Hostname: page-component-7f64f4797f-kjzhn Total loading time: 0 Render date: 2025-11-04T14:38:36.372Z Has data issue: false hasContentIssue false
  • English
  • Français

The bone morphogenetic protein system and the regulation of ovarian follicle development in mammals

Published online by Cambridge University Press:  23 January 2015

Rodrigo O.D.S. Rossi ,
José J.N. Costa ,
Anderson W.B. Silva ,
Márcia V.A. Saraiva ,
Robert Van den Hurk  and
José R.V. Silva
Rodrigo O.D.S. Rossi
Affiliation:
Biotechnology Nucleus of Sobral – NUBIS, Federal University of Ceara, Sobral, CE, Brazil.
José J.N. Costa
Affiliation:
Biotechnology Nucleus of Sobral – NUBIS, Federal University of Ceara, Sobral, CE, Brazil.
Anderson W.B. Silva
Affiliation:
Biotechnology Nucleus of Sobral – NUBIS, Federal University of Ceara, Sobral, CE, Brazil.
Márcia V.A. Saraiva
Affiliation:
Biotechnology Nucleus of Sobral – NUBIS, Federal University of Ceara, Sobral, CE, Brazil.
Robert Van den Hurk
Affiliation:
Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, PO Box 80.163, Utrecht, The Netherlands.
José R.V. Silva*
Affiliation:
Biotechnology Nucleus of Sobral – NUBIS, Federal University of Ceara, Av. Comandante Maurocélio Rocha Ponte 100, CEP 62041–040, Sobral, CE, Brazil.
*
All correspondence to: J.R.V. Silva. Biotechnology Nucleus of Sobral – NUBIS, Federal University of Ceara, Av. Comandante Maurocélio Rocha Ponte 100, CEP 62041–040, Sobral, CE, Brazil. Tel:/Fax: +55 88 36118000. e-mail: jrvsilva@ufc.br
Get access Rights & Permissions [Opens in a new window]

Summary

The bone morphogenetic protein (BMP) family consists of several growth factor proteins that belong to the transforming growth factor-β (TGF-β) superfamily. BMPs bind to type I and type II serine–threonine kinase receptors, and transduce signals through the Smad signalling pathway. BMPs have been identified in mammalian ovaries, and functional studies have shown that they are involved in the regulation of oogenesis and folliculogenesis. This review summarizes the role of the BMP system during formation, growth and maturation of ovarian follicles in mammals.

Keywords

Folliculogenesis, OogenesisOvaryTransforming growth factor

Information

Type
Research Article
Information
Zygote , Volume 24 , Issue 1 , February 2016 , pp. 1 - 17
Copyright
Copyright © Cambridge University Press 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Abir, R., Ben-Haroush, A., Melamed, N., Felz, C., Krissi, H. & Fisch, B. (2008). Expression of bone morphogenetic proteins 4 and 7 and their receptors IA, IB, and II in human ovaries from fetuses and adults. Fertil. Steril. 89, 1430–40.CrossRefGoogle Scholar
Akiyama, I., Yoshino, O., Osuga, Y., Shi, J., Hirota, Y., Hirata, T., Harada, M., Koga, K., Fujimoto, A., Yano, T. & Taketani, Y. (2012). The localization and regulation of proprotein convertase subtilisin/kexin (PCSK) 6 in human ovary. Am. J. Reprod. Immunol. 68, 491–8.Google Scholar
Akiyama, I., Yoshino, O., Osuga, Y. Shi, J., Takamura, M., Harada, M., Koga, K., Hirota, Y., Hirata, T., Fujii, T. & Saito, S. (2014). The role of bone morphogenetic protein 6 in accumulation and regulation of neutrophils in the human ovary. Reprod. Sci. 21, 772–7.Google Scholar
Araújo, V.R., Silva, C.M.G., Magalhães, D.M., Silva, G.M., Báo, S.N., Silva, J.R.V., Figueiredo, J.R. & Rodrigues, A.P.R. (2010a). Effect of bone morphogenetic protein-7 (BMP-7) on in vitro survival of caprine preantral follicles. Pesq. Vet. Bras. 30, 305–10.Google Scholar
Araújo, V.R., Lima-Verde, I.B., Name, K.P.O., Bao, S.N., Campello, C.C., Silva, J.R.V., Rodrigues, A.P.R. & Figueiredo, J.R. (2010b). Bone morphogenetic protein-6 (BMP-6) induces atresia in goat primordial follicles cultured in vitro . Pesq. Vet. Bras. 30, 770–6.Google Scholar
Artini, P.G., Monteleone, P., Toldin, M.R.P., Matteucci, C., Ruggiero, M., Cela, V. & Genazzani, A.R. (2007). Growth factors and folliculogenesis in polycystic ovary patients. Expert. Rev. Endocrinol. Metab. 2, 215–7.Google Scholar
Attisano, L., Wrana, J.L., Montalvo, E. & Massagué, J. (1996). Activation of signalling by the activin receptor complex. Mol. Cell Biol. 16, 1066–73.CrossRefGoogle ScholarPubMed
Berkholtz, C.B., Lai, B.E., Woodruff, T.K. & Shea, L.D. (2006). Distribution of extracellular matrix proteins type I collagen, type IV collagen, fibronectin, and laminin in mouse folliculogenesis. Histochem. Cell Biol. 126, 583–92.Google Scholar
