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Home / Equine Research Bank / BMC Vet Res / Roles of GDF9 and BMP15 in equine follicular development: in...
BMC veterinary research2025; 21(1); 292; doi: 10.1186/s12917-025-04744-6

Roles of GDF9 and BMP15 in equine follicular development: in vivo content and in vitro effects of IGF1 and cortisol on granulosa cells.

Abstract: In horses, the mechanisms behind ovarian follicle growth and oocyte maturation remain largely unknown. In other species, oocyte-secreted factors growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) have been related to the acquisition of developmental competence and to interaction with granulosa cells for the regulation of follicle development. This study assessed the expression and localization of GDF9 in the equine ovary, and its possible relationship with granulosa cell function. Results: Using custom-made antibodies, GDF9 protein was localized in oocytes from the primary follicle stage onwards. Together with BMP15, its intrafollicular concentration was higher in small antral follicles compared to larger ones (P < 0.05). Negative correlations were observed between intrafollicular BMP15 concentration and estradiol sulfate (E2S) (r = -0.36, P = 0.048), as well as between BMP15 and E2S/P4 ratio (r = -0.37, P = 0.046). In vivo, equine granulosa cells showed increasing mRNA expression of genes involved in steroidogenesis (STAR and HSD3B2) and cell proliferation (KI67) with increasing follicle size, while expression of GDF9 and of apoptosis-related genes (BCL2 and CASP3) were not affected by follicle size. Simultaneous stimulation of granulosa cells in vitro with IGF1 and cortisol significantly increased HSD3B2 and CYP19A1 transcriptional levels, as well as E2 concentration in culture media, while IGF1-induced P4 secretion was suppressed in the presence of cortisol. Blocking the stimulatory effect of IGF1 on E2, E2S and P4 by H89 was associated with increased GDF9 mRNA levels and reduced STAR, PCNA, KI67 and BCL2 mRNA expression. Significant negative correlations of GDF9 with STAR and PCNA mRNA, respectively, were seen in vivo and in vitro. Conclusions: Together, our results show GDF9 localization and expression in the equine ovary and a temporal relationship with steroidogenesis and cell proliferation within the surrounding granulosa cells. Moreover, results of the in vitro study suggest a supporting role of cortisol during follicle maturation. Our study sheds light on possible mechanisms for the regulation of ovarian function in horses using GDF9.
© 2025. The Author(s).
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Publication Date: 2025-04-27 PubMed ID: 40289073PubMed Central: PMC12034142DOI: 10.1186/s12917-025-04744-6Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates the roles of certain proteins in horse ovarian follicle growth and oocyte maturation. The study revealed the presence of the proteins – growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) – in horse ovaries, showing a correlation between these proteins and cellular processes like steroidogenesis and cell proliferation. The research also suggests cortisol, a hormone, may play a supporting role in follicle maturation.

Research Focus

  • The research primarily aimed to investigate the roles of GDF9 and BMP15 in the development of ovarian follicles in horses. The roles of these oocyte-secreted factors are known in other species, but not fully understood in horses.
  • The study also tried to understand how the proteins GDF9 and BMP15 interact with granulosa cells – cells surrounding the ovum in the ovarian follicle – to regulate follicle growth.

Observations and Findings

  • Researchers localized GDF9 presence to oocytes from the primary follicle stage onwards using custom-made antibodies. They also found that the concentration of GDF9 and BMP15 was higher in smaller follicles compared to larger ones.
  • Negative correlations were identified between the BMP15 concentration and estradiol sulfate (E2S), and between BMP15 and E2S/P4 ratio.
  • In vivo, it was observed that mRNA expression of genes involved in steroidogenesis processes (STAR and HSD3B2) and cell proliferation (KI67) increased with follicle size. However, the expression of GDF9 – along with apoptosis-related genes BCL2 and CASP3 – remained unaffected by follicle size.

