The local regulation of folliculogenesis by members of the transforming growth factor superfamily and its relevance for advanced breeding programmes
Regulation of the growth and maturation of the ovarian follicle is critical for normal reproductive function. Alterations in this growth can lead to pathological conditions, such as cystic follicles, reduced oocyte quality, or an abnormal endocrine environment leading to poor fertility. Alterations in follicular growth also influence the number of follicles ovulating and thus can change litter size. Both endocrine factors, such as follicle stimulating hormone and luteinizing hormone, as well as local factors, are known to regulate follicular growth and development. This review will focus on the role of local factors in regulation of ovarian follicular growth in ruminants, with a focus on members of the transforming growth factor superfamily. The potential role of these factors in regulating proliferation, apoptosis, steroidogenesis and responsiveness to gonadotrophins will be considered.
An X, Song Y, Hou J, Zhang Y, Chen K, Ma H, Zhao X, Li G, Gao K, Wang S, Cao B, Bai Y. 2017. ChimiR-4110 promotes granulosa cell apoptosis by targeting Sma- and Mad-related protein 2 (Smad2) in the caprine ovary. PLoS One, 12:e0181162. doi: 10.1371/journal.pone.0181162.
Bao B, Garverick HA. 1998. Expression of steroidogenic enzyme and gonadotropin receptor genes in bovine follicles during ovarian follicular waves: a review. J Anim Sci, 76:1903-1921.
Barros VR, Cavalcante AY, Macedo TJ, Barberino RS, Lins TL, Gouveia BB, Menezes VG, Queiroz MA, Araujo VR, Palheta RC, Jr, Leite MC, Matos MH. 2013. Immunolocalization of melatonin and follicle-stimulating hormone receptors in caprine ovaries and their effects during in vitro development of isolated pre-antral follicles. Reprod Domest Anim, 48:1025-1033.
Batista AM, Silva DM, Rego MJ, Silva FL, Silva EC, Beltrao EI, Gomes Filho MA, Wischral A, Guerra MM. 2013. The expression and localization of leptin and its receptor in goat ovarian follicles. Anim Reprod Sci, 141:142-147.
Bezard J, Vigier B, Tran D, Mauleon P, Josso N. 1987. Immunocytochemical study of anti-Mullerian hormone in sheep ovarian follicles during fetal and postnatal development. J Reprod Fertil, 80:509-516.
Braw-Tal R, McNatty KP, Smith P, Heath DA, Hudson NL, Phillips DJ, McLeod BJ, Davis GH. 1993. Ovaries of ewes homozygous for the X-linked Inverdale gene (FecXI) are devoid of secondary and tertiary follicles but contain many abnormal structures. Biol Reprod, 49:895-907.
Braw-Tal R. 1994. Expression of mRNA for follistatin and inhibin/activin subunits during follicular growth and atresia. J Mol Endocrinol, 13:253-264.
Brito IR, Lima IM, Saraiva MV, Silva CM, Magalhaes-Padilha DM, Araujo VR, Barreto Luz V, Barbalho Silva AW, Campello CC, Silva JR, Figueiredo JR. 2012. Expression levels of mRNAencoding PDGF receptors in goat ovaries and the influence of PDGF on the in vitro development of caprine pre-antral follicles. Reprod Domest Anim, 47:695-703.
Buratini J Jr, Pinto MG, Castilho AC, Amorim RL, Giometti IC, Portela VM, Nicola ES, Price CA. 2007. Expression and function of fibroblast growth factor 10 and its receptor, fibroblast growth factor receptor 2B, in bovine follicles. Biol Reprod, 77:743-750.
Buratini J, Price CA. 2011. Follicular somatic cell factors and follicle development. Reprod Fertil Dev, 23:32-39.
Campbell BK, Souza CJ, Skinner AJ, Webb R, Baird DT. 2006. Enhanced response of granulosa and theca cells from sheep carriers of the FecB mutation in vitro to gonadotropins and bone morphogenic protein-2, -4, and -6. Endocrinology, 147:1608-1620.
Campbell BK, Hernandez-Medrano J, McNeilly AS, Webb R, Picton HM. 2014. Ovarian function in domestic ruminants: mechanistic and translational aspects. In: Juengel JL, Miyamoto A, Price C, Reynolds LP, Smith MF, Webb R (Ed.). Reproduction in Domestic Ruminants VIII: Proceedings of the Ninth International Symposium on Reproduction in Domestic Ruminants, 2014, Obihiro, Hokkaido, Japan. Ashby-dela-Zouch, UK: Context Products Ltd. pp. 359-373.
