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p63 expression pattern in foetal and neonatal gonocytes after irradiation and role in the resulting apoptosis by using p63 knockout mice

Purpose: To investigate the role of p63, a member of the p53 family, in gonocyte apoptosis after radiation exposure. Materials and methods: Wild-type (WT) and p63 knock-out (KO) testes were exposed in vivo or in vitro to a 3 Gy dose of 137Cesium (137Cs) γ-rays at day 18.5 post-conception (p.c.). p63 whole expression was studied in neonatal testes by immunohistochemistry, whereas TAp63 and ΔNp63 isoforms were studied by Reverse-transcribed Polymerase Chain Reaction (RT-PCR). Gonocyte apoptosis was analysed by immunohistochemistry (cleaved caspase 3) and In Situ End labelling (ISEL). Results: Such foetal irradiation leads to a strong increase of gonocyte apoptosis in newborns. It also induces the up-regulation of the TAp63α isoform and the down-regulation of the ΔNp63α isoform. Moreover, in control p63KO testis, a significant increase in the number of gonocytes was associated with a strong reduction of their apoptosis compared with the control wild-type testis. Unexpectedly, after irradiation this increase of the number of apoptotic gonocytes was seen in p63KO testis, which was comparable to that in irradiated p63WT testis. Conclusion: We demonstrate that p63 is able to trigger gonocyte apoptosis in control testis but is not necessarily required in their radio-induced apoptosis.