In vitro Experiments and Results

  • During in vitro stimulation of granulosa cells with the hormone IGF1 and cortisol, there was a significant increase in transcript levels of HSD3B2 and CYP19A1, and concentration of E2 in culture media. However, IGF1-induced P4 secretion was suppressed by cortisol.
  • Blocking IGF1’s stimulatory effect on E2, E2S, and P4 led to an increase in GDF9 mRNA levels and reduced mRNA expression of STAR, PCNA, KI67, and BCL2. There was a significant negative correlation between GDF9 with STAR and PCNA mRNA, both in vivo and in vitro.

Conclusions and Implications

  • Overall, the study identified the presence and expression of GDF9 in the horse ovary, and demonstrated a temporal relationship between GDF9 and steroidogenesis, cell proliferation processes within surrounding granulosa cells.
  • The in vitro study suggested that cortisol may have a supportive role during follicle maturation.
  • The research contributes to a better understanding of the regulation of ovarian function in horses, especially the role of the GDF9 protein, thus potentially opening up new ways of optimising reproductive strategies in horses and other species.

Cite This Article

APA
Samie KA, Kowalewski MP, Schuler G, Gastal GDA, Bollwein H, Scarlet D. (2025). Roles of GDF9 and BMP15 in equine follicular development: in vivo content and in vitro effects of IGF1 and cortisol on granulosa cells. BMC Vet Res, 21(1), 292. https://doi.org/10.1186/s12917-025-04744-6

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 21
Issue: 1
Pages: 292
PII: 292

Researcher Affiliations

Samie, Kosar Abbasi
  • Institute of Veterinary Anatomy, Vetsuisse Faculty Zurich, Winterthurerstrasse 260, Zurich, 8057, Switzerland.
Kowalewski, Mariusz P
  • Institute of Veterinary Anatomy, Vetsuisse Faculty Zurich, Winterthurerstrasse 260, Zurich, 8057, Switzerland.
Schuler, Gerhard
  • Veterinary Clinic for Reproductive Medicine and Neonatology, Justus-Liebig-University, Frankfurter Strasse 106, 35392, Giessen, Germany.
Gastal, Gustavo D A
  • Instituto Nacional de Investigación Agropecuaria INIA, Estacion Experimental La Estanzela, Ruta 50 km 11, Cologne, Colonia, 39173, Uruguay.
Bollwein, Heinrich
  • Clinic of Reproductive Medicine, Vetsuisse Faculty Zurich, Winterthurerstrasse 260, Zurich, 8057, Switzerland.
  • AgroVet-Strickhof, Vetsuisse Faculty, Eschikon, Lindau, Switzerland.
Scarlet, Dragos
  • Institute of Veterinary Anatomy, Vetsuisse Faculty Zurich, Winterthurerstrasse 260, Zurich, 8057, Switzerland. dragos.scarlet@uzh.ch.
  • Clinic of Reproductive Medicine, Vetsuisse Faculty Zurich, Winterthurerstrasse 260, Zurich, 8057, Switzerland. dragos.scarlet@uzh.ch.
  • AgroVet-Strickhof, Vetsuisse Faculty, Eschikon, Lindau, Switzerland. dragos.scarlet@uzh.ch.

MeSH Terms

  • Animals
  • Female
  • Horses / physiology
  • Growth Differentiation Factor 9 / metabolism
  • Growth Differentiation Factor 9 / genetics
  • Granulosa Cells / drug effects
  • Granulosa Cells / metabolism
  • Granulosa Cells / physiology
  • Bone Morphogenetic Protein 15 / metabolism
  • Bone Morphogenetic Protein 15 / genetics
  • Ovarian Follicle / growth & development
  • Ovarian Follicle / metabolism
  • Ovarian Follicle / drug effects
  • Insulin-Like Growth Factor I / pharmacology
  • Insulin-Like Growth Factor I / metabolism
  • Hydrocortisone / pharmacology
  • Estradiol / analogs & derivatives
  • Estradiol / metabolism

Grant Funding

  • FK-21-059 / Universitu00e4t Zu00fcrich

Conflict of Interest Statement

Declarations. Competing interests: The authors declare no competing interests.