Bodin, L., Di Pasquale, E., Fabre, S., Bontoux, M., Monget, P., Persani, L. & Mulsant, P. (2007). A novel mutation in the bone morphogenetic protein 15 gene causing defective protein secretion is associated with both increased ovulation rate and sterility in Lacaune sheep. Endocrinology 148, 393–400.CrossRefGoogle ScholarPubMed
Bragdon, B., Moseychuk, O., Saldanha, S., King, D., Julian, J. & Nohe, A. (2011). Bone morphogenetic proteins: a critical review. Cell Signal. 23, 609–20.Google Scholar
Brankin, V., Quinn, R.L., Webb, R. & Hunter, M.G. (2005) BMP-2 and -6 modulate porcine theca cell function alone and co-cultured with granulosa cells. Domest. Anim. Endocrinol. 29, 593–604.CrossRefGoogle ScholarPubMed
Caixeta, E.S., Sutton McDowall, M.L., Gilchrist, R.B., Thompson, C.A.P., Machado, M.F., Lima, P.F., Buratini, J. (2013). Bone morphogenetic protein 15 and fibroblast growth factor 10 enhance cumulus expansion, glucose uptake, and expression of genes in the ovulatory cascade during in vitro maturation of bovine cumulus–oocyte complexes. Reproduction 146, 27–3.Google Scholar
Canty-Laird, E., Carré, G.A., Mandon-Pépin, B., Kadler, K.E. & Fabre, S. (2010). First evidence of bone morphogenetic protein 1 expression and activity in sheep ovarian follicles. Biol. Reprod. 83, 138–46.Google Scholar
Cao, X.K., Wang, J., Lan, X.Y., Lei, C.Z., Zhang, C.L., Qi, X.L. & Chen, H. (2013). Genetic variants in BMP8B gene are associated with growth traits in Chinese native cattle. Gene 532, 108–13.Google Scholar
Celestino, J.J.H., Lima-Verde, I.B., Bruno, J.B., Matos, M.H.T., Chaves, R.N., Saraiva, M.V.A., Silva, C.M., Faustino, L.R., Rossetto, R., Lopes, C.A., Donato, M.A., Peixoto, C.A., Campello, C.C., Silva, J.R. & Figueiredo, J.R. (2011). Steady state level of bone morphogenetic protein-15 in goat ovaries and its influence on in vitro development and survival of preantral follicles. Mol. Cell Endocrinol. 338, 1–9.Google Scholar
Chang, H., Brown, C.W. & Matzuk, M.M. (2002). Genetic analysis of the mammalian transforming growth factor-beta superfamily. Endocr. Rev. 23, 787–823.Google Scholar
Chang, H.M., Cheng, J.C., Taylor, E. & Leung, P.C. (2014). Oocyte-derived BMP15 but not GDF9 down-regulates connexin 43 expression and decreases gap junction intercellular communication activity in immortalized human granulosa cells. Mol. Hum. Reprod. 20, 373–83.Google Scholar
Chen, Y., Zhao, S., Qiao, J., Liu, P., Lian, Y. & Zheng, X. (2009). Expression of bone morphogenetic protein-15 in human oocyte and cumulus granulosa cells primed with recombinant follicle-stimulating hormone followed by human chorionic gonadotropin. Fertil. Steril. 92, 2045–6.CrossRefGoogle ScholarPubMed
Chhabra, A., Zijerdi, D., Zhang, J., Kline, A., Balian, G. & Hurwitz, S. (2005). BMP-14 deficiency inhibits long bone fracture healing: a biochemical, histologic, and radiographic assessment. J. Orthop. Trauma. 19, 629–34.Google Scholar
Childs, A.J., Kinnell, H.L., Collins, C.S., Hogg, K., Bayne, R.A., Green, S.J., McNeilly, A.S. & Anderson, R.A. (2010). BMP signaling in the human fetal ovary is developmentally regulated and promotes primordial germ cell apoptosis. Stem Cells 28, 1368–78.CrossRefGoogle ScholarPubMed
Constam, D.B. & Robertson, E.J. (2000). SPC4/PACE4 regulates a TGFbeta signaling network during axis formation. Genes Dev. 14, 1146–55.CrossRefGoogle ScholarPubMed
Costa, J.J.N., Passos, M.J., Leitao, C.C.F., Vasconcelos, G.L., Saraiva, M.V.A., Figueiredo, J.R., van den Hurk, R. & Silva, J.R. (2012). Levels of mRNA for bone morphogenetic proteins, their receptors and SMADs in goat ovarian follicles grown in vivo and in vitro. Reprod . Fertil. Dev. 24, 723–32.Google Scholar
Crawford, J.L. & Mcnatty, K.P. (2012). The ratio of growth differentiation factor 9: bone morphogenetic protein 15 mRNA expression is tightly co-regulated and differs between species over a wide range of ovulation rates. Mol. Cell Endocrinol. 348, 339–43.Google Scholar
Dathe, K., Kjaer, K.W., Brehm, A., Meinecke, P., Nürnberg, P., Neto, J.C., Brunoni, D., Tommerup, N., Ott, C.E., Klopocki, E., Seemann, P. & Mundlos, S. (2009). Duplications involving a conserved regulatory element downstream of BMP2 are associated with brachydactyly type A2. Am. J. Hum. Genet. 84, 483–92.Google Scholar