Chen H, Liu C, Jiang H, Gao Y, Xu M, Wang J, Liu S, Fu Y, Sun X, Xu J, Zhang J, Dai L. 2017. Regulatory role of miRNA-375 in expression of BMP15/GDF9 receptors and its effect on proliferation and apoptosis of bovine cumulus cells. Cell Physiol Biochem, 41:439-450.
Costa JJ, Passos MJ, Leitao CC, Vasconcelos GL, Saraiva MV, Figueiredo JR, van den Hurk R, Silva JR. 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, 24:723-732.
Crawford JL, Heath DA, Reader KL, Quirke LD, Hudson NL, Juengel JL, McNatty KP. 2011. Oocytes in sheep homozygous for a mutation in bone morphogenetic protein receptor 1B express lower mRNA levels of bone morphogenetic protein 15 but not growth differentiation factor 9. Reproduction, 142:53- 61.
Davis GH, McEwan JC, Fennessy PF, Dodds KG, McNatty KP, O WS. 1992. Infertility due to bilateral ovarian hypoplasia in sheep homozygous (FecXI FecXI) for the Inverdale prolificacy gene located on the X chromosome. Biol Reprod, 46:636-640.
Diaz PU, Hein GJ, Belotti EM, Rodriguez FM, Rey F, Amweg AN, Matiller V, Baravalle ME, Ortega HH, Salvetti NR. 2016. BMP2, 4 and 6 and BMPR1B are altered from early stages of bovine cystic ovarian disease development. Reproduction, 152:333-350.
Driancourt MA, Cahill LP, Bindon BM. 1985. Ovarian follicular populations and preovulatory enlargement in Booroola and control Merino ewes. J Reprod Fertil, 73:93-107.
Edwards SJ, Reader KL, Lun S, Western A, Lawrence S, McNatty KP, Juengel JL. 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, 149:1026-1030.
Estienne A, Price CA. 2018. The fibroblast growth factor 8 family in the female reproductive tract. Reproduction, 155:R53-R62.
Fabre S, Pierre A, Pisselet C, Mulsant P, Lecerf F, Pohl J, Monget P, Monniaux D. 2003. The Booroola mutation in sheep is associated with an alteration of the bone morphogenetic protein receptor-IB functionality. J Endocrinol, 177:435-444.
Feary ES, Juengel JL, Smith P, French MC, O'Connell AR, Lawrence SB, Galloway SM, Davis GH, McNatty KP. 2007. Patterns of expression of messenger RNAs encoding GDF9, BMP15, TGFBR1, BMPR1B, and BMPR2 during follicular development and characterization of ovarian follicular populations in ewes carrying the Woodlands FecX2W mutation. Biol Reprod, 77:990-998.
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 dosagesensitive manner. Nat Genet, 25:279-283.
Garcia-Guerra A, Canavessi AMO, Monteiro PLJ, Jr., Mezera MA, Sartori R, Kirkpatrick BW, Wiltbank MC. 2018a. Trio, a novel bovine high fecundity allele: III. Acquisition of dominance and ovulatory capacity at a smaller follicle size. Biol Reprod, 98:350-365.
Garcia-Guerra A, Kamalludin MH, Kirkpatrick BW, Wiltbank MC. 2018b. Trio a novel bovine highfecundity allele: II. Hormonal profile and follicular dynamics underlying the high ovulation rate. Biol Reprod, 98:335-349.
Gilchrist RB, Morrissey MP, Ritter LJ, Armstrong DT. 2003. Comparison of oocyte factors and transforming growth factor-beta in the regulation of DNA synthesis in bovine granulosa cells. Mol Cell Endocrinol, 201:87-95.
Gilchrist RB, Ritter LJ, Myllymaa S, Kaivo-Oja N, Dragovic RA, Hickey TE, Ritvos O, Mottershead DG. 2006. Molecular basis of oocyte-paracrine signalling that promotes granulosa cell proliferation. J Cell Sci, 119:3811-3821.
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.
Glister C, Richards SL, Knight PG. 2005. Bone morphogenetic proteins (BMP) -4, -6, and -7 potently suppress basal and luteinizing hormone-induced androgen production by bovine theca interna cells in primary culture: could ovarian hyperandrogenic dysfunction be caused by a defect in thecal BMP signaling? Endocrinology, 146:1883-1892.
