennet, M. L. and C. M. H. Combelles. 2012. The antral follicle: A microenvironment for oocyte differentiation. Int. J. Dev. Biol. 56:819-831.   DOI
54 Hatzirodos, N., H. F. Irving-Rodgers, K. Hummitzsch, M. L. Harland, S. E. Morris, and R. J. Rodgers. 2014. Transcriptome profiling of granulosa cells of bovine ovarian follicles during growth from small to large antral sizes. BMC Genomics 15:24.   DOI
55 Hayashi, M., E. A. McGee, G. Min, C. Klein, U. M. Rose, M. Van Duin, and A. J. W. Hsueh. 1999. Recombinant growth differentiation factor-9 (GDF-9) enhances growth and differentiation of cultured early ovarian follicles. Endocrinology 140:1236-1244.   DOI
56 Heldin, C.-H., K. Miyazono, and P. ten Dijke. 1997. TGF-bold beta signalling from cell membrane to nucleus through SMAD proteins. Nature 390:465-471.   DOI
57 Hickey, T. E., D. L. Marrocco, R. B. Gilchrist, R. J. Norman, and D. T. Armstrong. 2004. Interactions between androgen and growth factors in granulosa cell subtypes of porcine antral follicles. Biol. Reprod. 71:45-52.   DOI
58 Hoekstra, C., Z. Z. Zhao, C. B. Lambalk, G. Willemsen, N. G. Martin, D. I. Boomsma, and G. W. Montgomery. 2008. Dizygotic twinning. Hum. Reprod. Update 14:37-47.   DOI
59 Huang, Q., A. P. Cheung, Y. Zhang, H.-F. Huang, N. Auersperg, and P. C. K. Leung. 2009. Effects of growth differentiation factor 9 on cell cycle regulators and ERK42/44 in human granulosa cell proliferation. Am. J. Physiol. Endocrinol. Metab. 296:E1344-E1353.   DOI
60 Hussein, T. S., J. G. Thompson, and R. B. Gilchrist. 2006. Oocyte-secreted factors enhance oocyte developmental competence. Dev. Biol. 296:514-521.   DOI
61 Inagaki, K. and S. Shimasaki. 2010. Impaired production of BMP-15 and GDF-9 mature proteins derived from proproteins WITH mutations in the proregion. Mol. Cell. Endocrinol. 328:1-7.   DOI
62 Hussein, T. S., M. L. Sutton-McDowall, R. B. Gilchrist, and J. G. Thompson. 2011. Temporal effects of exogenous oocyte-secreted factors on bovine oocyte developmental competence during IVM. Reprod. Fertil. Dev. 23:576-584.   DOI
63 Hussein, T. S., D. A. Froiland, F. Amato, J. G. Thompson, and R. B. Gilchrist. 2005. Oocytes prevent cumulus cell apoptosis by maintaining a morphogenic paracrine gradient of bone morphogenetic proteins. J. Cell Sci. 118:5257-5268.   DOI
64 Hutt, K. J. and D. F. Albertini. 2007. An oocentric view of folliculogenesis and embryogenesis. Reprod. Biomed. Online 14:758-764.   DOI
65 Jaatinen, R., M. P. Laitinen, K. Vuojolainen, J. Aaltonen, H. Louhio, K. Heikinheimo, E. Lehtonen, and O. Ritvos. 1999. 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. 156:189-193.   DOI
66 Juengel, J. L., K. J. Bodensteiner, D. A. Heath, N. L. Hudson, C. L. Moeller, P. Smith, S. M. Galloway, G. H. Davis, H. R. Sawyer, and K. P. McNatty. 2004a. Physiology of GDF9 and BMP15 signalling molecules. Anim. Reprod. Sci. 82-83:447-460.   DOI