Derynck, R., Gelbart, W.M., Harland, R.M., Heldin, C.H., Kern, S.E., Massagué, J., Melton, D.A., Mlodzik, M., Padgett, R.W., Roberts, A.B., Smith, J., Thomsen, G.H., Vogelstein, B. & Wang, X.F. (1996). Nomenclature: vertebrate mediators of TGF-β family signals. Cell 87, 173.Google Scholar
Ding, X., Zhang, X., Mu, Y., Li, Y. & Hao, J. (2013) Effects of BMP4/SMAD signaling pathway on mouse primordial follicle growth and survival via up-regulation of Sohlh2 and c-kit. Mol. Reprod. Dev. 80, 70–8.CrossRefGoogle ScholarPubMed
Ducy, P. & Karsenty, G. (2000). The family of bone morphogenetic proteins. Kidney Inter. 57, 2207–14.CrossRefGoogle ScholarPubMed
Dudley, B., Palumbo, C., Nalepka, J. & Molyneaux, K. (2010). BMP signaling controls formation of a primordial germ cell niche within the early genital ridges. Dev. Biol. 343, 84–93.Google Scholar
Edwards, S.J., Reader, K.L., Lun, S., Western, A., Lawrence, S., McNatty, K.P. & Juengel, J.L. (2008). The cooperative effect of growth and differentiation factor-9 and bone morphogenetic protein (BMP)-15 on granulosa cell function is modulated primarily through BMP receptor II. Endocrinology 149, 1026–30.Google Scholar
Erickson, G.F. & Shimasaki, S. (2001). The physiology of folliculogenesis: the role of novel growth factors. Fertil. Steril. 76, 943–9.Google Scholar
Erickson, G.F. & Shimasaki, S. (2003) The spatiotemporal expression pattern of the bone morphogenetic protein family in rat ovary cell types during the estrous cycle. Reprod. Biol. Endocrinol. 1, 1–20.Google Scholar
Fatehi, A.N., van den Hurk, R., Colenbrander, B., Daemen, A.J., van Tol, H.T., Monteiro, R.M., Roelen, B.A. & Bevers, M.M. (2005). Expression of bone morphogenetic protein 2 (BMP-2), 4 (BMP-4) and BMP receptors in the bovine ovary but absence of effects of BMP-2 and BMP-4 during IVM on bovine oocyte nuclear maturation and subsequent embryo development. Theriogenology 63, 872–89.Google Scholar
Frank, S., Stark, J., Hardy, K. (2008). Follicle dynamics and anovulation in polycystic ovary syndrome. Hum. Reprod. 14, 367–78.Google Scholar
Frota, I.M., Leitão, C.C., Costa, J.J., van den Hurk, R., Saraiva, M.V.A., Figueiredo, J.R. & Silva, J.R. (2013). Levels of BMP-6 mRNA in goat ovarian follicles and in vitro effects of BMP-6 on secondary follicle development. Zygote 21, 270–8.Google Scholar
Frota, I.M.A., Leitão, C.C.F., Costa, J.J.N., van den Hurk, R., Brito, I.R., Saraiva, M.V.A., Figueiredo, J.R. & Silva, J.R.V. (2011). Effects of BMP-7 and FSH on the development of goat preantral follicles and levels of mRNA for FSH-R, BMP-7 and BMP receptors after in-vitro culture. Anim. Reprod. 8, 25–31.Google Scholar
Galloway, S.M., McNatty, K.P., Cambridge, L.M., Laitinen, M.P., Juengel, J.L., Jokiranta, T.S., McLaren, R.J., Luiro, K., Dodds, K.G., Montgomery, G.W., Beattie, A.E., Davis, G.H. & Ritvos, O. (2000). Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nature Genet. 25, 279–83.Google Scholar
Gilchrist, R.B., Lane, M. & Thompson, J.G. (2008). Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality function and oocyte quality. Hum. Reprod. Update 14, 159–77.Google Scholar
Gitelman, S.E., Kobrin, M.S., Ye, J.Q., Lopez, A.R., Lee, A. & Derynck, R. (1994). Recombinant Vgr-1/BMP-6-expressing tumors induce fibrosis and endochondral bone formation in vivo . J. Cell Biol. 126, 1595–609.Google Scholar
Glister, C., Kemp, C.F. & Knight, P.G. (2004). Bone morphogenetic protein (BMP) ligands and receptors in bovine ovarian follicle cells: actions of BMP-4, -6 and -7 on granulosa cells and differential modulation of Smad-1 phosphorylation by follistatin. Reproduction 127, 239–54.CrossRefGoogle ScholarPubMed
Goto, K., Kamiya, Y., Imamura, T., Miyazono, K. & Miyazawa, K. (2007). Selective inhibitory effects of Smad6 on bone morphogenetic protein type I receptors. J. Biol. Chem. 282, 20603–11.Google Scholar
Hahn, S.A., Schutte, M., Hoque, A.T., Moskaluk, C.A., Costa, L.T., Rozenblum, E., Weinstein, C.L., Fischer, A., Yeo, C.J., Hruban, R.H. & Kern, S.E. (1996). DPC4, a candidate tumor suppressor gene at human chromosome 18. Science 271, 350–3.Google Scholar
Hannan, N.R., Jamshidi, P., Pera, M.F. & Wolvetang, E.J. (2009). BMP-11 and myostatin support undifferentiated growth of human embryonic stem cells in feeder-free cultures. Clon. Stem Cells. 11, 427–35.Google Scholar
Hardy, G. & Kramer, B. (2000). Spatial and temporal localisation of bone morphogenetic protein-3 (osteogenin) in the developing rat submandibular gland. J. S. Afr. Dent. Assoc. 55, 136–41.Google ScholarPubMed