Glister C, Satchell L, Knight PG. 2010. Changes in expression of bone morphogenetic proteins (BMPs), their receptors and inhibin co-receptor betaglycan during bovine antral follicle development: inhibin can antagonize the suppressive effect of BMPs on thecal androgen production. Reproduction, 140:699-712.
Hao L, Wang D, Zhang G, Ma W, Li C, Jiang H. 2014. Vascular endothelial growth factor expression correlated with microvessel density in the antral follicle of sheep. Livest Sci, 165:212.
Hussein TS, Froiland DA, Amato F, Thompson JG, Gilchrist RB. 2005. Oocytes prevent cumulus cell apoptosis by maintaining a morphogenic paracrine gradient of bone morphogenetic proteins. J Cell Sci, 118:5257-5268.
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, Bibby AH, Reader KL, Lun S, Quirke LD, Haydon LJ, McNatty KP. 2004a. The role of transforming growth factor-beta (TGF-beta) during ovarian follicular development in sheep. Reprod Biol Endocrinol, 2:78. doi: 10.1186/1477-7827-2-78
Juengel JL, Hudson NL, Whiting L, McNatty KP. 2004b. Effects of immunization against bone morphogenetic protein 15 and growth differentiation factor 9 on ovulation rate, fertilization, and pregnancy in ewes. Biol Reprod, 70:557-561.
Juengel JL, Heath DA, Quirke LD, McNatty KP. 2006a. Oestrogen receptor alpha and beta, androgen receptor and progesterone receptor mRNA and protein localisation within the developing ovary and in small growing follicles of sheep. Reproduction, 131:81-92.
Juengel JL, Reader KL, Bibby AH, Lun S, Ross I, Haydon LJ, McNatty KP. 2006b. The role of bone morphogenetic proteins 2, 4, 6 and 7 during ovarian follicular development in sheep: contrast to rat. Reproduction, 131:501-513.
Juengel JL, Hudson NL, Berg M, Hamel K, Smith P, Lawrence SB, Whiting L, McNatty KP. 2009. Effects of active immunization against growth differentiation factor 9 and/or bone morphogenetic protein 15 on ovarian function in cattle. Reproduction, 138:107-114.
Juengel JL, Quirke LD, Lun S, Heath DA, Johnstone PD, McNatty KP. 2011. Effects of immunizing ewes against bone morphogenetic protein 15 on their responses to exogenous gonadotrophins to induce multiple ovulations. Reproduction, 142:565-572.
Juengel JL, Davis GH, McNatty KP. 2013a. Using sheep lines with mutations in single genes to better understand ovarian function. Reproduction, 146:R111- 123.
Juengel JL, Proctor LE, Wearne K, Olliver D, Hudson NL, Jensen D, Davis GH, Johnstone PD, McNatty KP. 2013b. Effects of immunization against androstenedione or bone morphogenetic protein 15 (BMP15) on reproductive performance in sheep. J Anim Sci, 91:5946-5953.
Juengel JL, Smith P. 2014. Formation of ovarian foliclles in ruminants. In: Juengel JL, Miyamoto A, Price CA, Reynolds LP, Smith MF, Webb R (Ed.). Reproduction in domestic ruminants VIII: Proceedings of the Ninth International Symposium on Reproduction in Domestic Ruminants, Obihiro, 2014, Hokkaido, Japan. Ashby-de-la-Zouch, UK: Context Products Ltd. pp. 277-293.
Juengel JL, French MC, Quirke LD, Kauff A, Smith GW, Johnstone PD. 2017. Differential expression of CART in ewes with differing ovulation rates. Reproduction, 153:471-479.
Juengel JL. 2018. How the quest to improve sheep reproduction provided insight into oocyte control of follicular development. J R Soc N Z, 48:143-163.
Kamalludin MH, Garcia-Guerra A, Wiltbank MC, Kirkpatrick BW. 2018. Trio, a novel high fecundity allele: I. Transcriptome analysis of granulosa cells from carriers and noncarriers of a major gene for bovine ovulation rate. Biol Reprod, 98:323-334.
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- 168.
Knight PG, Satchell L, Glister C. 2012. Intra-ovarian roles of activins and inhibins. Mol Cell Endocrinol, 359:53-65.
Knight PG, Glister C. 2014. Theca cells and the regulation of ovarian androgen production. In: Juengel JL, Miyamoto A, Price C, Reynolds LP, Smith MF, Webb R (Ed.). Reproduction in Domestic Ruminants VIII: Proceedings of the Ninth International Symposium on Reproduction in Domestic Ruminants, Obihiro, 2014, Hokkaido, Japan. Ashby-de-la-Zouch, UK: Context Products Ltd. pp. 295-310.