References

This article includes 86 references
  1. Eppig JJ, Schultz RM, O’Brien M, Chesnel F. Relationship between the developmental programs controlling nuclear and cytoplasmic maturation of mouse oocytes.. Dev Biol 1994;164(1):1–9.
    pubmed: 8026614
  2. Dumesic DA, Meldrum DR, Katz-Jaffe MG, Krisher RL, Schoolcraft WB. Oocyte environment: follicular fluid and cumulus cells are critical for oocyte health.. Fertil Steril 2015;103(2):303–16.
    pubmed: 25497448
  3. Macaulay AD, Gilbert I, Caballero J, Barreto R, Fournier E, Tossou P. The gametic synapse: RNA transfer to the bovine Oocyte1.. Biol Reprod 2014;91(4).
    pubmed: 25143353
  4. Alam MH, Miyano T. Interaction between growing oocytes and granulosa cells in vitro.. Reproductive Med Biology 2020;19(1):13–23.
    pmc: PMC6955591pubmed: 31956281
  5. Knight PG, Glister C. Potential local regulatory functions of inhibins, activins and follistatin in the ovary.. Reproduction 2001;121(4):503–12.
    pubmed: 11277869
  6. Hillier S. Current concepts of the roles of follicle stimulating hormone and luteinizing hormone in folliculogenesis.. Hum Reprod 1994;9(2):188–91.
    pubmed: 8027271
  7. Fru KN, VandeVoort CA, Chaffin CL. Mineralocorticoid synthesis during the periovulatory interval in macaques.. Biol Reprod 2006;75(4):568–74.
    pubmed: 16837642
  8. Hedberg Y, Dalin AM, Forsberg M, Lundeheim N, Sandh G, Hoffmann B. Effect of ACTH (tetracosactide) on steroid hormone levels in the mare: part B: effect in ovariectomized mares (including estrous behavior).. Anim Reprod Sci 2007;100(1):92–106.
    pubmed: 16860499
  9. Hennet ML, Combelles CM. The antral follicle: a microenvironment for oocyte differentiation.. Int J Dev Biol 2012;56(10–12):819–31.
    pubmed: 23417404
  10. Costermans NGJ, Soede NM, van Tricht F, Blokland M, Kemp B, Keijer J. Follicular fluid steroid profile in sows: relationship to follicle size and oocyte quality†.. Biol Reprod 2020;102(3):740–9.
    pmc: PMC7068110pubmed: 31786607
  11. Poretsky L, Cataldo NA, Rosenwaks Z, Giudice LC. The insulin-related ovarian regulatory system in health and disease.. Endocr Rev 1999;20(4):535–82.
    pubmed: 10453357
  12. Makarevich A, Sirotkin A, Chrenek P, Bulla J, Hetenyi L. The role of IGF-I, cAMP/protein kinase A and MAP-kinase in the control of steroid secretion, Cyclic nucleotide production, granulosa cell proliferation and preimplantation embryo development in rabbits.. J Steroid Biochem Mol Biol 2000;73(3–4):123–33.
    pubmed: 10925211
  13. Mani AM, Fenwick MA, Cheng Z, Sharma MK, Singh D, Wathes DC. IGF1 induces up-regulation of steroidogenic and apoptotic regulatory genes via activation of phosphatidylinositol-dependent kinase/akt in bovine granulosa cells.. Reproduction 2010;139(1):139.
    pubmed: 19819918
  14. Davidson TR, Chamberlain CS, Bridges TS, Spicer LJ. Effect of follicle size on in vitro production of steroids and insulin-like growth factor (IGF)-I, IGF-II, and the IGF-binding proteins by equine ovarian granulosa cells.. Biol Reprod 2002;66(6):1640–8.
    pubmed: 12021042
  15. Short R. Steroids present in the follicular fluid of the mare.. J Endocrinol 1960;20:147–56.
    pubmed: 14446192
  16. Ginther OJ, Utt MD, Beg MA. Follicle deviation and diurnal variation in Circulating hormone concentrations in mares.. Anim Reprod Sci 2007;100(1–2):197–203.
