TEMPERATURE-MEDIATED GERM-CELL LOSS IN THE TESTIS IS ASSOCIATED WITH ALTERED EXPRESSION OF THE CELL-CYCLE REGULATOR P53

The dependence of spermatogenesis on the relatively cool environment o f the scrotum is well known, and recent work has shown that germ cells undergo apoptosis upon exposure to abdominal temperature. p53 is a po tent inducer of apoptosis and regulator of cell growth, and is found i n high concentrations in the testis. The purpose of this study was to determine whether exposure of the testes to suprascrotal temperature w as associated with alterations in testicular p53 expression. Male adul t CD-1 mice were rendered unilaterally cryptorchid by surgically fixin g one testis to the anterior abdominal wall while leaving the contrala teral tests in the scrotum to serve as the euthermic control. p53 expr ession was evaluated in the cytoplasmic, soluble nuclear, and insolubl e fractions by Western blot analysis with the monoclonal p53 antibody pAb240. The weights of the scrotal testes were unchanged over the 15 d ay study period. The weights of the cryptorchid testes remained stable for 7 days and then decreased by approximately 40% over the next two days. Histological evidence of germ cell loss was evident only after d ay 7. Altered expression of p53 protein in the cryptorchid testis was noted beginning on day 7, and consisted of the expression of a new 47 kD isoform of p53 in the cytosolic form and a 30 kD isoform in the sol uble nuclear fraction. Scrotal testes showed no changes at any time po int. These results demonstrate altered expression of the regulatory pr otein p53 beginning 1-2 days prior to the onset of germ cell loss foll owing experimental unilateral cryptorchidism. Given the known function of p53 as an inducer of apoptotic cell death, these observations sugg est a significant role for p53 in temperature-mediated germ cell loss.