p63 null mutation protects mouse oocytes from radio-induced apoptosis
p63 null mutation protects mouse oocytes from radio-induced apoptosis
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DOI：
10.1530/rep-07-0054
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发表时间：
2008-01-01
期刊：
影响因子：
3.8
通讯作者：
Habert, Rene
中科院分区：
文献类型：
--
作者：
Livera, Gabriel;Petre-Lazar, Beatrice;Habert, Rene
哺乳动物的雌性生育力由原始卵泡池决定，低剂量辐射会导致卵巢中原始卵泡的大量丧失。我们研究了p53及其同源物，p63和p73，在正常和辐射的新生儿卵巢的表达。p63是p53家族中唯一在卵母细胞核中检测到的成员。在早期胎儿卵巢中未检测到p63转录本或蛋白。在小鼠和人类中，p63的产生开始于粗线期晚期的卵母细胞，并在双线期卵母细胞中达到峰值。p63的产生与减数分裂DNA双链断裂修复有关。卵巢中仅存在反式激活（TA）亚型，TAp 63 α在mRNA和蛋白质水平上是迄今为止最丰富的。p63基因完全缺失突变不影响正常卵巢发育。辐射迅速触发p63磷酸化。p63无效突变阻止了caspase-9和caspase-3的切割以及电离辐射诱导的卵泡丢失。因此，我们的研究结果表明，辐射诱导的原始卵泡池耗尽的结果从静止卵母细胞中的p63的激活。
Female fertility in mammals is determined by the pool of primordial follicles and low doses of radiation induce a major loss of primordial follicles in the ovary. We investigated the expression of p53 and its homologues, p63 and p73, in the normal and irradiated neonatal ovary. p63 was the only member of the p53 family detected in oocyte nucleus. No p63 transcripts or protein were detected in the early foetal ovary. p63 production began in late pachytene-stage oocytes and peaked in diplotene oocytes in mice and humans. The production of p63 was correlated with meiotic DNA double-strand break repair. Only transactivation (TA) isoforms were present in the ovary, with TAp63 alpha by far the most abundant in terms of mRNA and protein levels. Complete p63 null mutation did not affect normal ovary development. Irradiation rapidly triggered p63 phosphorylation. p63 null mutation prevented the cleavage of caspases-9 and -3 and the follicle loss induced by ionising radiation. Thus, our results evidence that irradiation-induced depletion of the primordial follicle pool results from the activation of p63 in quiescent oocytes.