PKCδ and θ possibly mediate FSH-induced mouse oocyte maturation via NOX-ROS-TACE cascade signaling pathway.

Abstract

In mammals, gonadotropins stimulate oocyte maturation via the epidermal growth factor (EGF) network, and the protein kinase C (PKC) signaling pathway mediates this process. Tumor necrosis factor-α converting enzyme (TACE) is an important protein responding to PKC activation. However, the detailed signaling cascade between PKC and TACE in follicle-stimulating hormone (FSH)-induced oocyte maturation in vitro remains unclear. In this study, we found that rottlerin (mallotoxin, MTX), the inhibitor of PKC δ and θ, blocked FSH-induced maturation of mouse cumulus-oocyte complexes (COCs) in vitro. We further clarified the relationship between two molecules downstream of PKC δ and θ and TACE in COCs: nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and its products, reactive oxygen species (ROS). We proved that the respective inhibitors of NOX, ROS and TACE could block FSH-stimulated oocyte maturation dose-dependently, but these inhibitory effects could be reversed partially by amphiregulin (Areg), an EGF family member. Notably, inhibition of PKC δ and θ prevented FSH-induced translocation of two cytosolic components of NOX, p47phox and p67phox, to the plasma membrane in cumulus cells. Moreover, FSH-induced TACE activity in cumulus cells was decreased markedly by inhibition of NOX and ROS. In conclusion, PKC δ and θ possibly mediate FSH-induced meiotic resumption in mouse COCs via NOX-ROS-TACE signaling pathway.