Lithium stimulates the first meiotic division in mouse oocytes

Cumulus enclosed oocytes, cumulus enclosed oocytes denuded of their cumulus and cumulus free oocytes from 21 day old unstimulated mice were cultured for 18 hours in control medium supplemented with lithium chloride, dbcAMP and forskolin at various concentrations. In control medium 66% of the cumulus enclosed oocytes, 93% of the denuded oocytes, and 94% of the cumulus free oocytes resumed meiosis (germinal vesicle breakdown), whereas the levels of polar body formation were 27%, 12% and 39%, respectively. In the presence of lithium significantly more cumulus enclosed oocytes and cumulus free oocytes resumed meiosis and formed a polar body, whereas lithium had no effect on the denuded oocytes. Forskolin and dbcAMP stimulated resumption of meiosis and cumulus expansion in the cumulus enclosed oocytes and inhibited resumption of meiosis in the cumulus free oocytes. Lithium more or less eliminated this inhibitory effect of both forskolin and dbcAMP in the cumulus free oocytes. The results indicate (i) that activation of the cAMP second messenger path in the cumulus cells induces them to synthesize a meiosis inducing substance(s) which stimulates the oocyte to resume meiosis, and (ii) that other second messenger systems than the cAMP pathway, e.g. the phosphatidylinositol cycle, are involved in resumption of meiosis and polar body formation. We conclude that lithium enhances the capability of mouse oocytes for resumption of meiosis and polar body formation.