Ho, C.C. & Bernard, D.J. (2009). Bone morphogenetic protein 2 signals via BMPR1A to regulate murine follicle-stimulating hormone beta subunit transcription. Biol. Reprod. 81, 133–41.Google Scholar
Hsieh, M., Zamah, A.M. & Conti, M. (2009). Epidermal growth factor-like growth factors in the follicular fluid: role in oocyte development and maturation. Semin. Reprod. Med. 27, 52–61.Google Scholar
Huet, C., Monget, P., Pisselet, C., Hennequet, C., Locatelli, A. & Monniaux, D. (1998). Chronology of events accompanying follicular atresia in hypophysectomized ewes. Changes in levels of steroidogenic enzymes, connexin 43, insulin-like growth factor II/mannose 6 phosphate receptor, extracellular matrix components, and matrix metalloproteinases. Biol. Reprod. 58, 175–85.Google Scholar
Huet, C., Monget, P., Pisselet, C. & Monniaux, D. (1997). Changes in extracellular matrix components and steroidogenic enzymes during growth and atresia of antral ovarian follicles in the sheep. Biol. Reprod. 56, 1025–34.Google Scholar
Hussein, T.S., Thompson, J.G. & Gilchrist, R.B. (2006). Oocyte-secreted factors enhance oocyte developmental competence. Dev. Biol. 296, 514–21.Google Scholar
Hutt, K.J. & Albertini, D.F. (2007). An oocentric view of folliculogenesis and embryogenesis. Reprod. Biomed. Online 14, 758–64.Google Scholar
Inagaki, K., Otsuka, F., Miyoshi, T., Yamashita, M., Takahashi, M., Goto, J., Suzuki, J. & Makino, H. (2009). p38-Mitogen-activated protein kinase stimulated steroidogenesis in granulosa cell-oocyte cocultures: role of bone morphogenetic proteins 2 and 4. Endocrinology 150, 1921–30.Google Scholar
Israel, D.I., Nove, J., Kerns, K.M., Moutsatsos, I.K. & Kaufman, R.J. (1992). Expression and characterization of bone morphogenetic protein-2 in Chinese hamster ovary cells. Growth Factors 7, 139–50.Google Scholar
Juengel, J.L., Hudson, N.L., Heath, D.A., Smith, P., Reader, K.L., Lawrence, S.B., O’Connell, A.R., Laitinen, M.P., Cranfield, M., Groome, N.P., Ritvos, O. & McNatty, K.P. (2002). Growth differentiation factor 9 and bone morphogenetic protein 15 are essential for ovarian follicular development in sheep. Biol. Reprod. 67, 1777–89.Google Scholar
Juengel, J.L. & McNatty, K.P. (2005). The role of proteins of the transforming growth factor-beta superfamily in the intraovarian regulation of follicular development. Hum. Reprod. Update 11, 143–60.Google Scholar
Juengel, J.L., Reader, K.L., Bibby, A.H., Lun, S., Ross, I., Haydon, L.J. and McNatty, K.P. (2006). The role of bone morphogenetic proteins 2, 4, 6 and 7 during ovarian follicular development in sheep: contrast to rat. Reproduction 131, 501–13.Google Scholar
Kayamori, T., Kosaka, N., Miyamoto, A. & Shimizu, T. (2009). The differential pathways of bone morphogenetic protein (BMP)-4 and -7 in the suppression of the bovine granulosa cell apoptosis. Mol. Cell Biochem. 323, 161–8.CrossRefGoogle ScholarPubMed
Kayani, A.R., Glister, C., Knight, P.G. (2009). Evidence for an inhibitory role of bone morphogenetic protein(s) in the follicular–luteal transition in cattle. Reproduction 137, 67–78.Google Scholar
Kedem, A., Fisch, B., Garor, R., Ben-Zaken, A., Gizunterman, T., Felz, C., Ben-Haroush, A., Kravarusic, D. & Abir, R. (2011). Growth differentiating factor 9 (GDF9) and bone morphogenetic protein 15 both activate development of human primordial follicles in vitro, with seemingly more beneficial effects of GDF9. J. Clin. Endocrinol. Metab. 96, 1246–54.Google Scholar
Khalaf, M., Morera, J., Bourret, A., Reznik, Y., Denoual, C., Herlicoviez, M., Mittre, H. & Benhaim, A. (2013). 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. 168, 437–44.Google Scholar
Kingsley, D.M. (1994). The TGF-β superfamily: new members, new receptors, and new genetic tests of function in different organisms. Genes Dev. 8, 133–46.Google Scholar
Knight, P.G. & Glister, C. (2006). TGF-beta superfamily members and ovarian follicle development. Reproduction 132, 191–206.Google Scholar
Kristensen, S.G., Andersen, K., Clement, C.A., Franks, S., Hardy, K. & Andersen, C.Y. (2014). Expression of TGF-beta superfamily growth factors, their receptors, the associated SMADs and antagonists in five isolated size-matched populations of pre-antral follicles from normal human ovaries. Mol. Hum. Reprod. 20, 293–308.Google Scholar