    pubmed: 17000062
  17. Scarlet D, Ille N, Ertl R, Alves BG, Gastal GDA, Paiva SO. Glucocorticoid metabolism in equine follicles and oocytes.. Domest Anim Endocrinol 2017;59:11–22.
    pubmed: 27866059
  18. Acosta TJ, Tetsuka M, Matsui M, Shimizu T, Berisha B, Schams D. In vivo evidence that local cortisol production increases in the preovulatory follicle of the cow.. J Reprod Dev 2005;51(4):483–9.
    pubmed: 15947453
  19. Harlow CR, Jenkins JM, Winston RM. Increased follicular fluid total and free cortisol levels during the luteinizing hormone surge.. Fertil Steril 1997;68(1):48–53.
    pubmed: 9207583
  20. Nakanishi T, Okamoto A, Ikeda M, Tate S, Sumita M, Kawamoto R. Cortisol induces follicle regression, while FSH prevents cortisol-induced follicle regression in pigs.. Mol Hum Reprod 2021;27(7).
    pubmed: 34057472
  21. Yuan HJ, Li ZB, Zhao XY, Sun GY, Wang GL, Zhao YQ. Glucocorticoids impair oocyte competence and trigger apoptosis of ovarian cells via activating the TNF-α system.. Reproduction 2020;160(1):129–40.
    pubmed: 32485668
  22. Sasson R, Tajima K, Amsterdam A. Glucocorticoids protect against apoptosis induced by serum deprivation, Cyclic adenosine 3’,5’-monophosphate and p53 activation in immortalized human granulosa cells: involvement of Bcl-2.. Endocrinology 2001;142(2):802–11.
    pubmed: 11159853
  23. Davis KA, Klohonatz KM, Mora DSO, Twenter HM, Graham PE, Pinedo P. Effects of immunization against bone morphogenetic protein-15 and growth differentiation factor-9 on ovarian function in mares.. Anim Reprod Sci 2018;192:69–77.
    pubmed: 29534827
  24. Juengel JL, Hudson NL, Berg M, Hamel K, Smith P, Lawrence SB. Effects of active immunization against growth differentiation factor 9 and/or bone morphogenetic protein 15 on ovarian function in cattle.. Reproduction 2009;138(1):107–14.
    pubmed: 19439562
  25. Juengel JL, Hudson NL, Whiting L, McNatty KP. Effects of immunization against bone morphogenetic protein 15 and growth differentiation factor 9 on ovulation rate, fertilization, and pregnancy in Ewes.. Biol Reprod 2004;70(3):557–61.
    pubmed: 14585806
  26. Juengel J, McNatty K. The role of proteins of the transforming growth factor-β superfamily in the intraovarian regulation of follicular development.. Hum Reprod Update 2005;11(2):144–61.
    pubmed: 15705960
  27. Guéripel X, Brun V, Gougeon A. 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 2006;75(6):836–43.
    pubmed: 16943361
  28. Carabatsos MJ, Elvin J, Matzuk MM, Albertini DF. Characterization of oocyte and follicle development in growth differentiation factor-9-deficient mice.. Dev Biol 1998;204(2):373–84.
    pubmed: 9882477
  29. Liu C, Peng J, Matzuk MM, Yao HH. Lineage specification of ovarian Theca cells requires multicellular interactions via oocyte and granulosa cells.. Nat Commun 2015;6:6934.
    pmc: PMC4413950pubmed: 25917826
  30. Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, Matzuk MM. Growth differentiation factor-9 is required during early ovarian folliculogenesis.. Nature 1996;383(6600):531–5.
    pubmed: 8849725
  31. Sun R, Lei L, Cheng L, Jin Z, Zu S, Shan Z. Expression of GDF-9, BMP-15 and their receptors in mammalian ovary follicles.. J Mol Histol 2010;41:325–32.