Kobayashi Y, Jimenez-Krassel F, Li Q, Yao J, Huang R, Ireland JJ, Coussens PM, Smith GW. 2004. Evidence that cocaine- and amphetamineregulated transcript is a novel intraovarian regulator of follicular atresia. Endocrinology, 145:5373-5383.
Leeuwenberg BR, Hurst PR, McNatty KP. 1995. Expression of IGF-I mRNA in the ovine ovary. J Mol Endocrinol, 15:251-258.
Lima IM, Brito IR, Rossetto R, Duarte AB, Rodrigues GQ, Saraiva MV, Costa JJ, Donato MA, Peixoto CA, Silva JR, de Figueiredo JR, Rodrigues AP. 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, 348:225-238.
Logan KA, Juengel JL, McNatty KP. 2002. Onset of steroidogenic enzyme gene expression during ovarian follicular development in sheep. Biol Reprod, 66:906-916.
Logan KA, McNatty KP, Juengel JL. 2003. Expression of wilms' tumor gene and protein localization during ovarian formation and follicular development in sheep. Biol Reprod, 68:635-643.
Lundy T, Smith P, O'Connell A, Hudson NL, McNatty KP. 1999. Populations of granulosa cells in small follicles of the sheep ovary. J Reprod Fertil, 115:251-262.
Matsuda F, Inoue N, Manabe N, Ohkura S. 2012. Follicular growth and atresia in mammalian ovaries: regulation by survival and death of granulosa cells. J Reprod Dev, 58:44-50.
McNatty KP, Henderson KM, Lun S, Heath DA, Ball K, Hudson NL, Fannin J, Gibb M, Kieboom LE, Smith P. 1985. Ovarian activity in Booroola X Romney ewes which have a major gene influencing their ovulation rate. J Reprod Fertil, 73:109-120.
McNatty KP, Heath DA, Hudson N, Clarke IJ. 1990. Effect of long-term hypophysectomy on ovarian follicle populations and gonadotrophin-induced adenosine cyclic 3',5'-monophosphate output by follicles from Booroola ewes with or without the F gene. J Reprod Fertil, 90:515-522.
McNatty KP, Juengel JL, Reader KL, Lun S, Myllymaa S, Lawrence SB, Western A, Meerasahib MF, Mottershead DG, Groome NP, Ritvos O, Laitinen MP. 2005. Bone morphogenetic protein 15 and growth differentiation factor 9 co-operate to regulate granulosa cell function in ruminants. Reproduction, 129:481-487.
McNatty KP, Hudson N, Smith P, Juengel JL. 2006. The effects of superovulating sheep with mutations in either the activin-like kinase (Alk6) or bone morphogenetic protein (BMP15) genes on ovulation rate and embryo production. J Reprod Dev, 52:S39-S43.
McNatty KP, Hudson NL, Whiting L, Reader KL, Lun S, Western A, Heath DA, Smith P, Moore LG, Juengel JL. 2007. The effects of immunizing sheep with different BMP15 or GDF9 peptide sequences on ovarian follicular activity and ovulation rate. Biol Reprod, 76:552-560.
McNatty KP, Heath DA, Hudson NL, Lun S, Juengel JL, Moore LG. 2009. Gonadotrophin-responsiveness of granulosa cells from bone morphogenetic protein 15 heterozygous mutant sheep. Reproduction, 138:545-551.
McNatty KP, Heath DA, Clark Z, Reader K, Juengel JL, Pitman JL. 2017. Ovarian characteristics in sheep with multiple fecundity genes. Reproduction, 153:233- 240.
Mihm M, Bleach EC. 2003. Endocrine regulation of ovarian antral follicle development in cattle. Anim Reprod Sci, 78:217-237.
Monniaux D, Clement F, Dalbies-Tran R, Estienne A, Fabre S, Mansanet C, Monget P. 2014. The ovarian reserve of primordial follicles and the dynamic reserve of antral growing follicles: what is the link? Biol Reprod, 90:85. doi: 10.1095/biolreprod.113.117077.
Myllymaa S, Pasternack A, Mottershead DG, Poutanen M, Pulkki MM, Pelliniemi LJ, Ritvos O, Laitinen MP. 2010. Inhibition of oocyte growth factors in vivo modulates ovarian folliculogenesis in neonatal and immature mice. Reproduction, 139:587-598.
