Regulation of ovulation rate in mammals: contribution of sheep genetic models

Stéphane Fabre,Elisa Di Pasquale,Loys Bodin,Philippe Monget,Danielle Monniaux,Alice Pierre,Philippe Mulsant,Luca Persani

doi:10.1186/1477-7827-4-20

Abstract

Ovarian folliculogenesis in mammals from the constitution of primordial follicles up to ovulation is a reasonably well understood mechanism. Nevertheless, underlying mechanisms that determine the number of ovulating follicles were enigmatic until the identification of the fecundity genes affecting ovulation rate in sheep, bone morphogenetic protein-15 (BMP-15), growth and differentiation factor-9 (GDF-9) and BMP receptor-1B (BMPR-1B). In this review, we focus on the use of these sheep genetic models for understanding the role of the BMP system as an intra-ovarian regulator of follicular growth and maturation, and finally, ovulation rate.

Highlights

The general mechanism of ovarian folliculogenesis in mammals is reasonably well understood, implying a complex endocrine dialog between the central nervous system and the ovary, and various intraovarian paracrine regulations
Underlying mechanisms that determine the number of ovulating follicles were enigmatic until the identification of the fecundity genes affecting ovulation rate in sheep, bone morphogenetic protein-15 (BMP-15), growth and differentiation factor-9 (GDF-9) and Bone Morphogenetic Protein (BMP) receptor-1B (BMPR-1B)
We focus on the use of these sheep genetic models for understanding the role of the BMP system as an intra-ovarian regulator of follicular growth and maturation, and ovulation rate

Summary

Introduction

The general mechanism of ovarian folliculogenesis in mammals is reasonably well understood, implying a complex endocrine dialog between the central nervous system and the ovary, and various intraovarian paracrine regulations. This loss in receptor activity is illustrated by the fact that granulosa cells from homozygous FecBB carrier ewes are less sensitive to the action of BMP-4 on proliferation and inhibition of progesterone production than those from non-carrier ewes [21,57] In sheep, it seems that a decrease in BMP system activity leads to an increase in ovulation rate. In the presence of loss of function mutations, the BMP inhibiting action on the FSH pathway in granulosa cells is decreased, enabling a higher FSH sensitivity [5,65] and an enhanced expression of FSH-dependent markers of differentiation such as steroidogenic enzymes genes, inhibin/activin subunits and LH receptor in granulosa cells of antral follicles [63]. The answers to these questions are part of future field of investigation for the years to come

Conclusion

Davis GH