High sensitivity of rat foetal germ cells to low dose-rate irradiation

Purpose: To investigate the response of germ and Sertoli cells to gamma -ir radiation at two distinct periods of testicular development in rat foetuses . Materials and methods: Pregnant rats were exposed to Co-60 gamma -rays at d ays 15, 19 or 21 post-coitum (p.c.), at doses ranging from 0.1 to 1.5 Gy, a nd at different dose-rates. Testicular weight, seminiferous tubule conditio n 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 e xpression was studied by immunohistochemistry Results: At high dose-rates (greater than or equal to3.3 Gy min(-1)), 1.5 G y 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 apoptosi s. Apoptotic cells were strongly clustered. The remaining germ cells divide d and differentiated normally leading to a majority of normal tubules in th e adult testis. However, at low dose-rate (0.6 mGy min(-1)), much greater d epopulation of the seminiferous tubules occurred. When irradiation was give n 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 1 5 p.c. Their proliferation became higher in prepubescent testis compared wi th controls, when irradiation occurred at day 19 p.c. Conclusion: The position of gonocytes in the cell cycle at the time of irra diation 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 t he syncitial organization of germ cells, favouring their cell synchronisati on or the transmission of death signalling when they are in a radiosensitiv e period.