Doxorubicin-induced apoptosis in germinal vesicle (GV) oocytes
Doxorubicin-induced apoptosis in germinal vesicle (GV) oocytes
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DOI：
10.1016/j.reprotox.2010.07.003
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发表时间：
2010-12-01
影响因子：
3.3
通讯作者：
Shalgi, Ruth
中科院分区：
文献类型：
--
作者：
Bar-Joseph, Hadas;Ben-Aharon, Irit;Shalgi, Ruth
卵巢衰竭是一种已知的副作用。阿霉素(DXR)被发现对MII小鼠卵母细胞是有害的。我们研究了DXR对卵巢内大多数卵母细胞的生发泡(GV)卵母细胞的影响。体外用DXR对小鼠卵泡和卵母细胞进行DXR定位，并用荧光共聚焦显微镜观察其可能的细胞靶点。DXR跨越血卵泡屏障，在卵母细胞和颗粒细胞中蓄积。DXR诱导细胞凋亡的机制包括线粒体解体、perk和caspase-12的激活以及PARP-12的失活。滤泡型GV卵母细胞比排卵的MII卵母细胞更容易受到DXR的毒性作用。我们认为DXR在GV卵母细胞内引发了凋亡信号，包括激活线粒体，诱导内质网应激，以及可能增加细胞内钙(C)2010爱思唯尔公司版权所有
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