p63 null mutation protects mouse oocytes from radio-induced apoptosis.
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.
Livera
Gabriel
G
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. gabriel.livera@cea.fr
Petre-Lazar
Béatrice
B
Guerquin
Marie-Justine
MJ
Trautmann
Emilie
E
Coffigny
Hervé
H
Habert
René
R
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western / Q000379:methods; D002452:Cell Count; D002467:Cell Nucleus / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000528:radiation effects*; D016158:Genes, p53; D049469:Meiotic Prophase I; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D009865:Oocytes / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D009924:Organ Culture Techniques; D010053:Ovary / Q000196:embryology* / Q000528:radiation effects*; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D014916:Whole-Body Irradiation
D004268:DNA-Binding Proteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins