Preventing Granulosa Cell Apoptosis Through the Action of a Single MicroRNA1

Abstract

The development and rupture of an ovulatory follicle is dependent upon the actions of the gonadotropins follicle-stimulating hormone and the midcycle surge of luteinizing hormone (LH), respectively. After rupture, the cellular remnants of the ovulatory follicle differentiate into steroid-secreting luteal cells. Continued survival of the granulosa cells following ovulation and their luteinization is critical for progesterone production and the ability to sustain pregnancy, and several studies [1–3] have documented a prosurvival effect from surge levels of LH on granulosa cells following its binding and signaling via LH/chorionic gonadotropin receptors (LHCGR). The balance between induction of proapoptotic and antiapoptotic pathways in granulosa cells residing within an ovulatory follicle, however, is complex and not well understood. Factors downstream of LH signaling that determine whether granulosa cell survival or apoptosis is favored have been discovered and investigated individually. For example, progesterone has an antiapoptotic effect on luteinized granulosa cells in most species studied, thereby promoting their continued survival and allowing development of the corpus luteum [4–7]. Other examples of individual factors that play a role in determining granulosa cell survival in the ovulatory follicle include pituitary adenylate cyclase-activating polypeptide (PACAP), epidermal growth factor-like (EGF) ligands, hyaluronan and proteoglycan link protein 1 (HAPLN1), as well as phosphatase and tensin homolog (PTEN) [8–11]. Each of these components regulates distinct pathways that in turn ultimately regulate the induction of apoptosis. A report by Carletti et al. [12] in this issue of Biology of Reproduction provides insight regarding a novel mechanism whereby granulosa cell survival is maintained in the ovulatory follicle after LHCGR signaling through the synthesis and action of a specific microRNA (miRNA).