p63 expression pattern in foetal and neonatal gonocytes after irradiation and role in the resulting apoptosis by using p63 knockout mice.
OBJECTIVE
To investigate the role of p63, a member of the p53 family, in gonocyte apoptosis after radiation exposure.


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) gamma-rays at day 18.5 post-conception (p.c.). p63 whole expression was studied in neonatal testes by immunohistochemistry, whereas TAp63 and DeltaNp63 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 TAp63alpha isoform and the down-regulation of the DeltaNp63alpha 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.


CONCLUSIONS
We demonstrate that p63 is able to trigger gonocyte apoptosis in control testis but is not necessarily required in their radio-induced apoptosis.
Petre-Lazar
B
B
CEA, Centre de Fontenay-aux-Roses, Laboratory of Differentiation and Radiobiology of Gonads, DSV/DRR/SEGG, Fontenay-aux-Roses, France.
Moreno
S G
SG
Livera
G
G
Duquenne
C
C
Habert
R
R
Coffigny
H
H
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D005333:Fetus / Q000528:radiation effects*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000032:analysis / Q000502:physiology*; D011836:Radiation Tolerance; D013094:Spermatozoa / Q000473:pathology / Q000528:radiation effects*; D013737:Testis / Q000737:chemistry / Q000528:radiation effects; D015534:Trans-Activators / Q000032:analysis / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D010750:Phosphoproteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse; D016159:Tumor Suppressor Protein p53