High sensitivity of rat foetal germ cells to low dose-rate irradiation.
OBJECTIVE
To investigate the response of germ and Sertoli cells to gamma-irradiation at two distinct periods of testicular development in rat foetuses.


METHODS
Pregnant rats were exposed to 60Co gamma-rays at days 15, 19 or 21 post-coitum (p.c.), at doses ranging from 0.1 to 1.5Gy, and at different dose-rates. Testicular weight, seminiferous tubule condition and the number of germ and Sertoli cells were measured at early and late times after irradiation. Apoptosis was studied by the ISEL method and p53 expression was studied by immunohistochemistry.


RESULTS
At high dose-rates (> or = 3.3 Gy min(-1)), 1.5 Gy radiation at day 15 p.c. had a short-term effect on germ cell survival. A large proportion of these cells rapidly underwent p53-independent apoptosis. Apoptotic cells were strongly clustered. The remaining germ cells divided and differentiated normally leading to a majority of normal tubules in the adult testis. However, at low dose-rate (0.6mGy min(-1)), much greater depopulation of the seminiferous tubules occurred. When irradiation was given at day 19 p.c., the same dose had a delayed effect on germ cells, leading to sterility. Sertoli cells had a normal survival for irradiation at day 15 p.c. Their proliferation became higher in prepubescent testis compared with controls, when irradiation occurred at day 19 p.c.


CONCLUSIONS
The position of gonocytes in the cell cycle at the time of irradiation seems to be a determining parameter for inducing gonocyte apoptosis. The strong effect of irradiation on germ cells at very low dose-rate and the appearance of clusters of apoptotic gonocytes may be a consequence of the syncitial organization of germ cells, favouring their cell synchronisation or the transmission of death signalling when they are in a radiosensitive period.
Moreno
S G
SG
Department de Radiobiologie et Radiopathologie, DSV/LRCG/CEA, Fontenay-aux-Roses, France.
Dutrillaux
B
B
Coffigny
H
H
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002452:Cell Count; D005260:Female; D005333:Fetus / Q000528:radiation effects*; D005640:Follicle Stimulating Hormone / Q000097:blood; D005854:Germ Cells / Q000528:radiation effects*; D008297:Male; D011247:Pregnancy; D011829:Radiation Dosage; D011836:Radiation Tolerance; D051381:Rats; D017207:Rats, Sprague-Dawley; D012671:Seminiferous Tubules / Q000528:radiation effects; D012708:Sertoli Cells / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D016159:Tumor Suppressor Protein p53; D005640:Follicle Stimulating Hormone