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Role of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Ovarian Function and Their Importance in Mammalian Female Fertility - A Review
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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; Cruz, Maria Helena Coelho; Leal, Claudia Lima Verde;
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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-) 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.
Cumulus Cells;Granulosa Cells;Oocyte Maturation;Follicular Development;Reproductive Efficiency;TGF- Superfamily;
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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.

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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.

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. crossref(new window)

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. crossref(new window)

Buratini Jr, J. 2007. Endocrine and local control of folliculogenesis in cattle. Rev. Bras. Reproducao Anim. 31:190-196.

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.

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.

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

Derynck, R. 1998. Developmental biology: SMAD proteins and mammalian anatomy. Nature 393:737-739. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

Edson, M. A., A. K. Nagaraja, and M. M. Matzuk. 2009. The mammalian ovary from genesis to revelation. Endocr. Rev. 30:624-712. crossref(new window)

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. crossref(new window)

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. crossref(new window)

Eppig, J. J. 2001. Oocyte control of ovarian follicular development and function in mammals. Reproduction 122:829-838. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

Fair, T. 2003. Follicular oocyte growth and acquisition of developmental competence. Anim. Reprod. Sci. 78:203-216. crossref(new window)

Fair, T. 2013. Molecular and endocrine determinants of oocyte competence. Anim. Reprod. 10:277-282.

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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.

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

Hennet, M. L. and C. M. H. Combelles. 2012. The antral follicle: A microenvironment for oocyte differentiation. Int. J. Dev. Biol. 56:819-831. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

Hussein, T. S., J. G. Thompson, and R. B. Gilchrist. 2006. Oocyte-secreted factors enhance oocyte developmental competence. Dev. Biol. 296:514-521. crossref(new window)

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. crossref(new window)

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. crossref(new window)

Hutt, K. J. and D. F. Albertini. 2007. An oocentric view of folliculogenesis and embryogenesis. Reprod. Biomed. Online 14:758-764. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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.

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.

Matzuk, M. M. and K. H. Burns. 2012. Genetics of mammalian reproduction: Modeling the end of the germline. Annu. Rev. Physiol. 74:503-528. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

McGrath, S. A., A. F. Esquela, and S. J. Lee. 1995. Oocyte-specific expression of growth/differentiation factor-9. Mol. Endocrinol. 9:131-136.

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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.

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.

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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.

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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.

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

Sanchez, F. and J. Smitz. 2012. Molecular control of oogenesis. Biochim. Biophys. Acta. 1822:1896-1912. crossref(new window)

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.

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)