Lead cations affect the control of both meiosis arrest and meiosis resumption of the mouse oocyte in vitro at least via the PKC pathway

The aim of this study was to determine in vitro whether lead has a direct cytotoxic effect on the female gamete or through its surrounding somatic cells. We had previously demonstrated that it partly accumulates in the mouse ovary and induces follicle and oocyte apoptosis. The data reported here demonstrate for the first time that low levels of Pb(NO3)2 (≤ 10 pM) affect oocyte meiosis in vitro. On the one hand, in condition similar to the in vivo one, i.e. in hypoxanthine (HX)-maintained meiotic arrest, Pb(NO3)2 was able to significantly release the oocytes from this arrest. On the other hand, when meiosis occurred spontaneously in vitro, Pb(NO3)2 inhibits meiosis. Whereas PMA, an agonist of PKC was able to prevent the first lead effect, calphostin C, an antagonist, was able to significantly prevent lead inhibition of spontaneous GVBD. And, similarly to Pb 2+, the inhibition of PKC by calphostin C prevented HX to maintain the meiotic arrest whereas its activation by PMA inhibited spontaneous GVBD. No significant differences in the effects of Pb(NO3)2 on the oocytes were observed whatever the cumulus cells were present or absent. Moreover, lead did not seem to affect the metaphase plate formation. We concluded that Pb 2+ may disturb the control of oocyte meiosis at least in part through its ability to interfere with the PKC pathway in taking place of Ca 2+ ions.