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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.

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Citations

This article has been cited 4 times.
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