Doxorubicin-induced apoptosis in germinal vesicle (GV) oocytes

Ovarian failure is a-known side-effect observed in women treated for cancer Doxorubicin (DXR) was found to be detrimental to MII mouse oocytes We aimed at characterizing the effect of DXR on germinal vesicle (GV) oocytes that comprise the majority of oocytes within ovaries encountering chemotherapy Mouse follicles and oocytes were exposed to DXR in vitro DXR localization and its possible cellular targets were examined by fluorescence confocal microscopy We demonstrated that DXR crosses the blood-follicle barrier and accumulates in oocytes and granulosa cells The mechanism of DXR-induced apoptosis involves chromosomal disintegration activation of the mitochondria followed by activation of PERK and caspase-12 and inactivation of PARP The follicular GV oocytes were more vulnerable to the toxic effect of DXR than ovulated MII oocytes We suggest that DXR elicits apoptotic signal within GV oocytes that involves activation of the mitochondria induction of ER-stress and a possible Increase in intracellular calcium (C) 2010 Elsevier Inc All rights reserved