    pubmed: 20857181
  32. Hosoe M, Kaneyama K, Ushizawa K, Hayashi K-g, Takahashi T. Quantitative analysis of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) gene expression in calf and adult bovine ovaries.. Reproductive Biology Endocrinol 2011;9:1–8.
    pmc: PMC3064654pubmed: 21401961
  33. Aguiar FLN, Gastal GDA, Ishak GM, Gastal MO, Teixeira DIA, Feugang JM. Effects of FSH addition to an enriched medium containing insulin and EGF after long-term culture on functionality of equine ovarian biopsy tissue.. Theriogenology 2017;99:124–33.
    pubmed: 28708493
  34. Gong Y, Li-Ling J, Xiong D, Wei J, Zhong T, Tan H. Age-related decline in the expression of GDF9 and BMP15 genes in follicle fluid and granulosa cells derived from poor ovarian responders.. J Ovarian Res 2021;14:1–10.
    pmc: PMC7780377pubmed: 33397408
  35. Silva J, Van den Hurk R, Van Tol H, Roelen B, Figueiredo J. Expression of growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15), and BMP receptors in the ovaries of goats.. Mol Reprod Development: Incorporating Gamete Res 2005;70(1):11–9.
    pubmed: 15515056
  36. Miyoshi T, Otsuka F, Nakamura E, Inagaki K, Ogura-Ochi K, Tsukamoto N. Regulatory role of kit ligand–c-kit interaction and oocyte factors in steroidogenesis by rat granulosa cells.. Mol Cell Endocrinol 2012;358(1):18–26.
    pubmed: 22366471
  37. Elvin JA, Clark AT, Wang P, Wolfman NM, Matzuk MM. Paracrine actions of growth differentiation factor-9 in the mammalian ovary.. Mol Endocrinol 1999;13(6):1035–48.
    pubmed: 10379900
  38. Gui L-M, Joyce IM. RNA interference evidence that growth differentiation factor-9 mediates oocyte regulation of cumulus expansion in mice.. Biol Reprod 2005;72(1):195–9.
    pubmed: 15385414
  39. Su Y-Q, Sugiura K, Wigglesworth K, O’Brien MJ, Affourtit JP, Pangas SA. Oocyte regulation of metabolic cooperativity between mouse cumulus cells and oocytes: BMP15 and GDF9 control cholesterol biosynthesis in cumulus cells.. 2008.
    pubmed: 18045843
  40. Gilchrist RB, Ritter L, Cranfield M, Jeffery L, Amato F, Scott S. Immunoneutralization of growth differentiation factor 9 reveals it partially accounts for mouse oocyte mitogenic activity.. Biol Reprod 2004;71(3):732–9.
    pubmed: 15128595
  41. Huang Q, Cheung AP, Zhang Y, Huang H-F, Auersperg N, Leung PC. Effects of growth differentiation factor 9 on cell cycle regulators and ERK42/44 in human granulosa cell proliferation.. Am J Physiology-Endocrinology Metabolism 2009;296(6):E1344–53.
    pubmed: 19366876
  42. Spicer LJ, Aad PY, Allen D, Mazerbourg S, Hsueh AJ. Growth differentiation factor-9 has divergent effects on proliferation and steroidogenesis of bovine granulosa cells.. J Endocrinol 2006;189(2):329–39.
    pubmed: 16648300
  43. Shi F-T, Cheung AP, Huang H-F, Leung PC. Effects of endogenous growth differentiation factor 9 on activin A-induced inhibin B production in human granulosa-lutein cells.. J Clin Endocrinol Metabolism 2009;94(12):5108–16.
    pubmed: 19846738
  44. Roy S, Gandra D, Seger C, Biswas A, Kushnir VA, Gleicher N. Oocyte-derived factors (GDF9 and BMP15) and FSH regulate AMH expression via modulation of H3K27AC in granulosa cells.. Endocrinology 2018;159(9):3433–45.
    pmc: PMC6112599pubmed: 30060157