Nicol L, Bishop SC, Pong-Wong R, Bendixen C, Holm LE, Rhind SM, McNeilly AS. 2009. Homozygosity for a single base-pair mutation in the oocyte-specific GDF9 gene results in sterility in Thoka sheep. Reproduction, 138:921-933.
Nilsson EE, Doraiswamy V, Skinner MK. 2003. Transforming growth factor-beta isoform expression during bovine ovarian antral follicle development. Mol Reprod Dev, 66:237-246.
Ortega HH, Marelli BE, Rey F, Amweg AN, Diaz PU, Stangaferro ML, Salvetti NR. 2015. Molecular aspects of bovine cystic ovarian disease pathogenesis. Reproduction, 149:R251-264.
Pankhurst MW. 2017. A putative role for antiMullerian hormone (AMH) in optimising ovarian reserve expenditure. J Endocrinol, 233:R1-R13.
Passos MJ, Vasconcelos GL, Silva AW, Brito IR, Saraiva MV, Magalhaes DM, Costa JJ, Donato MA, Ribeiro RP, Cunha EV, Peixoto CA, Campello CC, Figueiredo JR, van den Hurk R, Silva JR. 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, 79:1269-1277.
Pierre A, Pisselet C, Dupont J, Mandon-Pepin B, Monniaux D, Monget P, Fabre S. 2004. Molecular basis of bone morphogenetic protein-4 inhibitory action on progesterone secretion by ovine granulosa cells. J Mol Endocrinol, 33:805-817.
Pinto PHN, Balaro MFA, Souza-Fabjan JMG, Ribeiro LDS, Braganca GM, Leite CR, Arashiro EKN, de Moraes Silva K, Da Fonseca JF, Brandao FZ. 2018. Anti-Mullerian hormone and antral follicle count are more effective for selecting ewes with good potential for in vivo embryo production than the presence of FecG(E) mutation or eCG pre-selection tests. Theriogenology, 113:146-152.
Pohler KG, Geary TW, Atkins JA, Perry GA, Jinks EM, Smith MF. 2012. Follicular determinants of pregnancy establishment and maintenance. Cell Tissue Res, 349:649-664.
Price CA. 2016. Mechanisms of fibroblast growth factor signaling in the ovarian follicle. J Endocrinol, 228:R31-43. Reader KL, Heath DA, Lun S, McIntosh CJ, Western AH, Littlejohn RP, McNatty KP, Juengel JL. 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. Reader KL, Mottershead DG, Martin GA, Gilchrist RB, Heath DA, McNatty KP, Juengel JL. 2016. Signalling pathways involved in the synergistic effects of human growth differentiation factor 9 and bone morphogenetic protein 15. Reprod Fertil Dev, 28:491- 498.
Rodrigues GQ, Bertoldo MJ, Brito IR, Silva CM, Sales AD, Castro SV, Duffard N, Locatelli Y, Mermillod P, Lobo CH, Campello CC, Rodrigues AP, Freitas VJ, Figueiredo JR. 2014. Relative mRNA expression and immunolocalization for transforming growth factor-beta (TGF-beta) and their effect on in vitro development of caprine preantral follicles. In Vitro Cell Dev Biol Anim, 50:688-699.
Russell DL, Gilchrist RB, Brown HM, Thompson JG. 2016. Bidirectional communication between cumulus cells and the oocyte: old hands and new players? Theriogenology, 86:62-68.
Saraiva MV, Celestino JJ, Araujo VR, Chaves RN, Almeida AP, Lima-Verde IB, Duarte AB, Silva GM, Martins FS, Bruno JB, Matos MH, Campello CC, Silva JR, Figueiredo JR. 2011. Expression of folliclestimulating hormone receptor (FSHR) in goat ovarian follicles and the impact of sequential culture medium on in vitro development of caprine preantral follicles. Zygote, 19:205-214.
Scaramuzzi RJ, Baird DT, Campbell BK, Driancourt MA, Dupont J, Fortune JE, Gilchrist RB, Martin GB, McNatty KP, McNeilly AS, Monget P, Monniaux D, Vinoles C, Webb R. 2011. Regulation of folliculogenesis and the determination of ovulation rate in ruminants. Reprod Fertil Dev, 23:444-467.
Selvaraju S, Folger JK, Gupta PS, Ireland JJ, Smith GW. 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, 44:115-120.
Shackell GH, Hudson NL, Heath DA, Lun S, Shaw L, Condell L, Blay LR, McNatty KP. 1993. Plasma gonadotropin concentrations and ovarian characteristics in Inverdale ewes that are heterozygous for a major gene (FecX1) on the X chromosome that influences ovulation rate. Biol Reprod, 48:1150-1156.