Lawson, K.A., Dunn, N.R., Roelen, B.A.J., Zeinstra, L.M., Davis, A.M., Wright, C.V.E., Korving, J.P.W.F.M. & Hogan, B.L.M. (1999). BMP4 is required for the generation of primordial germ cells in the mouse embryo. Genes Dev. 13, 424–36.Google Scholar
Lee, W.S., Otsuka, F., Moore, R.K. & Shimasaki, S. (2001). Effect of bone morphogenetic protein-7 on folliculogenesis and ovulation in the rat. Biol. Reprod. 65, 994–9.CrossRefGoogle ScholarPubMed
Lee, M.M., Misra, M., Donahoe, P.K. & MacLaughlin, D.T. (2003). MIS/AMH in the assessment of cryptorchidism and intersex conditions. Mol. Cell Endocrinol. 211, 91–8.Google Scholar
Lee, W.S., Yoon, S.J., Yoon, T.K., Cha, K.Y., Lee, S.K., Shimasaki, S., Lee, S. & Lee, K.A. (2004). Effects of bone morphogenetic protein-7 (BMP-7) on primordial follicular growth in the mouse ovary. Mol. Reprod. Dev. 69, 159–63.Google Scholar
Lee, K.B., Khivansara, V., Santos, M.M., Lamba, P., Yuen, T., Sealfon, S.C. & Bernard, D.J. (2007). Bone morphogenetic protein 2 and activin A synergistically stimulate follicle-stimulating hormone b subunit transcription. J. Mol. Endocrinol. 38, 315–30.Google Scholar
Lembong, J.M.A., Yakoby, N. & Shvartsman, S.Y. (2008). Spatial regulation of BMP signaling by patterned receptor expression. Tissue Eng. Part A 14, 1469–77.Google Scholar
Lima, I.M.T., Brito, I.R., Rossetto, R., Duarte, A.B.G., Rodrigues, G.Q., Saraiva, M.V.A., Costa, J.J., Donato, M.A., Peixoto, C.A., Silva, J.R., Figueiredo, J.R. & Rodrigues, A.P. (2012). BMPRIB and BMPRII mRNA expression levels in goat ovarian follicles and the in vitro effects of BMP-15 on preantral follicle development. Cell Tissue Res. 348, 225–38.Google Scholar
Luckenbach, J.A., Dickey, J.T. & Swanson, P. (2011). Follicle-stimulating hormone regulation of ovarian transcripts for steroidogenesis-related proteins and cell survival, growth and differentiation factors in vitro during early secondary oocyte growth in coho salmon. Gen. Comp. Endocrinol. 171, 52–63.CrossRefGoogle ScholarPubMed
Macias, D., Gañan, Y., Sampath, T.K., Piedra, M.E., Ros, M.A. & Hurle, J.M. (1997). Role of BMP-2 and OP-1 (BMP-7) in programmed cell death and skeletogenesis during chick limb development. Development 124, 1109–17.Google Scholar
Martínez-Glez, V., Valencia, M., Caparrós-Martín, J.A., Aglan, M., Temtamy, S., Tenorio, J., Pulido, V., Lindert, U., Rohrbach, M., Eyre, D., Giunta, C., Lapunzina, P. & Ruiz-Perez, V.L. (2012). Identification of a mutation causing deficient BMP1/mTLD proteolytic activity in autosomal recessive osteogenesis imperfecta. Hum. Mutat. 33, 343–50.Google Scholar
Massagué, J. (1998). TGF-β signal transduction. Annu. Rev. Biochem. 67, 753–91.Google Scholar
Massagué, J. & Wotton, D. (2000). Transcriptional control by the TGF-beta/Smad signaling system. Embo J. 19, 1745–54.Google Scholar
Massagué, J., Seoane, J. & Wotton, D. (2005). Smad transcription factors. Genes Dev. 19, 2783–810.Google Scholar
McIntosh, C.J., Lawrence, S., Smith, P., Juengel, J.L. & McNatty, K.P. (2012). Active immunization against the proregions of GDF9 or BMP15 alters ovulation rate and litter size in mice. Reproduction 143, 195–201.Google Scholar
McNatty, K.P., Smith, P., Moore, L.G., Reader, K., Lun, S., Hanrahan, J.P., Groome, N.P., Laitinen, M., Ritvos, O. & Juengel, J.L. (2005). Oocyte-expressed genes affecting ovulation rate. Mol. Cell Endocrinol. 234, 57–66.Google Scholar
Miyagi, M., Mikawa, S., Sato, T., Hasegawa, T., Kobayashi, S., Matsuyama, Y. & Sato, K. (2012). BMP2, BMP4, noggin, BMPRIA, BMPRIB, and BMPRII are differentially expressed in the adult rat spinal cord. Neuroscience 203, 12–26.Google Scholar
Miyoshi, T., Otsuka, F., Inagaki, K., Otani, H., Takeda, M., Suzuki, J., Goto, J., Ogura, T. & Makino, H. (2007). Differential regulation of steroidogenesis by bone morphogenetic proteins in granulosa cells: involvement of extracellularly regulated kinase signaling and oocyte actions in follicle-stimulating hormone-induced estrogen production. Endocrinology 148, 337–45.Google Scholar
Miyoshi, T., Otsuka, F., Suzuki, J., Takeda, M., Inagaki, K., Kano, Y., Otani, H., Mimura, Y., Ogura, T. & Makino, H. (2006). Mutual regulation of follicle-stimulating hormone signaling and bone morphogenetic protein system in human granulosa cells. Biol. Reprod. 74, 1073–82.Google Scholar
