Abstract
This study evaluated the levels of bone morphogenetic protein receptors BMPRIB and BMPRII mRNA in goat follicles and the effects of bone morphogenetic protein-15 (BMP-15) on the in vitro development of cultured preantral follicles. Real-time polymerase chain reaction (PCR) was used to analyze the levels of BMPRIB and BMPRII mRNA in caprine preantral follicles and in small and large antral follicles. Preantral follicles (≥150 μm) were also isolated from goat ovaries and cultured for 18 days in α-MEM+ supplemented with or without BMP-15 (10, 50, or 100 ng/ml). At the end of culture, some follicles were fixed for ultrastructural evaluation. Real-time PCR showed a reduction in BMPRII mRNA levels from the primary to secondary follicles. Higher levels of BMPRIB mRNA were observed in granulosa/theca cells from large antral follicles compared with small antral follicles. Moreover, BMPRII mRNA was expressed to a greater extent in cumulus–oocyte complexes from large antral follicles than in their respective granulosa/theca cells. In culture, 50 ng/ml BMP-15 positively influenced antral cavity formation and follicle growth after 18 days and also maintained follicular integrity. Thus, BMPRIB and BMPRII mRNAs are present in all follicular categories. BMP-15 (50 ng/ml) stimulates growth, antrum formation and the ultrastructural integrity of isolated caprine preantral follicles after 18 days of culture.
Similar content being viewed by others
References
Allendorph GP, Vale WW, Choe S (2006) Structure of the ternary signaling complex of a TGF-β superfamily member. Proc Natl Acad Sci USA 103:7643–7648
Celestino JJH, Lima-Verde IB, Bruno JB, Matos MHT, Chaves RN, Saraiva MVA, Silva CMG, Faustino LR, Rossetto R, Lopes CAP, Donato MAM, Peixoto CA, Campello CC, Silva JRV, Figueiredo JR (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
Chaves RN, Martins FS, Saraiva MVA, Celestino JJH, Lopes CAP, Correia JC, Lima-Verde IB, Matos MHT, Báo SN, Name KPO, Campello CC, Silva JRV, Figueiredo JR (2008) Chilling ovarian fragments during transportation improves viability and growth of goat preantral follicles cultured in vitro. Reprod Fertil Dev 20:640–647
Chen AQ, Yu SD, Wang ZG, Xu ZR, Yang ZG (2009) Stage-specific expression of bone morphogenetic protein type I and type II receptor genes: effects of follicle-stimulating hormone on ovine antral follicles. Anim Reprod Sci 111:391–399
Clelland E, Kohli G, Campbell RK, Sharma S, Shimasaki S, Peng C (2006) Bone morphogenetic protein-15 in the zebrafish ovary: complementary deoxyribonucleic acid cloning, genomic organization, tissue distribution, and role in oocyte maturation. Endocrinology 147:201–209
Clelland ES, Tan Q, Balofsky A, Lacivita R, Peng C (2007) Inhibition of premature oocyte maturation: a role for bone morphogenetic protein 15 in zebrafish ovarian follicles. Endocrinology 148:5451–5458
Crozet N, Dahirel M, Gall L (2000) Meiotic competence of in vitro grown goat oocytes. J Reprod Fertil 118:367–373
Eckery DC, Whale LJ, Lawrence SB, Wylde KA, McNatty KP, Juengel JL (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
Erickson GF, 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 1:9
Galloway SM, McNatty KP, Cambridge LM, Laitinen MP, Juengel JL, Jokiranta TS, McLaren RJ, Luiro K, Dodds KG, Montgomery GW, Beattie AE, Davis GH, Ritvos O (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
Galloway SM, McNatty KP, Cambridge LM, Laitinen MPE, Juengel JL, Jokiranta TS, McLaren RJ, Luiro K, Dodds KG, Montgomery GW, Beattie AE, Davis GH, Ritvos O (2002) 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
Gilboa L, Nohe A, Geissendorfer T, Sebald W, Henis YI, Knaus P (2000) Bone morphogenetic protein receptor complexes on the surface of live cells: a new oligomerization mode for serine/threonine kinase receptors. Mol Biol Cell 11:1023–1035
Gilchrist RB, Lane M, Thompson JG (2008) Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality. Hum Reprod Update 14:159–177
Glister C, Kemp CF, Knight PG (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 127:239–254
Gougeon A (2010) Human ovarian follicular development: from activation of resting follicles to preovulatory maturation. Ann Endocrinol (Paris) 7:132–143
Hanrahan JP, Gregan SM, Mulsant P, Mullen M, Davis GH, Powell R, Galloway SM (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
Hirshfield AN (1991) Development of follicles in mammalian ovary. Int Rev Cytol 124:43–101
Hurk R van den, Spek ER, Hage WJ, Fair T, Ralph JH, Schotanus K (1998) Ultrastructure and viability of isolated bovine preantral follicles. Hum Reprod 4:833–841