  45. Stefaniuk-Szmukier M, Ropka-Molik K, Zagrajczuk A, Piórkowska K, Szmatoła T, Łuszczyński J. Genetic variability in equine GDF9 and BMP15 genes in Arabian and thoroughbred mares.. Annals Anim Sci 2018;18(1):39–52.
  46. Moor R, Hay MF, Dott H, Cran D. Macroscopic identification and steroidogenic function of atretic follicles in sheep.. J Endocrinol 1978;77(3):309–18.
    pubmed: 660074
  47. Nowak M, Boos A, Kowalewski MP. Luteal and hypophyseal expression of the canine relaxin (RLN) system during pregnancy: implications for luteotropic function.. PLoS ONE 2018;13(1):e0191374.
    pmc: PMC5783387pubmed: 29364921
  48. Tavares Pereira M, Schuler G, Aslan S, Payan-Carreira R, Reichler IM, Reynaud K. Utero-placental expression and functional implications of HSD11B1 and HSD11B2 in canine pregnancy†.. Biol Reprod 2023;108(4):645–58.
    pubmed: 36722005
  49. Graubner FR, Tavares Pereira M, Boos A, Kowalewski MP. Canine decidualization in vitro: extracellular matrix modification, progesterone mediated effects and selective blocking of prostaglandin E2 receptors.. J Reprod Dev 2020;66(4):319–29.
    pmc: PMC7470904pubmed: 32201411
  50. Kazemian A, Tavares Pereira M, Hoffmann B, Kowalewski MP. Antigestagens mediate the expression of decidualization markers, extracellular matrix factors and connexin 43 in decidualized dog uterine stromal (DUS) cells.. Animals 2022;12(7):798.
    pmc: PMC8996927pubmed: 35405788
  51. Hoffmann B, Gentz F, Failing K. Investigations into the course of progesterone-, oestrogen-and eCG-concentrations during normal and impaired pregnancy in the mare. 1996.
  52. Strecker H, Hachmann H, Seidel L. Der Radioimmunoassay (RIA), eine hochspezifische, extrem empfindliche quantitative Analysenmethode. 1979.
  53. Hoffmann B, Höveler R, Hasan SH, Failing K. Ovarian and pituitary function in dogs after hysterectomy.. J Reprod Fertil 1992;96(2):837–45.
    pubmed: 1339862
  54. Spicer LJ, Chamberlain CS. Influence of cortisol on insulin- and insulin-like growth factor 1 (IGF-1)-induced steroid production and on IGF-1 receptors in cultured bovine granulosa cells and thecal cells.. Endocrine 1998;9(2):153–61.
    pubmed: 9867249
  55. Kowalewski MP, Dyson MT, Boos A, Stocco DM. Vasoactive intestinal peptide (VIP)-mediated expression and function of steroidogenic acute regulatory protein (StAR) in granulosa cells.. Mol Cell Endocrinol 2010;328(1–2):93–103.
    pmc: PMC5010784pubmed: 20655982
  56. Manna PR, Chandrala SP, King SR, Jo Y, Counis R, Huhtaniemi IT. Molecular mechanisms of Insulin-like growth Factor-I mediated regulation of the steroidogenic acute regulatory protein in mouse Leydig cells.. Mol Endocrinol 2006;20(2):362–78.
    pubmed: 16166197
  57. Scarlet D, Ertl R, Aurich C, Steinborn R. The orthology clause in the next generation sequencing era: novel reference genes identified by RNA-seq in humans improve normalization of neonatal equine ovary RT-qPCR data.. PLoS ONE 2015;10(11):e0142122.
    pmc: PMC4633174pubmed: 26536597
  58. Jackowska M, Kempisty B, Woźna M, Piotrowska H, Antosik P, Zawierucha P. Differential expression of GDF9, TGFB1, TGFB2 and TGFB3 in Porcine oocytes isolated from follicles of different size before and after culture in vitro.. Acta Veterinaria Hungarica 2013;61(1):99–115.
