Pre-ovulatory events in the rhesus monkey follicle during ovulation induction

Abstract

Pituitary gonadotrophins, notably LH, and ovarian steroids, such as progesterone, play essential roles in the events leading to ovulation of the mature follicle and development of the subsequent corpus luteum. Rhesus monkeys (Macaca mulatta) undergoing controlled ovarian stimulation cycles comparable to those in clinical IVF/assisted reproduction treatment protocols provide a non-human primate model for studying peri-ovulatory events. The ability to manipulate the intrafollicular steroid milieu, via oral administration of a steroid synthesis inhibitor, with or without steroid replacement, allows one to distinguish between gonadotrophin-initiated, steroid-dependent versus steroid-independent processes. The length of the peri-ovulatory interval (onset of the LH surge to follicle rupture) is long (36-40 h) in primates and can be considered in terms of early (< or = 12 h) versus later (> or = 24 h) events. Granulosa cells lose their proliferative activity and differentiate into progesterone-secreting cells during the early peri-ovulatory interval. The rapid increase in progesterone synthetic capacity and expression of progesterone receptors suggests that this steroid has early actions, e.g. in controlling cell cycle machinery or differentiation. However, it is not until later that morphological luteinization is evident. By this stage, progesterone may serve as a potent anti-apoptotic factor and regulator of tissue remodelling through control of protease expression and activity, angiogenesis, or other events. Application of modern techniques to study LH- and progesterone-responsive gene expression will further unravel ovulatory and luteinization processes in specific compartments of the primate follicle.