Jaatinen R, Laitinen MP, Vuojolainen K, Aaltonen J, Louhio H, Heikinheimo K, Lehtonen E, Ritvos O (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
Jayawardana BC, Shimizu T, Nishimoto H, Kaneko E, Tetsuka M, Miyamoto A (2006) Hormonal regulation of expression of growth differentiation factor-9 receptor type I and II genes in the bovine ovarian follicle. Reproduction 131:545–553
Juengel JL, McNatty KP (2005) The role of proteins of the transforming growth factor-β superfamily in the intraovarian regulation of follicular development. Hum Reprod Update 11:144–161
Juengel JL, Hudson NL, Heath DA, Smith P, Reader KL, Lawrence SB, O’Connell AR, Laitinen MP, Cranfield M, Groome NP, Ritvos O, McNatty KP (2002) Growth differentiation factor-9 and bone morphogenetic protein 15 are essential for ovarian follicular development in sheep. Biol Reprod 67:1777–1789
Juengel JL, Bodensteiner KJ, Heath DA, Hudsona NL, Moeller CL, Smith P, Galloway SM, Davis GH, Sawyer HR, McNatty KP (2004) Physiology of GDF9 and BMP15 signalling molecules. Anim Reprod Sci 82–83:447–460
Laitinen M, Vuojolainen K, Jaatinen R, Ketola I, Aaltonen J, Lehtonen E, Heikinheimo M, Ritvos O (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
Li H, Kuo T, Yang H, Chen L, Li SS, Huang H (2008) 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
Lima IMT, Brito IR, Rodrigues GQ, Silva CMG, Magalhães-Padilha DM, Lima LF, Celestino JJH, Campello CC, Silva JRV, Figueiredo JR, Rodrigues APR (2011) Presence of c-kit mRNA in goat ovaries and improvement of in vitro preantral follicle survival and development with kit ligand. Mol Cell Endocrinol 345:38–47
Lucci CM, Amorim CA, Bao SN, Figueiredo JR, Rodrigues APR, Silva JRV, Gonçalves PBD (1999) Effect of the interval of serial sections of ovarian tissue in the tissue chopper on the number of isolated caprine preantral follicles. Anim Reprod Sci 56:39–49
Lucci CM, Silva JRV, Carvalho FCA, Figueiredo JR, Báo SN (2001) Light microscopical and ultrastrutural characterization of goat preantral follicles. Small Rumin Res 41:61–69
Margulis S, Abir R, Felz C, Nitke S, Krissi H, Fisch B (2009) Bone morphogenetic protein 15 expression in human ovaries from fetuses, girls, and women. Fertil Steril 92:1666–1673
Matos MHT, Silva JRV, Rodrigues APR, Figueiredo JR (2007) Técnicas para avaliação da qualidade de folículos ovarianos pré-antrais cultivados in vitro. Rev Bras Reprod Anim 31:433–442
McNatty KP, Juengel JL, Reader KL, Lun S, Myllymaa S, Lawrence SB, Western A, Meerasahib MF, Mottershead DG, Groome NP, Ritvos O, Laitinen MPE (2005a) Bone morphogenetic protein 15 and growth differentiation factor 9 co-operate to regulate granulosa cell function in ruminants. Reproduction 129:481–487
McNatty KP, Juengel JL, Reader KL, Lun S, Myllymaa S, Lawrence SB, Western A, Meerasahib MF, Mottershead DG, Groome NP, Ritvos O, Laitinen MPE (2005b) Bone morphogenetic protein 15 and growth differentiation factor 9 cooperate to regulate granulosa cell function. Reproduction 129:473–480
Mery L, Lefevre A, Benchaib M, Demirci B, Salle B, Guerin JF, Lornage J (2007) Follicular growth in vitro: detection of growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) during in vitro culture of ovine cortical slices. Mol Reprod Dev 74:767–774
Moore RK, Otsuka F, Shimasaki S (2003) Molecular basis of bone morphogenetic protein-15 signaling in granulosa cells. J Biol Chem 278:304–310
Moore RK, Erickson GF, Shimasaki S (2004) Are BMP-15 and GDF-9 primary determinants of ovulation quota in mammals? Trends Endocrinol Metab 15:356–361
Nohe A, Hassel S, Ehrlich M, Neubauer F, Sebald W, Henis YI, Knaus P (2002) The mode of bone morphogenetic protein (BMP) receptor oligomerization determines different BMP-2 signaling pathways. J Biol Chem 277:5330–5338
Oktem O, Oktay K (2008) The ovary: anatomy and function throughout human life. Ann N Y Acad Sci 112:1–9
Otsuka F (2010) Multiple endocrine regulation by bone morphogenetic protein system. Endocr J 57:3–14
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 99:8060–8065
Otsuka F, Yao Z, Lee T, Yamamoto S, Erickson GF, Shimasaki S (2000) Bone morphogenetic protein-15. Identification of target cells and biological functions. J Biol Chem 275:39523–39528
Otsuka F, Yamamoto S, Erickson GF, Shimasaki S (2001) Bone morphogenetic protein-15 inhibits follicle-stimulating hormone (FSH) action by suppressing FSH receptor expression. J Biol Chem 276:11387–11392
