HEAT SHOCK PROTEINS IN SERTOLI CELL TOXICITY

多种抑雄剂毒性的生化机制

The biochemical mechanism of toxicity of many agents that inhibit male fertility are largely unknown. Dibromochloropropane (DBCP), cadmium chloride (Cd) and methoxyethanol depress sperm counts. DBCP, Cd and MA (methoxyacetate, the toxic metabolite of methoxyethanol) alter biochemical endpoints of function when applied to primary cultures of Sertoli cells. Since Sertoli cells provide morphological and biochemical support for spermatogenesis in the mammalian testes, agents that inhibit Sertoli cell function would be expected to depress male fertility. Cd causes the synthesis and phosphorylation of two low molecular weight proteins by Sertoli cells that have been identified as heat shock proteins. This proposal examines the hypothesis that the induction of the heat shock response in testicular cells is a critical step in the mechanism of heat - and chemical-induced inhibition of spermatogenesis. The synthesis of the small heat shock proteins, their phosphorylation and the transcription of their mRNA will be determined and correlated with the biochemical alterations noted in rat Sertoli cell cultures exposed to DBCP, Cd and MA. In situ hybridization will be used to localize the site of synthesis of the small heat shock proteins in the testis of rats exposed to DBCP, MA and Cd. This will also allow the association of low molecular weight heat shock proteins when sites and stages of selective loss of germ cells.