The role of BMP signalling pathway in the regulation of ovarian follicle development

Abstract

Bone morphogenetic proteins (BMPs) regulation of ovarian function has been investigated in several animal models, demonstrating their role in primordial germ cell formation, primordial-to-primary follicle recruitment, follicle development, seroidogenesis and ovulation. However, the mechanism by which BMPs regulate individual processes of ovarian function is not well understood. The aim of this study was to investigate the effect of the BMP receptor mutation in Booroola sheep on primordial follicle formation and rate of recruitment in comparison to that in normal merino sheep in vivo. Whole ovaries from Booroola and merino sheep at birth, 1.5 years and 5 years of age were obtained by bilateral ovariectomy and processed for the quantification of primordial and primary follicles using computerised stereological methods (Stereo Investigator Software Version 7, MicroBrightField, Inc.) and JMP 6 statistical package (SAS Institute Inc, 2005). Regardless of animal strain, the overall absolute number of primordial and primary follicles per ovary of newborn sheep was considerably higher than in the 1.5 and 5-year old ewes. Log transformed data analyses revealed that the total number of primordial follicles in newborn Booroola sheep was significantly (P=0.0065) lower than in merino of the same age. At 1.5 years a trend showing a considerable reversal in the number of primordial follicles was observed in Booroola ewes, which then significantly (p<0.0036) increased at 5 years of age. The rate of primordial follicle recruitment was substantially lower in Booroola ewes compared with that in merino, as reflected in the difference in the absolute number of primordial follicles remaining at 1.5 and 5 years of age. Immediately after birth, the mean total number of primordial follicles in Booroola strain was only 36% of that present in the merino strain. This ratio became 207% and 367% at 1.5 and 5 years, respectively. The ratios of primordial follicle consumption in Booroola ewes were 51% and 66% up to the age of 1.5 and 5 years respectively compared to 92% and 97% of primordial follicles have been used in merino ewes. On the other hand, the numbers of primary follicles per ovary in newbord animals was similar in both sheep strains. However, at 1.5 years, Booroola ewes possess more primary follicles than merino, and the absolute number of primary follicles present at 1.5 years was equal to 26% of the number present at birth, compared with only 8% of primary follicles present in merino ewes. At 5 years of age the primary follicles were not counted in either animal strain. These findings suggest that attenuation of the intraovarian signaling pathway of BMPs may in fact be a successful means of rationalizing follicle consumption, preventing unnecessary loss of follicles from the initial follicle pool, hence increasing productive age and fertility.