Natriuretic Peptide Precursor C Delays Meiotic Resumption and Sustains Gap Junction-Mediated Communication in Bovine Cumulus-Enclosed Oocytes1

Abstract

Oocyte in vitro maturation (IVM) has become a valuable technological tool for animal breeding and cloning and the treatment of human infertility because it does not require the administration of exogenous gonadotropin to obtain fertilizable oocytes. However, embryo development after IVM is lower compared to in vivo maturation, most likely because oocytes collected for IVM are heterogeneous with respect to their developmental competencies. Attempts to improve IVM outcome have relied upon either prematuration culture (PMC) or two-step maturation strategies in the hope of normalizing variations in developmental competence. Such culture systems invoke the pharmacological arrest of meiosis, in theory providing oocytes sufficient time to complete the acquisition of developmental competence after cumulus-enclosed oocytes isolation from the follicle. The present study was designed to test the efficiency of natriuretic peptide precursor C (NPPC) as a nonpharmacologic meiosis-arresting agent during IVM in a monoovulatory species. NPPC has been shown to maintain meiotic arrest in vivo and in vitro in mice and pigs; however, the use of this molecule for PMC has yet to have been explored. Toward this end, meiotic cell cycle reentry, gap-junction functionality, and chromatin configuration changes were investigated in bovine cumulus-enclosed oocytes cultured in the presence of NPPC. Moreover, oocyte developmental competence was investigated after IVM, in vitro fertilization, and embryo culture and compared to standard IVM-in vitro fertilization protocol without PMC. Our results suggest that NPPC can be used to delay meiotic resumption and increase the developmental competence of bovine oocytes when used in PMC protocols.

Natriuretic peptides stimulate oocyte meiotic resumption in bovine

“…In contrast to our results, Franciosi et al (2014) demonstrated that 100 nM of NPPC delayed oocyte meiosis resumption after 6 or 8 h of culture, maintaining communication via gap junctions in bovine COCs. However, as observed by Bilodeau-Goeseels (2007) for NPPA in bovine, we similarly demonstrated that none of the NPs (NPPA, NPPB and NPPC), individually or combined, inhibit the rate of meiosis resumption in bovine oocytes (supplementary data).…”

Oocyte maturation and quality: role of cyclic nucleotides

“…NPR2 stimulation by CNP increased cGMP intracellular concentrations in both CCs and the oocyte and maintained meiotic arrest (Zhang et al 2010). CNP has since been identified as an oocyte-meiosis-inhibiting peptide in a range of species such as mice (Zhang et al 2010), swine (Santiquet et al 2014), cattle (Franciosi et al 2014) and rats (Zhang et al 2015). The physical characteristics and mode of action of CNP suggest it is likely to be the oocyte maturation inhibitor (OMI) found in follicular fluid, as described several decades ago (Tsafriri et al 1976).…”

Regulation of Mammalian Oocyte Meiosis by Intercellular Communication Within the Ovarian Follicle

“…Application of CNP (10–100 nM) to cumulus-oocyte complexes from mice (66, 74), pigs (75, 76), cows (77), and domestic cats (78) inhibits meiotic resumption. CNP does not inhibit meiotic resumption in isolated oocytes (66, 75, 76) because oocytes do not express NPR2 (66).…”