Brain Natriuretic Peptide and C‐Type Natriuretic Peptide Maintain Porcine Oocyte Meiotic Arrest

Abstract

Recent studies have shown that C-type natriuretic peptide (CNP) serves as a key control system during mouse oocyte maturation. We used pig models (in vitro and in vivo) to explore the role played by the natriuretic peptide family in porcine oocyte maturation. We reported the expression and location of natriuretic peptide system in different stages of porcine antral follicles. Atrial natriuretic peptide (ANP) and CNP were expressed primarily in granulosa cells, whereas brain natriuretic peptide (BNP) and natriuretic peptide receptor-B (NPRB) receptor were expressed in granulosa cells (both cumulus and mural granulosa cells) and thecal internal cells, and the natriuretic peptide receptor-A (NPRA) receptor predominantly in thecal cells. Upon in vitro culture, BNP and CNP maintained meiotic arrest of oocytes associated with cumulus cells. The expression levels of BNP, CNP, and the NPRB receptor increased upon treatment of prepubertal gilts with pregnant mare's serum gonadotropin and decreased upon subsequent human chorionic gonadotropin injection. Such dynamic changes in the expression of natriuretic peptides and their receptor paralleled the proportions of oocytes exhibiting nuclear maturation in vivo. These data indicated that BNP and CNP co-contributed to maintaining porcine meiotic arrest under physiological condition and lutenizing hormone (LH) relieved this inhibitory effect by decreasing the expression levels of BNP and CNP in vivo. Our present work, combined with previous data, improved the understanding of the oocyte meiotic arrest mechanisms and further revealed that natriuretic peptides serve as oocyte maturation inhibitor (OMI) to inhibit oocyte maturation in mammals.

Natriuretic peptides stimulate oocyte meiotic resumption in bovine

“…It appears that this is the first study showing that these three peptides have similar functions in same species. However, this contrasts with the effects of NPPA that have been reported in rats (Tornell et al, 1990), and of NPPC in mice (Zhang et al, 2010), as well as the effects of NPPB and NPPC that have been recently reported in pigs (Hiradate et al, 2013;Zhang et al, 2015), in which these peptides are essential for maintaining oocyte meiotic arrest. Initially, we observed that mRNA for NPPA, NPPC and their receptors (NPR-1, NPR-2 and NPR-3) were present in cumulus cells, and that in the bovine oocyte only mRNA for NPR-2 was present (Fig.…”

“…The natriuretic peptides (NPs) system consists of three endogenous peptides with high homology: NP precursor type-A (NPPA), type-B (NPPB) and type-C (NPPC), as well as three receptors (NPR-1, -2 and -3) that are located on NPPC is essential to block meiosis in mice (Zhang et al, 2010;Tsuji et al, 2012) and pigs (Hiradate et al, 2013;Zhang et al, 2015). Loss-of-function mutations in either NPPC or NPR-2 result in precocious resumption of meiosis in oocytes that are enclosed within antral follicles (Zhang et al, 2010;Tsuji et al, 2012;Geister et al, 2013).…”

Dephosphorylation and inactivation of NPR2 guanylyl cyclase in granulosa cells contributes to the LH-induced decrease in cGMP that causes resumption of meiosis in rat oocytes

“…LH acts by lowering the levels of cGMP in the granulosa cells, thus reducing cGMP in the oocyte. Although this regulatory system is best understood in mice (Norris et al, 2009;Vaccari et al, 2009;Zhang et al, 2010;Kawamura et al, 2011;Tsuji et al, 2012;Geister et al, 2013), there is evidence that similar mechanisms operate in other mammals (Törnell et al, 1991;Peng et al, 2013;Hiradate et al, 2014;Zhang et al, 2014), including women (Kawamura et al, 2011;Liu et al, 2014). The LH-induced resumption of the meiotic cell cycle leads into a series of events by which the oocyte matures to become a fertilizable egg (Conti et al, 2012;Clift and Schuh, 2013;Holt et al, 2013;Mehlmann, 2013;Hunzicker-Dunn and Mayo, 2014).…”

“…LH signaling is known to decrease the amount of CNP in rat and mouse ovaries (Jankowski et al, 1997;Kawamura et al, 2011;Liu et al, 2014) and in human and porcine follicular fluid (Kawamura et al, 2011;Zhang et al, 2014); the decrease in the levels of CNP is associated with a decrease in Nppc mRNA (Kawamura et al, 2011;Tsuji et al, 2012;Liu et al, 2014). However, in the mouse ovary, where the kinetics are best characterized, the CNP decrease is first detected at 2 h Liu et al, 2014), whereas the decrease in cGMP is detected at 15 to 20 min (Norris et al, 2010;Liu et al, 2014).…”

ADAM10–Notch signaling governs the recruitment of ovarian pregranulosa cells and controls folliculogenesis in mice

“…In situ hybridization was performed as described previously (Zhang et al, 2015). Briefly, ovaries with ovarian capsules were dissected from mice and were embedded in optimal cutting temperature (OCT) compound and frozen in liquid nitrogen until analysis.…”