Mulsant, P., Lecerf, F., Fabre, S., Schibler, L., Monget, P., Lanneluc, I., Pisselet, C., Riquet, J., Monniaux, D., Callebaut, I., Cribiu, E., Thimonier, J., Teyssier, J., Bodin, L., Cognié, Y. Chitour, N. & Elsen, J.M. (2001). Mutation in bone morphogenetic protein receptor-IB is associated with increased ovulation rate in Booroola Merino ewes. P. Natl. Acad. Sci. USA 98, 5104–9.CrossRefGoogle ScholarPubMed
Nicol, L., Faure, M.O., McNeilly, J.R., Fontaine, J., Taragnat, C. & McNeilly, A.S. (2008). Bone morphogenetic protein-4 interacts with activin and GnRH to modulate gonadotrophin secretion in LbT2 gonadotrophs. J. Endocrinol. 196, 497–507.Google Scholar
Nikaido, M., Tada, M., Saji, T. and Ueno, N. (1997). Conservation of BMP signaling in zebrafish mesoderm patterning. Mech. Dev. 61, 75–88.Google Scholar
Nilsson, E.E. & Skinner, M.K. (2003). Bone morphogenetic protein-4 acts as an ovarian follicle survival factor and promotes primordial follicle development. Biol. Reprod. 69, 1265–72.Google Scholar
Ohta, Y., Nakagawa, K., Imai, Y., Katagiri, T., Koike, T. & Takaoka, K. (2008). Cyclic AMP enhances Smad-mediated BMP signaling through PKA-CREB pathway. J. Bone Miner. Metab. 26, 478–84.Google Scholar
Otsuka, F, Moore, KR & Shimasaki, S. (2001). Biological function and cellular mechanisms of bone morphogenetic protein-6 in the ovary. J. Biol. Chem. 276, 32889–95.Google Scholar
Otsuka, F. & Shimasaki, S. (2002). A negative feedback system between oocyte bone morphogenetic protein 15 and granulosa cell kit ligand: its role in regulating granulosa cell mitosis. Proc. Natl. Acad. Sci. USA 99, 8060–5.Google Scholar
Otsuka, F., McTavish, K. & Shimasaki, S. (2011). Integral role of GDF-9 and BMP-15 in ovarian function. Mol. Reprod. Dev. 78, 9–21.Google Scholar
Otsuka, F., Yao, Z., Lee, T., Yamamoto, S., Erickson, G.F. & Shimasaki, S. (2000). Bone morphogenetic protein-15. Identification of target cells and biological functions. J. Biol. Chem. 275, 39523–8.CrossRefGoogle ScholarPubMed
Padhy, N., Sathya, M.L. & Varma, T.R. (2009). Antral follicle size in the downregulated cycle and is relation to in vitro fertilization outcome. J. Hum. Reprod. Sci. 2, 68–71.CrossRefGoogle ScholarPubMed
Park, S.S., Park, M.J., Joo, B.S., Joo, J.K., Son, J.B. & Lee, K.S. (2012). Improvement of ovarian response and oocyte quality of aged female by administration of bone morphogenetic protein-6 in a mouse model. Reprod. Biol. Endocrinol. 10, 117.Google Scholar
Passos, M.J., Vasconcelos, G.L., Silva, A.W., Brito, I.R., Saraiva, M.V., Magalhães, D.M., Costa, J.J., Donato, M.A., Ribeiro, R.P., Cunha, E.V., Peixoto, C.A., Campello, C.C., Figueiredo, J.R., van den Hurk, R. & Silva, J.R. (2013). Accelerated growth of bovine preantral follicles in vitro after stimulation with both FSH and BMP-15 is accompanied by ultrastructural changes and increased atresia. Theriogenology 79, 1269–77.Google Scholar
Peng, J., Li, Q., Wigglesworth, K., Rangarajan, A., Kattamuri, C., Peterson, R.T., Eppig, J.J., Thompson, T.B. & Matzuk, M.M. (2013). Growth differentiation factor 9: bone morphogenetic protein 15 heterodimers are potent regulators of ovarian functions. Proc. Natl. Acad. Sci. USA 110, 776–85.Google Scholar
Pierre, A., Pisselet, C., Dupont, J., Bontoux, M. & Monget, P. (2005). Bone morphogenetic protein 5 expression in the rat ovary: biological effects on granulosa cell proliferation and steroidogenesis. Biol. Reprod. 73, 1102–8.Google Scholar
Qiao, J. & Feng, H.L. (2011). Extra- and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence. Hum. Reprod. Update 17, 17–33.Google Scholar
Ross, A.J., Tilman, C., Yao, H., MacLaughlin, D. & Capel, B. (2003). AMH induces mesonephric cell migration in XX gonads. Mol. Cell Endocrinol. 211, 1–7.Google Scholar
Saitou, M. & Yamaji, M. (2010). Germ cell specification in mice: Signaling, transcription regulation, and epigenetic consequences. Reproduction 139, 931–42.CrossRefGoogle ScholarPubMed
Samad, T.A., Rebbapragada, A., Bell, E., Zhang, Y., Sidis, Y., Jeong, S.J., Campagna, J.A., Perusini, S., Fabrizio, D.A., Schneyer, A.L., Lin, H.Y., Brivanlou, A.H., Attisano, L. & Woolf, C.J. (2005). DRAGON, a bone morphogenetic protein co-receptor. J. Biol. Chem. 280, 14122–9.Google Scholar
Sánchez, F., Adriaenssens, T., Romero, S. & Smitz, J. (2009). Quantification of oocyte-specific transcripts in follicle-enclosed oocytes during antral development and maturation in vitro . Mol. Hum. Reprod. 15, 539–50.Google Scholar
