The role of the tumor suppressor p53 in spermatogenesis

Abstract

The p53 protein appeared to be involved in both spermatogonial cell proliferation and radiation response. During normal spermatogenesis in the mouse, spermatogonia do not express p53, as analyzed by immunohistochemistry. However, after a dose of 4 Gy of X-rays, a distinct p53 staining was present in spermatogonia, suggesting that, in contrast to other reports, p53 does have a role in spermatogonia. To determine the possible role of p53 in spermatogonia, histological analysis was performed 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 A 1 spermatogonia, indicating that the production of differentiating 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 process in these cells. Third, in the p53 knock out testis, the differentiating A 2 -B spermatogonia are more radioresistant compared to their wild-type controls, indicating that p53 is partly indispensable in the removal of lethally irradiated differentiating type spermatogonia. In accordance with our immunohistochemical data, Western analysis showed that levels of p53 are increased in total adult testis lysates after irradiation. These data show that p53 is important in the regulation of cell production during normal spermatogenesis either by regulation of cell proliferation or, more likely, by regulating the apoptotic process in spermatogonia. Furthermore, after irradiation, p53 is important in the removal of lethally damaged spermatogonia.

p63 null mutation protects mouse oocytes from radio-induced apoptosis

“…displayed strong cytoplasmic labelling. Testes from adult wild-type mice were used as a positive control as p53 expression has previously been reported in spermatogonia (Beumer et al 1998). We obtained a similar pattern of staining (Fig.…”

p53 deficiency does not affect mutation rate in the mouse germline

“…Over recent years, the p53 knockout (KO) mice have widely been used as a useful model for the analysis of the in vivo effects of p53 deficiency on genome stability in somatic cells. However, to date, very little is known about the effects of p53 deficiency on mutation rate in the germline, where this protein is fully functional (Beumer et al, 1998). Here, using highly variable expanded simple tandem repeat (ESTR) loci we report that spontaneous and radiationinduced mutation rates in the p53 KO mice do not differ from those in the isogenic wild-type strain.…”

Caspase-independent death of meiotic and postmeiotic cells overexpressing p53: calpain involvement

“…In adult testis, tumor suppressor p53 is involved in apoptosis of spermatogonia after a genotoxic stress. 2,3 Classically, p53 induces apoptosis mainly via the intrinsic, mitochondrial pathway, which involves the initiator caspase-2 and caspase-9, and the downstream executioner caspases (3/7 and 6). Caspases are cysteine proteases present as precursors, activated by dimerization or by proteolytic cleavage after cell death signal triggering.…”