Shimizu T, Kayamori T, Murayama C, Miyamoto A. 2012. Bone morphogenetic protein (BMP)-4 and BMP7 suppress granulosa cell apoptosis via different pathways: BMP-4 via PI3K/PDK-1/Akt and BMP-7 via PI3K/PDK-1/PKC. Biochem Biophys Res Commun, 417:869-873.
Shimizu T. 2016. Molecular and cellular mechanisms for the regulation of ovarian follicular function in cows. J Reprod Dev, 62:323-329.
Silva JR, van den Hurk R, Figueiredo JR. 2016. Ovarian follicle development in vitro and oocyte competence: advances and challenges for farm animals. Domest Anim Endocrinol, 55:123-135.
Skinner MK, Keski-Oja J, Osteen KG, Moses HL. 1987. Ovarian thecal cells produce transforming growth factor-beta which can regulate granulosa cell growth. Endocrinology, 121:786-792.
Smith PR. 2012. Development of the Rete Ovarii in the Sheep Ovary. Dunedin, New Zealand: Department of Anatomy, University of Otago. Thesis (Master of Science).
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.
Spicer LJ, Aad PY, Allen D, Mazerbourg S, Hsueh AJ. 2006. Growth differentiation factor-9 has divergent effects on proliferation and steroidogenesis of bovine granulosa cells. J Endocrinol, 189:329-339.
Spicer LJ, Aad PY, Allen DT, Mazerbourg S, Payne AH, Hsueh AJ. 2008. Growth differentiation factor 9 (GDF9) stimulates proliferation and inhibits steroidogenesis by bovine theca cells: influence of follicle size on responses to GDF9. Biol Reprod, 78:243-253.
Tisdall DJ, Hudson N, Smith P, McNatty KP. 1994. Localization of ovine follistatin and alpha and beta A inhibin mRNA in the sheep ovary during the oestrous cycle. J Mol Endocrinol, 12:181-193.
Tisdall DJ, Watanabe K, Hudson NL, Smith P, McNatty KP. 1995. FSH receptor gene expression during ovarian follicle development in sheep. J Mol Endocrinol, 15:273-281.
Tisdall DJ, Quirke LD, Smith P, McNatty KP. 1997. Expression of the ovine stem cell factor gene during folliculogenesis in late fetal and adult ovaries. J Mol Endocrinol, 18:127-135.
Vasconcelos GL, Saraiva MV, Costa JJ, Passos MJ, Silva AW, Rossi RO, Portela AM, Duarte AB, Magalhaes-Padilha DM, Campelo CC, Figueiredo JR, van den Hurk R, Silva JR. 2013. Effects of growth differentiation factor-9 and FSH on in vitro development, viability and mRNA expression in bovine preantral follicles. Reprod Fertil Dev, 25:1194-1203.
Wandji SA, Pelletier G, Sirard MA. 1992. Ontogeny and cellular localization of 125I-labeled basic fibroblast growth factor and 125I-labeled epidermal growth factor binding sites in ovaries from bovine fetuses and neonatal calves. Biol Reprod, 47:807-813.
Xu Z, Garverick HA, Smith GW, Smith MF, Hamilton SA, Youngquist RS. 1995. Expression of follicle-stimulating hormone and luteinizing hormone receptor messenger ribonucleic acids in bovine follicles during the first follicular wave. Biol Reprod, 53:951- 957.
Young JM, Juengel JL, Dodds KG, Laird M, Dearden PK, McNeilly AS, McNatty KP, Wilson T. 2008. The activin receptor-like kinase 6 Booroola mutation enhances suppressive effects of bone morphogenetic protein 2 (BMP2), BMP4, BMP6 and growth and differentiation factor-9 on FSH release from ovine primary pituitary cell cultures. J Endocrinol, 196:251-261.
Young JM, McNeilly AS. 2010. Theca: the forgotten cell of the ovarian follicle. Reproduction, 140:489-504.
Zheng X, Price CA, Tremblay Y, Lussier JG, Carriere PD. 2008. Role of transforming growth factor-beta1 in gene expression and activity of estradiol and progesterone-generating enzymes in FSHstimulated bovine granulosa cells. Reproduction, 136:447-457.
Zheng X, Boerboom D, Carriere PD. 2009. Transforming growth factor-beta1 inhibits luteinization and promotes apoptosis in bovine granulosa cells. Reproduction, 137:969-977.