Testicular toxicity and mechanisms of chlorotoluron compounds in the mouse

ABSTRACT Background: Previous studies have reported that chlorotoluron has adverse effects on male mice. Few studies, however, have investigated the mechanism of action of these herbicides. The effects of chlorotoluron and atrazine ingestion on male mouse reproductive function during the peripubertal period are reported here.

A total of 16 experimental groups and one control group were used in this study. Each experimental group was treated with chlorotoluron or atrazine alone or in combination in different doses. After mice were sacrificed, superoxide dismutase activity in blood was measured, weight ratios of testis to body were calculated, and testis tissues were examined by light and transmission electron microscopy.

The decreased weight ratio of mouse testis to body weight resulted in a reduction in the relative testis weight. Experiments on SOD enzyme activity in vivo showed that the synergistic effect of the two compounds was more notable at higher concentrations. Histological analyses of testes of animals treated with herbicides showed that the epithelium of seminiferous tubules was loosely arrayed and lacked order, spermatogenic cells were shed, and fewer layers formed. By electron microscopy it was noted that mitochondria in the seminiferous epithelium appeared vacuolated; nuclei were enlarged and irregular. In addition, the number of Sertoli cells was reduced, and part of the tight junction was destroyed. The results demonstrated that these herbicides induced degeneration and severe pathological changes in a dose-dependent manner. The toxic effects of chlorotoluron were more potent than those of atrazine when each was administrated alone. Moreover, when administered in combination, the two compounds had synergistic toxic effects.