Livera Gabriel, Petre-Lazar Béatrice, Guerquin Marie-Justine, Trautmann Emilie, Coffigny Hervé, Habert René
CEA, DSV/DRR/SEGG/LDRG, Unit of Gametogenesis and Genotoxicity, Laboratory of Differentiation and Radiobiology of the Gonads, F-92265 Fontenay aux Roses Cedex, France.
Reproduction. 2008 Jan;135(1):3-12. doi: 10.1530/REP-07-0054.
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.
哺乳动物的雌性生育能力由原始卵泡库决定，低剂量辐射会导致卵巢中原始卵泡大量减少。我们研究了p53及其同源物p63和p73在正常和受辐射新生卵巢中的表达。p63是在卵母细胞核中检测到的p53家族的唯一成员。在胎儿早期卵巢中未检测到p63转录本或蛋白质。p63的产生始于减数分裂粗线期晚期卵母细胞，并在小鼠和人类的双线期卵母细胞中达到峰值。p63的产生与减数分裂DNA双链断裂修复相关。卵巢中仅存在反式激活（TA）亚型，就mRNA和蛋白质水平而言，TAp63α最为丰富。p63完全缺失突变并不影响正常卵巢发育。辐射迅速触发p63磷酸化。p63缺失突变可防止半胱天冬酶-9和-3的裂解以及电离辐射诱导的卵泡丢失。因此，我们的结果证明，辐射诱导的原始卵泡库耗竭是由静止卵母细胞中p63的激活所致。