Savage, C., Das, P., Finelli, A.L., Townsend, S.R., Sun, C.Y., Baird, S.E. & Padgett, R.W. (1996). Caenorhabditis elegans genes sma-2, sma-3, and sma-4 define a conserved family of transforming growth factor-β pathway components. Proc. Natl. Acad. Sci. USA 93, 790–4.Google Scholar
Seidah, N.G. & Chretien, M. (1999). Proprotein and prohormone convertases: a family of subtilases generating diverse bioactive polypeptides. Brain Res. 848, 45–62.Google Scholar
Selvaraju, S., Folger, J.K., Gupta, P.S., Ireland, J.J., Smith, G.W. (2013). Stage-specific expression and effect of bone morphogenetic protein 2 on bovine granulosa cell estradiol production: regulation by cocaine and amphetamine regulated transcript. Domest. Anim. Endocrinol. 44, 115–20.Google Scholar
Sekelsky, J.J., Newfeld, S.J., Raftery, L.A., Chartoff, E.H. & Gelbart, W.M. (1995). Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster . Genetics 139, 1347–58.Google Scholar
Shi, J., Yoshino, O., Osuga, Y., Akiyama, I., Harada, M., Koga, K., Fujimoto, A., Yano, T. & Taketani, Y. (2012). Growth differentiation factor 3 is induced by bone morphogenetic protein 6 (BMP-6) and BMP-7 and increases luteinizing hormone receptor messenger RNA expression in human granulosa cells. Fertil. Steril. 97, 979–83.Google Scholar
Shi, J., Yoshino, O., Osuga, Y., Nishii, O., Yano, T. & Taketani, Y. (2010). Bone morphogenetic protein 7 (BMP-7) increases the expression of follicle-stimulating hormone (FSH) receptor in human granulosa cells. Fertil. Steril. 93, 1273–9.Google Scholar
Shimasaki, S., Zachow, R.J., Li, D., Kim, H., Iemura, S., Ueno, N., Sampath, K., Chang, R.J., Erickson, G.F. (1999). A functional bone morphogenetic protein system in the ovary. Proc. Natl. Acad. Sci. USA 96, 7282–7.Google Scholar
Shimasaki, S., Moore, R.K., Otsuka, F., Erickson, G.F. (2004). The bone morphogenetic protein system in mammalian reproduction. Endocr. Rev. 25, 72–101.Google Scholar
Shimizu, T., Yokoo, M., Miyake, Y., Sasada, H., Sato, E. (2004). Differential expression of bone morphogenetic protein 4–6 (BMP-4, -5, and -6) and growth differentiation factor-9 (GDF-9) during ovarian development in neonatal pigs. Domest. Anim. Endocrinol. 27, 397–405.Google Scholar
Silva, J.R.V., van den Hurk, R., van Tol, H.T., Roelen, B.A. & Figueiredo, J.R. (2006). The Kit ligand/c-Kit receptor system in goat ovaries: gene expression and protein localization. Zygote 14, 317–28.Google Scholar
Silva, J.R.V., van den Hurk, R., van Tol, H.T.A., Roelen, B.A.J. & Figueiredo, J.R. (2005). Expression of growth differentiation factor-9 (GDF-9), bone morphogenetic protein 15 (BMP-15) and BMP receptors in the ovaries of goats. Mol. Reprod. Dev. 70, 11–9.CrossRefGoogle ScholarPubMed
Song, K., Krause, C., Shi, S., Patterson, M., Suto, R., Grgurevic, L., Vukicevic, S., van Dinther, M., Falb, D., Ten Dijke, P. & Alaoui-Ismaili, M.H. (2010). Identification of a key residue mediating bone morphogenetic protein (BMP)-6 resistance to noggin inhibition allows for engineered BMPs with superior agonist activity. J. Biol. Chem. 285, 12169–80.Google Scholar
Souza, C.J., Campbell, B.K., McNeilly, A.S. & Baird, D.T. (2002) Effect of bone morphogenetic protein 2 (BMP2) on oestradiol and inhibin A production by sheep granulosa cells, and localization of BMP receptors in the ovary by immunohistochemistry. Reproduction 123, 363–9.Google Scholar
Sugimura, S., Ritter, L.J., Sutton-McDowall, M.L., Mottershead, D.G., Thompson, J.G. & Gilchrist, R.B. (2014). Amphiregulin co-operates with bone morphogenetic protein 15 to increase bovine oocyte developmental competence: effects on gap junction-mediated metabolite supply. Mol. Hum. Reprod. 20, 499–513.Google Scholar
Sugiyama, R., Fuzitou, A., Takahashi, C., Akutagawa, O., Ito, H., Nakagawa, K., Sugiyama, R., Isaka, K. (2010). Bone morphogenetic protein 2 may be a good predictor of success in oocyte fertilization during assisted reproductive technology. Hum. Cell 23, 83–8.Google Scholar
Takebayashi, K., Takakura, K., Wang, H., Kimura, F., Kasahara, K., Noda, Y. (2000). Mutation analysis of the growth differentiation factor-9 and -9B genes in patients with premature ovarian failure and polycystic ovary syndrome. Fertil. Steril. 74: 976–9.Google Scholar
