Mechanisms regulating follicle selection in ruminants: lessons learned from multiple ovulation models

Area of Science:

• Reproductive biology
• Endocrinology
• Genetics

Background:

• Follicle selection is crucial for female reproduction and assisted reproductive technologies.
• Current understanding emphasizes FSH, LH, and IGF family roles, but TGF-ß family members, especially BMP15 and GDF9, are increasingly recognized for their impact on ovulation rates.
• Mutations in BMP15, GDF9, or BMPR1B (Booroola fecundity gene) affect ovulation rates and follicle development.

Purpose of the Study:

• To review mechanisms of follicle selection in ruminants, focusing on high fecundity genotypes.
• To highlight the role of BMP15/GDF9 signaling pathways in regulating follicle selection and ovulation rate.
• To present a new physiological model for multiple dominant follicle selection based on BMP15/GDF9 signaling.

Main Methods:

• Review of existing literature on follicle selection, endocrine, paracrine, and autocrine mechanisms.
• Analysis of high fecundity genotypes in sheep (Booroola) and cattle (Trio).
• Focus on intercellular signaling between oocyte and granulosa cells, including BMP15, GDF9, and SMAD6.

Main Results:

• Mutations in BMP15 or GDF9 increase ovulation rate in heterozygotes and cause abnormalities in homozygotes.
• The Trio genotype in cattle involves increased SMAD6 expression, an inhibitor of BMP15/GDF9 signaling, providing insights into multiple ovulation.
• A new model suggests altered BMP15/GDF9 signaling leads to earlier acquisition of dominance at smaller follicle sizes, with multiple follicles dominating sequentially.

Conclusions:

• The BMP15/GDF9 signaling pathway is a key regulator of follicle selection and ovulation rate in ruminants.
• Altered signaling, as seen in high fecundity genotypes, can lead to multiple dominant follicle selection and increased ovulation.
• The proposed model provides a framework for understanding the physiological basis of increased ovulation rates in carriers of fecundity alleles.