Differentiation of dominant versus subordinate follicles in cattle

Selection of a dominant follicle, capable of ovulating, from among a cohort of similarly sized follicles is a critical transition in follicular develo pment. The mechanisms that regulate the selection of a species-specific num ber of dominant follicles for ovulation are not well understood. Cattle pro vide a very useful animal model for studies on follicular selection and dom inance. During the bovine estrous cycle, two or three sequential waves of f ollicular development occur, each producing a dominant follicle capable of ovulating if luteal regression occurs. Follicles are large enough to allow analysis of multiple endpoints within a single follicle, and follicular dev elopment and regression can be followed via ultrasonographic imaging. Chara cteristics of recruited and selected follicles, obtained at various times d uring the first follicular wave, have been determined in some studies, wher eas dominant and subordinate follicles have been compared around the time o f selection in others. As follicular recruitment proceeds, mRNA for P450 ar omatase increases. By the time of morphological selection, the dominant fol licle has much higher concentrations of estradiol in follicular fluid, and its granulosa cells produce more estradiol in vitro than cells from subordi nate follicles. Shortly after selection, dominant follicles have higher lev els of mRNAs for gonadotropin receptors and steroidogenic enzymes. it has b een hypothesized that granulosa cells of the selected follicle acquire LH r eceptors (LHr) to allow them to increase aromatization in response to LH, a s well as FSH. However, LH does not appear to stimulate estradiol productio n by bovine granulosa cells, and the role of LHr acquisition remains to be determined. Recent evidence suggests a key role for changes in the intrafol licular insulin-like growth factor (IGF) system in selection of the dominan t follicle. When follicular fluid was sampled in vivo before morphological selection, the lowest concentration of IGF binding protein-4 (IGFBP-4) was more predictive of future dominance than size or estradiol concentration. C onsistent with this finding, dominant follicles acquire an FSH-induced IGFB P-4 protease activity. Thus, a decrease in IGFBP-4, which would make more I GF available to interact with its receptors and synergize with FSH to promo te follicular growth and aromatization, appears to be a critical determinan t of follicular selection for dominance.