The final stages of dominant follicle selection in cattle

The final stages of ovarian follicle growth in cattle are typically characterized by the ultrasound-detectable emergence of a cohort of small (3-5mm in diameter) antral follicles, followed by a selection process during which the number of follicles continuing to grow decreases. Finally, only one follicle (the dominant follicle; DF) shows an enhanced growth rate and estradiol synthesis when it attains 8.5mm compared to its closest competitor (the largest subordinate follicle; SF). Cohort emergence is caused by a transient FSH rise, while DF selection occurs during declining FSH indicating differential FSH dependence of DF and SF. In order to elucidate the mechanisms underlying DF survival or SF atresia, this review aims to (i) describe follicular changes in the local production and regulation of members of the inhibin family of proteins and the insulin-like growth factor (IGF) system in relation to FSH deprivation leading to DF selection, and (ii) develop a model for DF selection outlining the putative involvement of inhibins, activin and follistatin on the one hand, and bioavailable IGFs regulated by IGF binding proteins (IGFBPs) and IGFBP proteases on the other hand. It is concluded, that the first indications of differential FSH dependence are seen within 33h of the FSH peak, and high amounts of precursor forms of inhibin and free activin, and low amounts of the lower molecular weight (MW) IGFBPs are related to follicle survival in terms of enhanced growth and estradiol synthesis, and suppression of granulosa cell apoptosis. In addition, maintenance of low amounts of intrafollicular IGFBP4 may constitute an important mechanism in the future DF to attain FSH independence.