Paradis F, Novak S, Murdoch GK, Dyck MK, Dixon WT, Foxcroft GR (2009) Temporal regulation of BMP2, BMP6, BMP15, GDF9, BMPR1A, BMPR1B, BMPR2 and TGFBR1 mRNA expression in the oocyte, granulosa and theca cells of developing preovulatory follicles in the pig. Reproduction 138:115–129
Paulini F, Melo EO (2011) The role of oocyte-secreted factors GDF9 and BMP15 in follicular development and oogenesis. Reprod Domest Anim 46:354–361
Peng C, Clelland E, Tan Q (2009) Potential role of bone morphogenetic protein-15 in zebrafish follicle development and oocyte maturation. Comp Biochem Physiol 153:83–87
Quinn LR, Shuttleworth G, Hunter MG (2004) Immunohistochemical localization of the bone morphogenetic protein receptors in the porcine ovary. J Anat 205:15–23
Reynaud K, Cortvrindt R, Smitz J, Driancourt MA (2000) Effects of kit ligand and anti-kit antibody on growth of cultured mouse preantral follicles. Mol Reprod Dev 56:483–494
Rodrigues GQ, Silva CMG, Faustino LR, Bruno JB, Magalhães DM, Campello CC, Figueiredo JR (2010) Bovine serum albumin improves in vitro development of caprine preantral follicles. Anim Reprod 7:382–388
SAS Ver. 9.0. (2002) SAS Institute, Cary, N.C., USA
Shimasaki S, Zachow RJ, Li D, Kim H, Iemura S, Ueno N, Sampath K, Chang RJ, Erickson GF (1999) A functional bone morphogenetic protein system in the ovary. Proc Natl Acad Sci USA 96:7282–7287
Shimasaki S, Moore RK, Otsuka F, Erickson GF (2004) The bone morphogenetic protein system in mammalian reproduction. Endocrinol Rev 25:72–101
Silva JR, Hurk R van den, Tol HT van, Roelen BA, Figueiredo JR (2004) Expression of growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP-15), and BMP receptors in the ovaries of goats. Mol Reprod Dev 70:11–19
Silva GM, Araújo VR, Duarte ABG, Chaves RN, Silva CMG, Lobo CH, Almeida AP, Matos MHT, Tavares LMT, Campelo CC, Figueiredo JR (2011) Ascorbic acid improves the survival and in vitro growth of isolated caprine preantral follicles. Anim Reprod 8:14–24
Souza CJ, Campbell BK, McNeilly AS, Baird DT (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 123:363–369
Souza CJH, Melo EO, Moraes JCF, Baird DT (2007) Role of bone morphogenetic proteins in follicle development. In: Gonzalez-Bulnes A (ed) Novel concepts in ovarian endocrinology, vol 1. Transworld Research Network, Kerala, pp 27–42
Sun RZ, Lei L, Cheng L, Jin ZF, Zu SJ, Shan ZY, Wang ZD, Zhang JX, Liu ZH (2010) Expression of GDF-9, BMP-15 and their receptors in mammalian ovary follicles. J Mol Histol 41:325–332
Tol HT van, Bevers MM (1998) Theca cells and theca-cell conditioned medium inhibit the progression of FSH-induced meiosis of bovine oocytes surrounded by cumulus cells connected to membrane granulosa. Mol Reprod Dev 51:315–321
Velilla E, Izquierdo D, Rodriguez-González E, López-Béjar M, Vidal F, Paramio MT (2004) Distribution of prepubertal and adult goat oocyte cortical granules during meiotic maturation and fertilisation: ultrastructural and cytochemical study. Mol Reprod Dev 68:507–514
Wright CS, Hovatta O, Margara R, Trew G, Winston RML, Franks S, Hardy K (1999) Effects of follicle-stimulating hormone and serum substitution on the in-vitro growth of human ovarian follicles. Hum Reprod 14:1555–1562
Wu Y, Tang L, Cai J, Lu X, Xu J, Zhu X, Luo Q, Huang H (2007) High bone morphogenetic protein-15 level in follicular fluid is associated with high quality oocyte and subsequent embryonic development. Hum Reprod 22:1526–1531
Yan C, Wang P, DeMayo J, DeMayo FJ, Elvin JA, Carino C, Prasad SV, Skinner SS, Dunbar BS, Dube JL, Celeste AJ, Matzuk MM (2001) Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Mol Endocrinol 15:854–866
Yoshino O, McMahon HE, 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 103:10678–10683
Acknowledgments
The authors thank Emmanuel Teles Sales for his contribution to the experiments.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was supported by the National Council for Scientific and Technological Development (CNPq, Brazil, grant number: 554812/2006-1- RENORBIO), the Coordination for the Improvement of Higher Education Personnel (CAPES) and the Brazilian Innovation Agency (FINEP). Isadora Machado Teixeira Lima is a recipient of a grant from CAPES.
The authors declare no potential conflict of interests that can be perceived as prejudicing the impartiality of the research reported.
Rights and permissions
About this article
Cite this article
Lima, I.M.T., Brito, I.R., Rossetto, R. et al. 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, 225–238 (2012). https://doi.org/10.1007/s00441-012-1361-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00441-012-1361-4