    pubmed: 23439295
  59. Lin ZL, Li YH, Xu YN, Wang QL, Namgoong S, Cui XS. Effects of growth differentiation factor 9 and bone morphogenetic protein 15 on the in vitro maturation of Porcine oocytes.. Reprod Domest Anim 2014;49(2):219–27.
    pubmed: 24313324
  60. Cadenas J, Poulsen LC, Nikiforov D, Grøndahl ML, Kumar A, Bahnu K. Regulation of human oocyte maturation in vivo during the final maturation of follicles.. Hum Reprod 2023;38(4):686–700.
    pubmed: 36762771
  61. Kristensen SG, Kumar A, Mamsen LS, Kalra B, Pors SE, Bøtkjær JA. Intrafollicular concentrations of the Oocyte-secreted factors GDF9 and BMP15 vary inversely in polycystic ovaries.. J Clin Endocrinol Metab 2022;107(8):e3374–83.
    pmc: PMC9282257pubmed: 35511085
  62. Sanfins A, Rodrigues P, Albertini DF. GDF-9 and BMP-15 direct the follicle symphony.. J Assist Reprod Genet 2018;35(10):1741–50.
    pmc: PMC6150895pubmed: 30039232
  63. Gode F, Gulekli B, Dogan E, Korhan P, Dogan S, Bige O. Influence of follicular fluid GDF9 and BMP15 on embryo quality.. Fertil Steril 2011;95(7):2274–8.
    pubmed: 21496799
  64. Brown KA, Doré M, Lussier JG, Sirois J. Human chorionic gonadotropin-dependent up-regulation of genes responsible for Estrogen sulfoconjugation and export in granulosa cells of luteinizing preovulatory follicles.. Endocrinology 2006;147(9):4222–33.
    pubmed: 16763059
  65. Vitt U, Hayashi M, Klein C, Hsueh A. Growth differentiation factor-9 stimulates proliferation but suppresses the follicle-stimulating hormone-induced differentiation of cultured granulosa cells from small antral and preovulatory rat follicles.. Biol Reprod 2000;62(2):370–7.
    pubmed: 10642575
  66. Spicer LJ, Aad PY, Allen DT, Mazerbourg S, Payne AH, Hsueh AJ. Growth differentiation factor 9 (GDF9) stimulates proliferation and inhibits steroidogenesis by bovine Theca cells: influence of follicle size on responses to GDF9.. Biol Reprod 2008;78(2):243–53.
    pubmed: 17959852
  67. Palomino J, De los Reyes M. Temporal expression of GDF-9 and BMP-15 mRNAs in canine ovarian follicles.. Theriogenology 2016;86(6):1541–9.
    pubmed: 27341772
  68. Jacob JC, Gastal EL, Gastal MO, Carvalho GR, Beg MA, Ginther OJ. Temporal relationships and repeatability of follicle diameters and hormone concentrations within individuals in mares.. Reprod Domest Anim 2009;44(1):92–9.
    pubmed: 18954382
  69. Belin F, Goudet G, Duchamp G, Gérard N. Intrafollicular concentrations of steroids and steroidogenic enzymes in relation to follicular development in the mare.. Biol Reprod 2000;62(5):1335–43.
    pubmed: 10775185
  70. Kerban A, Boerboom D, Sirois J. Human chorionic gonadotropin induces an inverse regulation of steroidogenic acute regulatory protein messenger ribonucleic acid in Theca Interna and granulosa cells of equine preovulatory follicles.. Endocrinology 1999;140(2):667–74.
    pubmed: 9927292
  71. Boerboom D, Sirois J. Equine P450 cholesterol side-chain cleavage and 3 beta-hydroxysteroid dehydrogenase/delta(5)-delta(4) isomerase: molecular cloning and regulation of their messenger ribonucleic acids in equine follicles during the ovulatory process.. Biol Reprod 2001;64(1):206–15.
    pubmed: 11133676
