THE ROLE OF THE TUMOR-SUPPRESSOR P53 IN SPERMATOGENESIS

The p53 protein appeared to be involved in both spermatogonial cell pr oliferation and radiation response, During normal spermatogenesis in t he mouse, spermatogonia do not express p53, as analyzed by immunohisto chemistry. However, after a dose of 4 Gy of X-rays, a distinct p53 sta ining was present in spermatogonia, suggesting that, in contrast to ot her reports, p53 does have a role in spermatogonia, To determine the p ossible role of p53 in spermatogonia, histological analysis was perfor med in testes of both p53 knock out C57BL/6 and FvB mice, The results indicate that p53 is an important factor in normal spermatogonial cell production as well as in the regulation of apoptosis after DNA damage . First, p53 knock out mouse testes contained about 50% higher numbers of Al spermatogonia, indicating that the production of differentiatin g type spermatogonia by the undifferentiated spermatogonia is enhanced in these mice, Second, 10 days after a dose of 5 Gy of X-rays, in the p53 knock out testes, increased numbers of giant sized spermatogonial stem cells were found, indicating disturbance of the apoptotic proces s in these cells, Third, in the p53 knock out testis, the differentiat ing A(2)-B spermatogonia are more radioresistant compared to their wil d-type controls, indicating that p53 is partly indispensable in the re moval of lethally irradiated differentiating type spermatogonia, In ac cordance with our immunohistochemical data. Western analysis showed th at levels of p53 are increased in total adult testis lysates after irr adiation. These data show that p53 is important in the regulation of c ell production during normal spermatogenesis either by regulation of c ell proliferation or, more likely, by regulating the apoptotic process in spermatogonia. Furthermore, after irradiation, p53 is important in the removal of lethally damaged spermatogonia.