67 Juengel, J. L., N. L. Hudson, D. A. Heath, P. Smith, K. L. Reader, S. B. Lawrence, A. R. O'Connell, M. P. E. Laitinen, M. Cranfield, N. P. Groome, O. Ritvos, and K. P. McNatty. 2002. Growth differentiation factor 9 and bone morphogenetic protein 15 are essential for ovarian follicular development in sheep. Biol. Reprod. 67:1777-1789.   DOI
68 Juengel, J. L., A. H. Bibby, K. L. Reader, S. Lun, L. D. Quirke, L. J. Haydon, and K. P. McNatty. 2004b. The role of transforming growth factor-beta (TGF-beta) during ovarian follicular development in sheep. Reprod. Biol. Endocrinol. 2:78.   DOI
69 Juengel, J. L. and K. P. McNatty. 2005. The role of proteins of the transforming growth factor-${\beta}$ superfamily in the intraovarian regulation of follicular development. Hum. Reprod. Update 11:144-161.   DOI
70 Juengel, J. L., G. H. Davis, and K. P. McNatty. 2013. Using sheep lines with mutations in single genes to better understand ovarian function. Reproduction 146:R111-R123.   DOI
71 Laissue, P., S. Christin-Maitre, P. Touraine, F. Kuttenn, O. Ritvos, K. Aittomaki, N. Bourcigaux, L. Jacquesson, P. Bouchard, R. Frydman, D. Dewailly, A. C. Reyss, L. Jeffery, A. Bachelot, N. Massin, M. Fellous, and R. A. Veitia. 2006. Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure. Eur. J. Endocrinol. 154:739-744.   DOI
72 Laitinen, M., K. Vuojolainen, R. Jaatinen, I. Ketola, J. Aaltonen, E. Lehtonen, M. Heikinheimo, and O. Ritvos. 1998. A novel growth differentiation factor-9 (GDF-9) related factor is co-expressed with GDF-9 in mouse oocytes during folliculogenesis. Mech. Dev. 78:135-140.   DOI
73 Lan, Z. J., P. Gu, X. Xu, K. J. Jackson, F. J. DeMayo, B. W. O'Malley, and A. J. Cooney. 2003. GCNF-dependent repression of BMP-15 and GDF-9 mediates gamete regulation of female fertility. EMBO J. 22:4070-4081.   DOI
74 Li, H.-K., T.-Y. Kuo, H.-S. Yang, L.-R. Chen, S. S.-L. Li, and H.-W. Huang. 2008a. Differential gene expression of bone morphogenetic protein 15 and growth differentiation factor 9 during in vitro maturation of porcine oocytes and early embryos. Anim. Reprod. Sci. 103:312-322.   DOI
75 Lima, R. S. 2012. The Role of Insulin-like Growth Factor-I on Germinal Vesicle Oocytes Exposed to Heat Shock. Masters Dissertation, University of Sao Paulo State, Campus of Botucatu, Sao Paulo, Brazil.
76 Li, Q., L. J. McKenzie, and M. M. Matzuk. 2008b. Revisiting oocyte-somatic cell interactions: In search of novel intrafollicular predictors and regulators of oocyte developmental competence. Mol. Hum. Reprod. 14:673-678.   DOI
77 Li, Q., S. Rajanahally, M. A. Edson, and M. M. Matzuk. 2009. Stable expression and characterization of N-terminal tagged recombinant human bone morphogenetic protein 15. Mol. Hum. Reprod. 15:779-788.   DOI
78 Lima, I. M. T., J. R. Celestino, J. R. Figueiredo, and A. P. R. Rodrigues. 2010. Role of Bone Morphogenetic Protein 15 (BMP-15) and Kit Ligand (KL) in the regulation of folliculogenesis in mammalian. Rev. Bras. Reproducao Anim. 34:3-20.
