Hum. Reprod. Advance Access published online on December 16, 2008
Human Reproduction, doi:10.1093/humrep/den410
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Sex-specific differences in fetal germ cell apoptosis induced by ionizing radiation
1 CEA, DSV/DRR/SEGG/LDRG, Laboratory of Differentiation and Radiobiology of the Gonads, Unit of Gametogenesis and Genotoxicity, F-92265 Fontenay aux Roses, France 2 Univ. Paris 7—Denis Diderot, UFR of Biology, UMR-S 566, F-92265 Fontenay aux Roses, France 3 INSERM, U566, F-92265 Fontenay aux Roses, France 4 Institute of Experimental Morphology and Anthropology, Bulgarian Academy of Sciences, Sofia, Bulgaria 5 Univ Paris-Sud, Clamart F-92140, France 6 AP-HP, Service de Gynécologie-Obstétrique et Médecine de la Reproduction, Hôpital Antoine Béclère, Clamart F-92141, France 7 INSERM, U782, Clamart F-92140, France
8 Correspondence address. Unit of Gametogenesis and Genotoxicity, CEA, Université Paris 7, INSERM U566, CEA/DSV/DRR/SEGG/LDRG, Route du Panorama-BP6, 92265 Fontenay aux Roses Cedex, France. Tel: +33-1-46-54-99-36; Fax: +33-1-46-54-99-06; E-mail: gabriel.livera{at}cea.fr
BACKGROUND: We have previously shown that male human fetal germ cells are highly radiosensitive and that their death depends on p53 activation. Male germ cell apoptosis was initiated with doses as low as 0.1 Gy and was prevented by pifithrin 
, a p53 inhibitor. In this study, we investigated the radiosensitivity of early female and male fetal proliferating germ cells.
METHODS AND RESULTS: Both male and female fetal germ cells displayed a similar number of 
H2AX foci in response to ionizing radiation (IR). In organ culture of human fetal ovaries, the germ cells underwent apoptosis only when exposed to high doses of IR (1.5 Gy and above). Accumulation of p53 was detected in irradiated male human fetal germ cells but not in female ones. Inhibition of p53 with pifithrin did not affect oogonia apoptosis following irradiation. IR induced apoptosis similarly in mouse fetal ovaries in organ culture and in vivo during oogonial proliferation. Germ cell survival in testes from p53 knockout or p63 knockout mice exposed to IR was better than wild-type, whereas female germ cell survival was unaffected by p53 or p63 knockout.
CONCLUSIONS: These findings show that pre-meiotic male and female fetal germ cells behave differently in response to a genotoxic stress—irradiation—with oogonia being less sensitive and undergoing p53-independent apoptosis.
Key words: gonocyte/oogonia/ionizing radiation/apoptosis/p53
Submitted on April 22, 2008; resubmitted on October 10, 2008; accepted on October 17, 2008.