Quantitative Changes in Rat Seminiferous Epithelium After Chronic Administration of Low Doses of Cadmium and Zinc: A Stereological Study

The present study deals with the stereological analysis of the changes in the seminiferous epithelium of rat testis, mediated either by cadmium alone or by cadmium plus zinc, chronically administered at low oral doses. Stereological estimates of both labeling indices of proliferative cell nuclear antigen and TUNEL-stained nuclei of spermatogonia, and of ubiquitin, ubiquitin carboxyl-terminal hydrolase L1, caspase-3, and metallothionein cytoplasmic immunoreactivities from seminiferous epithelium were performed in rats non-treated (controls), CdCl2-exposed animals, and CdCl2 plus ZnCl2 -treated rats. The following conclusions can be drawn: a) The intake of low, oral doses of cadmium chloride over a long period of time induces quantitative changes in apoptosis of the seminiferous epithelium of the rats, without noticeable morphologic or proliferative alterations. b) The increase of mono-ubiquitin levels mediated by cadmium is caused by over expression of ubiquitin carboxyl-terminal hydrolase L1. c) Zinc exposure was able to decrease ubiquitin carboxyl-terminal hydrolase L1 and ubiquitin, but not sufficiently to reverse the apoptotic rate of the spermatogonia at the control level. d) It seems that metallothionein is not induced by the cadmium treatment alone. However, the results indicate that either cadmium in combination with zinc or zinc itself induces this enzyme.