79 Matzuk, M. M. and K. H. Burns. 2012. Genetics of mammalian reproduction: Modeling the end of the germline. Annu. Rev. Physiol. 74:503-528.   DOI
80 Matzuk, M. M., K. H. Burns, M. M. Viveiros, and J. J. Eppig. 2002. Intercellular communication in the mammalian ovary: oocytes carry the conversation. Science 296:2178-2180.   DOI
81 Mazerbourg, S. and A. J. W. Hsueh. 2006. 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 12:373-383.   DOI
82 Mazerbourg, S., C. Klein, J. Roh, N. Kaivo-Oja, D. G. Mottershead, O. Korchynskyi, O. Ritvos, and A. J. W. Hsueh. 2004. Growth differentiation factor-9 signaling is mediated by the type I receptor, activin receptor-like kinase 5. Mol. Endocrinol. 18:653-665.   DOI
83 McNatty, K. P., L. G. Moore, N. L. Hudson, L. D. Quirke, S. B. Lawrence, K. Reader, J. P. Hanrahan, P. Smith, N. P. Groome, M. Laitinen, O. Ritvos, and J. L. Juengel. 2004. The oocyte and its role in regulating ovulation rate: A new paradigm in reproductive biology. Reproduction 128:379-386.   DOI
84 McGrath, S. A., A. F. Esquela, and S. J. Lee. 1995. Oocyte-specific expression of growth/differentiation factor-9. Mol. Endocrinol. 9:131-136.
85 McNatty, K. P., P. Smith, L. G. Moore, K. Reader, S. Lun, J. P. Hanrahan, N. P. Groome, M. Laitinen, O. Ritvos, and J. L. Juengel. 2005a. Oocyte-expressed genes affecting ovulation rate. Mol. Cell. Endocrinol. 234:57-66.   DOI
86 McNatty, K. P., S. M. Galloway, T. Wilson, P. Smith, N. L. Hudson, A. O'Connell, A. H. Bibby, D. A. Heath, G. H. Davis, J. P. Hanrahan, and J. L. Juengel. 2005b. Physiological effects of major genes affecting ovulation rate in sheep. Genet. Sel. Evol. 37:S25-38.   DOI
87 McNatty, K. P., J. L. Juengel, K. L. Reader, S. Lun, S. Myllymaa, S. B. Lawrence, A. Western, M. F. Meerassahib, D. G. Mottershead, N. P. Groome, O. Ritvos, and M. P. E. Laitinen. 2005c. Bone morphogenetic protein 15 and growth differentiation factor 9 co-operate to regulate granulosa cell function in ruminants. Reproduction 129:481-487.   DOI
88 McNatty, K. P., J. L. Juengel, T. Wilson, S. M. Galloway, G. H. Davis, N. L. Hudson, C. L. Moeller, M. Cranfield, K. L. Reader, M. P. Laitinen, N. P. Groome, H. R. Sawyer, and O. Ritvos. 2003. Oocyte-derived growth factors and ovulation rate in sheep. Reprod. Suppl. 61:339-351.
89 Mello, R. R. C., J. E. Ferreira, A. P. T. B. Silva, M. R. B. Mello, and H. B. Palhano. 2013. Initial follicular development in cattle. Rev. Bras. Reprod. Anim. 37:328-333.
90 Miyazawa, K., M. Shinozaki, T. Hara, T. Furuya, and K. Miyazono. 2002. Two major Smad pathways in TGF-${\beta}$ superfamily signalling. Genes Cells 7:1191-1204.   DOI
91 Moenter, S. M., R. M. Brand, A. R. Midgley, and F. J. Karsch. 1992. Dynamics of gonadotropin-releasing hormone release during a pulse. Endocrinology 130:503-510.   DOI
92 Moore, R. K., F. Otsuka, and S. Shimasaki. 2003. Molecular basis of bone morphogenetic protein-15 signaling in granulosa cells. J. Biol. Chem. 278:304-310.   DOI
93 Moore, R. K., G. F. Erickson, and S. Shimasaki. 2004. Are BMP-15 and GDF-9 primary determinants of ovulation quota in mammals? Trends Endocrinol. Metab. 15:356-361.
