MOUSE OOCYTE MATURATION IS AFFECTED BY LITHIUM VIA THE POLYPHOSPHOINOSITIDE METABOLISM AND THE MICROTUBULE NETWORK

The incubation of mechanically denuded mouse oocytes in medium contain ing LiCl delayed both germinal vesicle breakdown (GVBD) and polar body extrusion in a dose-dependent and reversible manner. When myo-inosito l alone was added to the culture medium, we observed that it accelerat ed GVBD and increased the rate of polar body extrusion, whereas, when combined with LiCl, the normal timing of GVBD was recovered. In the sa me way, when inositol trisphosphate (InsP(3)) was microinjected into t he ooplasma, we observed an important improvement of the rate of GVBD, as compared to control oocytes, and prevention of lithium inhibition. However, neither myo-inositol nor InsP(3) were able to rescue totally the oocytes from the negative effect of lithium on polar body extrusi on. Moreover, lithium induced some important changes in microtubule an d chromosome organizations. Before extrusion of the first polar body, the reduction of the spindle size or the appearance of short individua lized chromosomes dispersed around a large aster of microtubules were often observed, whereas, after polar body extrusion, the spindle appea red smaller and chromosomes were often trapped in the midbody. Thus li thium affects mouse oocyte maturation at two different levels: GVBD an d polar body extrusion. Whereas the former seems to be affected via po lyphosphoinositide turnover, the latter is InsP(3)-independent and see ms to be influenced negatively via underdevelopment of microtubular st ructures. (C) 1994 Wiley-Liss, Inc.