  72. Mason JI, Keeney DS, Bird IM, Rainey WE, Morohashi K, Leers-Sucheta S. The regulation of 3 beta-hydroxysteroid dehydrogenase expression.. Steroids 1997;62(1):164–8.
    pubmed: 9029732
  73. Ben-Rafael Z, Benadiva CA, García CJ, Flickinger GL. Cortisol stimulation of estradiol and progesterone secretion by human granulosa cells is independent of follicle-stimulating hormone effects.. Fertil Steril 1988;49(5):813–6.
    pubmed: 3129316
  74. Kawate N, Inaba T, Mori J. Effects of cortisol on the amounts of estradiol-17β and progesterone secreted and the number of luteinizing hormone receptors in cultured bovine granulosa cells.. Anim Reprod Sci 1993;32(1):15–25.
  75. Jeon H, Choi Y, Brännström M, Akin J, Curry T, Jo M. Cortisol/glucocorticoid receptor: a critical mediator of the ovulatory process and luteinization in human periovulatory follicles.. Hum Reprod 2023;38(4):671–85.
    pmc: PMC10068287pubmed: 36752644
  76. Yong PY, Thong K, Andrew R, Walker BR, Hillier SG. Development-related increase in cortisol biosynthesis by human granulosa cells.. J Clin Endocrinol Metabolism 2000;85(12):4728–33.
    pubmed: 11134135
  77. Hardy K, Mora JM, Dunlop C, Carzaniga R, Franks S, Fenwick MA. Nuclear exclusion of SMAD2/3 in granulosa cells is associated with primordial follicle activation in the mouse ovary.. J Cell Sci 2018;131(17).
    pubmed: 30111581
  78. Orisaka M, Orisaka S, Jiang J-Y, Craig J, Wang Y, Kotsuji F. Growth differentiation factor 9 is antiapoptotic during follicular development from preantral to early antral stage.. Mol Endocrinol 2006;20(10):2456–68.
    pubmed: 16740654
  79. Dorrington JH, Bendell JJ, Lobb DK. Aromatase activity in granulosa cells: regulation by growth factors.. Steroids 1987;50(4–6):411–21.
    pubmed: 3144065
  80. Kadakia R, Arraztoa JA, Bondy C, Zhou J. Granulosa cell proliferation is impaired in the Igf1 null ovary.. Growth Horm IGF Res 2001;11(4):220–4.
    pubmed: 11735237
  81. Han Y, Chen Y, Yang F, Sun X, Zeng S. Mechanism underlying the stimulation by IGF-1 of LHCGR expression in Porcine granulosa cells.. Theriogenology 2021;169:56–64.
    pubmed: 33933758
  82. Wang R, Schneider S, Keppler OT, Li B, Rutz B, Ciotkowska A. ADP ribosylation factor 6 promotes contraction and proliferation, suppresses apoptosis and is specifically inhibited by NAV2729 in prostate stromal cells.. Mol Pharmacol 2021;100(4):356–71.
    pubmed: 34349027
  83. Zhang JL, Han X, Shan YJ, Zhang LW, Du M, Liu M. Effect of bovine lactoferrin and human lactoferrin on the proliferative activity of the osteoblast cell line MC3T3-E1 in vitro.. J Dairy Sci 2018;101(3):1827–33.
    pubmed: 29290425
  84. Regan SLP, Knight PG, Yovich JL, Leung Y, Arfuso F, Dharmarajan A. Granulosa cell apoptosis in the ovarian Follicle-A changing view.. Front Endocrinol (Lausanne) 2018;9:61.
    pmc: PMC5840209pubmed: 29551992
  85. Wischral A, Pastorello M, Gastal MO, Beg MA, Gastal EL. Hemodynamic, endocrine, and gene expression mechanisms regulating equine ovarian follicular and cellular development.. Mol Reprod Dev 2022;89(1):23–38.
    pubmed: 34911155
  86. Earnshaw WC, Martins LM, Kaufmann SH. Mammalian caspases: structure, activation, substrates, and functions during apoptosis.. Annu Rev Biochem 1999;68(1):383–424.
    pubmed: 10872455

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