94 Nishimura, R., Y. Kato, D. Chen, S. E. Harris, G. R. Mundy, and T. Yoneda. 1998. Smad5 and DPC4 are key molecules in mediating BMP-2-induced osteoblastic differentiation of the pluripotent mesenchymal precursor cell line C2C12. J. Biol. Chem. 273:1872-1879.   DOI
95 Orisaka, M., K. Tajima, B. K. Tsang, and F. Kotsuji. 2009. Oocyte-granulosa-theca cell interactions during preantral follicular development. J. Ovarian Res. 2:2-9.   DOI
96 Orisaka, M., S. Orisaka, J.-Y. Jiang, J. Craig, Y. Wang, F. Kotsuji, and B. K. Tsang. 2006. Growth differentiation factor 9 is antiapoptotic during follicular development from preantral to early antral stage. Mol. Endocrinol. 20:2456-2468.   DOI
97 Otsuka, F., K. J. McTavish, and S. Shimasaki. 2011. Integral role of GDF-9 and BMP-15 in ovarian function. Mol. Reprod. Dev. 78:9-21.   DOI
98 Otsuka, F., Z. Yao, T. -H. Lee, S. Yamamoto, G. F. Erickson, and S. Shimasaki. 2000. Bone morphogenetic protein-15 identification of target cells and biological functions. J. Biol. Chem. 275:39523-39528.   DOI
99 Pangas, S. A. and M. M. Matzuk. 2005. The art and artifact of GDF9 activity: Cumulus expansion and the cumulus expansion-enabling factor. Biol. Reprod. 73:582-585.   DOI
100 Palmer, J. S., Z. Z. Zhen, C. Hoekstra, N. K. Hayward, P. M. Webb, D. C. Whiteman, N. G. Martin, D. I. Boomsma, D. L. Duffy, and G. W. Montgomery. 2006. Novel variants in growth differentiation factor 9 in mothers of dizygotic twins. J. Clin. Endocrinol. Metab. 91:4713-4716.   DOI
101 Pangas, S. A., C. J. Jorgez, and M. M. Matzuk. 2004. Growth differentiation factor 9 regulates expression of the bone morphogenetic protein antagonist gremlin. J. Biol. Chem. 279:32281-32286.   DOI
102 Paulini, F. 2010. Expression of Growth and Differentiation Factor 9 (GDF9) and Bone Morphogenetic Protein 15(BMP15) and Their Effect on In vitro Luteinization of Bovine Granulosa Cells. Masters Dissertation, School of Agronomy and Veterinary Medicine - UnB, Brasilia, DF, Brazil.
103 Peng, J., Q. Li, K. Wigglesworth, A. Rangarajan, C. Kattamuri, R. T. Peterson, J. J. Eppig, T. B. Thompson, and M. M. Matzuk. 2013. Growth differentiation factor 9:bone morphogenetic protein 15 heterodimers are potent regulators of ovarian functions. Proc. Natl. Acad. Sci. USA. 110:E776-785.   DOI
104 Reader, K. L., D. A. Heath, S. Lun, C. J. McIntosh, A. H. Western, R. P. Littlejohn, K. P. McNatty, and J. L. Juengel. 2011. Signalling pathways involved in the cooperative effects of ovine and murine GDF9+BMP15-stimulated thymidine uptake by rat granulosa cells. Reproduction 142:123-131.   DOI
105 Richard, F. J. and M. A. Sirard. 1996. Effects of follicular cells on oocyte maturation. I: Effects of follicular hemisections on bovine oocyte maturation in vitro. Biol. Reprod. 54:16-21.   DOI
106 Sanchez, F. and J. Smitz. 2012. Molecular control of oogenesis. Biochim. Biophys. Acta. 1822:1896-1912.   DOI
107 Silva, J. R. V., R. Van Den Hurk, M. H. T. Matos, R. R. Santos, C. Pessoa, M. O. Moraes, and J. R. Figueiredo. 2004. Influences of FSH and EGF on primordial follicles during in vitro culture of caprine ovarian cortical tissue. Theriogenology 61:1691-1704.   DOI
108 Shimasaki, S., R. K. Moore, G. F. Erickson, and F. Otsuka. 2003. The role of bone morphogenetic proteins in ovarian function. Reprod. Suppl. 61:323-337.
