Porcine natriuretic peptide type B (pNPPB) maintains mouse oocyte meiotic arrest via natriuretic peptide receptor 2 (NPR2) in cumulus cells

In mouse ovarian follicles, the oocyte is maintained in meiotic prophase arrest by natriuretic peptide type C (NPPC) acting via its cognate receptor, natriuretic peptide receptor 2 (NPR2). As there is a marked species difference in the receptor selectivity of the natriuretic peptide family, this study examined the functional effect of other natriuretic peptides, type A (NPPA) and type B (NPPB), acting via NPR2 on mouse-oocyte meiotic arrest. The results by quantitative, reverse-transcriptase PCR showed that Npr2 was the predominant natriuretic peptide receptor transcript, and that Npr1 and Npr3 mRNA levels were negligible in cumulus cells isolated from equine chorionic gonadotropin (eCG)-primed, immature female mice. While NPPA and NPPB from human and rat had no effect on oocyte maturation, porcine NPPB (pNPPB) maintained oocyte meiotic arrest in a dose-dependent manner. Furthermore, pNPPB-mediated meiotic arrest and cGMP production could be completely blocked by the NPR2 inhibitor sphingosine-1-phosphate (S1P). Neither the NPR1 antagonist anantin or Npr1 knockout had an effect on pNPPB-mediated meiotic arrest. Thus, pNPPB can functionally maintain mouse-oocyte meiotic arrest by the receptor NPR2 of cumulus cells. These findings demonstrate that pNPPB may be used as a probe to identify the essential amino acid sequences for activation of NPR2.