A New Understanding on the Regulation of Oocyte Meiotic Prophase Arrest and Resumption

Abstract

In mammals, oocyte maturation must be remained precisely in synchrony with ovulation for normal female fertility. Signals from ovarian somatic cells prevent precocious resumption of meiosis until a surge of luteinizing hormone (LH) from the pituitary stimulates oocyte maturation and ovulation. Natriuretic peptide type C (NPPC) produced by mural granulosa cells stimulates the generation of cyclic guanosine 3′,5′-monophosphate (cGMP) by natriuretic peptide receptor 2 (NPR2) of cumulus cells. The cGMP then diffuses into oocytes and arrests meiotic progression by inhibiting oocyte-specific phosphodiesterase 3A (PDE3A) activity and cyclic adenosine 3′,5′-monophosphate (cAMP) hydrolysis. Intraoocyte cAMP is produced by G-protein-coupled receptor GPR3/12 activation of adenylyl cyclase endogenous to the oocyte. Oocyte itself also promotes cumulus cell expression of NPR2 and inosine monophosphate dehydrogenase (IMPDH) to elevate cGMP levels for meiotic arrest. Follicle-stimulating hormone (FSH), through estradiol (E2), enhances NPPC/NPR2 expression to ensure meiotic arrest during antral follicular development. LH-induced epidermal growth factor (EGF)-like growth factors decrease NPPC content and NPR2 activity, resulting in cGMP decrease and meiotic resumption. A better understanding of these signaling networks on the regulation of oocyte meiotic progress will provide new opportunities for the manipulation of follicular functions for contraception or the treatment of infertility.