109 Shimasaki, S., R. K. Moore, F. Otsuka, and G. F. Erickson. 2004. The bone morphogenetic protein system in mammalian reproduction. Endocr. Rev. 25:72-101.   DOI
110 Silva, J. R. V., R. Van Den Hurk, H. T. A. Van Tol, B. A. J. Roelen, and J. R. Figueiredo. 2005. Expression of growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15), and BMP receptors in the ovaries of goats. Mol. Reprod. Dev. 70:11-19.   DOI
111 Silva, J. R. V., C. C. F. Leitao, and I. R. Brito. 2009. Transforming growth factors -${\beta}$ superfamily members and control of folliculogenesis in mammals. Rev. Bras. Reprod. Anim. 33:149-160.
112 Silva, J. R. V., M. A. L. Ferreira, S. H. F. Costa, and J. R. Figuereiredo. 2002. Morphological features and control of follicular growth during folliculogenesis in domestic ruminants. Ciencia Anim. 12:105-117.
113 Spicer, L. J., P. Y. Aad, D. Allen, S. Mazerbourg, and A. J. Hsueh. 2006. Growth differentiation factor-9 has divergent effects on proliferation and steroidogenesis of bovine granulosa cells. J. Endocrinol. 189:329-339.   DOI
114 Su, Y. Q., X. Wu, M. J. O'Brien, F. L. Pendola, J. N. Denegre, M. M. Matzuk, and J. J. Eppig. 2004. Synergistic roles of BMP15 and GDF9 in the development and function of the oocyte-cumulus cell complex in mice: Genetic evidence for an oocyte-granulosa cell regulatory loop. Dev. Biol. 276:64-73.   DOI
115 Tanghe, S., A. Van Soom, H. Nauwynck, M. Coryn, and A. De Kruif. 2002. Minireview: Functions of the cumulus oophorus during oocyte maturation, ovulation, and fertilization. Mol. Mol. Reprod. Dev. 61:414-424.   DOI
116 Su, Y.-Q., K. Sugiura, and J. Eppig. 2009. Mouse oocyte control of granulosa cell development and function: Paracrine regulation of cumulus cell metabolism. Semin. Reprod. Med. 27:32-42.   DOI
117 Su, Y.-Q., K. Sugiura, K. Wigglesworth, M. J. O'Brien, J. P. Affourtit, S. Pangas, M. M. Matzuk, and J. J. Eppig. 2008. Oocyte regulation of metabolic cooperativity between mouse cumulus cells and oocytes: BMP15 and GDF9 control cholesterol biosynthesis in cumulus cells. Development 135:111-121.
118 Sutton, M. L., R. B. Gilchrist, and J. G. Thompson. 2003. Effect of in-vivo and in-vitro environments on the metabolism of the cumulus-oocyte complex and its influence on oocyte developmental capacity. Hum. Reprod. Update 9:35-48.   DOI
119 Vanderhyden, B. C. 1996. Oocyte-secreted factros regulate granulosa cell steroidogenesis. Zygote 4:317-321.   DOI
120 Vanderhyden, B. C. and A. M. Tonary. 1995. Differential regulation of progesterone and estradiol production by mouse cumulus and mural granulosa cells by a factor(s) secreted by the oocyte. Biol. Reprod. 53:1243-1250.   DOI
121 Vanderhyden, B. C., E. A. Macdonald, E. Nagyova, and A. Dhawan. 2003. Evaluation of members of the TGFbeta superfamily as candidates for the oocyte factors that control mouse cumulus expansion and steroidogenesis. Reprod. Suppl. 61:55-70.
122 Vitt, U. A. and A. J. Hsueh. 2001. Stage-dependent role of growth differentiation factor-9 in ovarian follicle development. Mol. Cell Endocrinol. 183:171-177.   DOI