Tandon, M., Gokul, K., Ali, S.A., Chen, Z., Lian, J., Stein, G.S. & Pratap, J. (2012). Runx2 mediates epigenetic silencing of the bone morphogenetic protein-3B (BMP-3B/GDF10) in lung cancer cells. Mol. Cancer. 18, 11–27.Google Scholar
Tanno, T., Noel, P. & Miller, J.L. (2010). Growth differentiation factor 15 in erythroid health and disease. Curr. Opin. Hematol. 17, 184–90.Google Scholar
Teixeira Filho, F.L., Baracat, E.C., Lee, T.H., Suh, C.S., Matsui, M., Chang, R.J., Shimasaki, S. & Erickson, G.F. (2002). Aberrant expression of growth differentiation factor-9 in oocytes of women with polycystic ovary syndrome. J Clin. Endocrinol. Metab. 87, 1337–44.Google Scholar
Urist, M.R. (1965). Bone: formation by autoinduction. Science 150, 893–9.Google Scholar
Vitt, U.A., Hsu, S.Y. & Hsueh, A.J.W. (2001). Evolution and classification of cystine knot-containing hormones and related extracellular signaling molecules. Mol. Endocrinol. 15, 681–94.Google Scholar
Wang, E.A., Rosen, V., D’Alessandro, J.S., Bauduy, M., Cordes, P., Harada, T., Israel, D., Hewick, R.M., Kerns, K.M., Lapan, P., Luxenberg, D.P., McQuaid, D., Moutsatsos, I.K., Nove, J., Wozney, J.M. (1990). Recombinant human bone morphogenetic protein induces bone formation. Proc. Natl. Acad. Sci. USA 87, 2220–4.CrossRefGoogle ScholarPubMed
West, F.D., Roche-Rios, M.I., Abraham, S., Rao, R.R., Natrajan, M.S., Bacanamwo, M. & Stice, S.L. (2010). KIT ligand and bone morphogenetic protein signaling enhances human embryonic stem cell to germ-like cell differentiation. Hum. Reprod. 25, 168–78.Google Scholar
Wieser, R., Wrana, J.L. & Massagué, J. (1995). GS domain mutations that constitutively activate TβR-I, the downstream signaling component in the TGF-β receptor complex. EMBO J. 14, 2199–208.Google Scholar
Williams, L.A., Bhargav, D. & Diwan, A.D. (2008). Unveiling the Bmp13 enigma: redundant morphogen or crucial regulator? Int. J. Biol. Sci. 4, 318–29.Google Scholar
Wilson, T., Wu, X.Y., Juengel, J.L., Ross, I.K., Lumsden, J.M. & Lord, E.A. (2001). Highly prolific Booroola sheep have a mutation in the intracellular kinase domain of bone morphogenetic protein IB receptor (ALK-6) that is expressed in both oocytes and granulosa cells. Biol. Reprod. 64, 1225–35.Google Scholar
Witthuhn, B.A. & Bernlohr, D.A. (2001) Upregulation of bone morphogenetic protein GDF-3/Vgr-2 expression in adipose tissue of FABP4/aP2 null mice. Cytokine 14, 129–35.Google Scholar
Wrana, J.L., Attisano, L., Wieser, R., Ventura, F. & Massagué, J. (1994). Mechanism of activation of the TGF-β receptor. Nature 370, 341–7.Google Scholar
Wu, Y.T., Tang, L., Cai, J., Lu, X.E., Xu, J., Zhu, X.M., Luo, Q. & Huang, H.F. (2007). High bone morphogenetic protein-15 level in follicular fluid is associated with high quality oocyte and subsequent embryonic development. Hum. Reprod. 22, 1526–31.Google Scholar
Wu, Y.T., Wang, T.T., Chen, X.J., Zhu, X.M., Dong, M.Y., Sheng, J.Z., Xu, C.M. & Huang, H.F. (2012). Bone morphogenetic protein-15 in follicle fluid combined with age may differentiate between successful and unsuccessful poor ovarian responders. Reprod. Biol. Endocrinol. 10, 1–6.Google Scholar
Xia, Y., Yu, P.B., Sidis, Y., Beppu, H., Bloch, K.D., Schneyer, A.L. & Lin, H.Y. (2007). Repulsive guidance molecule RGMa alters utilization of bone morphogenetic protein (BMP) type II receptors by BMP2 and BMP4. J. Biol. Chem. 282, 18129–40.Google Scholar
Yeh, L.C. & Lee, J.C. (2010). Effects of cartilage-derived morphogenetic protein-3 on the expression of chondrogenic and osteoblastic markers in the pluripotent mesenchymal C3H10T1/2 cell line. Growth Factors 28, 117–28.Google Scholar
Ying, Y. & Zhao, G.Q. (2001). Cooperation of endoderm-derived BMP2 and extraembryonic ectoderm-derived BMP4 in primordial germ cell generation in the mouse. Dev. Biol. 232, 484–92.Google Scholar
Ying, Y., Liu, X.M., Marble, A., Lawson, K.A. & Zhao, G.Q. (2000). Requirement of BMP8b for the generation of primordial germ cells in the mouse. Mol. Endocrinol. 14, 1053–63.Google Scholar
Yoshimura, Y. & Wallach, E.E. (1987). Studies of the mechanism(s) of mammalian ovulation. Fert. Steril. 47, 22–34.Google Scholar
Yoshino, O., McMahon, H.E., Sharma, S. & Shimasaki, S. (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, 10678–83.Google Scholar
Zhao, G.Q. & Hogan, B.L. (1996). Evidence that mouse Bmp8a (Op2) and Bmp8b are duplicated genes that play a role in spermatogenesis and placental development. Mech. Dev. 57, 159–68.Google Scholar