Zinc protection against cadmium-induced infertility in female rats. Effect of zinc and cadmium on the progesterone production of cultured granulosa cells.

Abstract

Adult female rats were treated subcutaneously (s.c.) with zinc chloride (ZnCl2, 10 or 20 mg kg-1 body weight, bw) four times during two ovarian cycles. The third injection was accompanied by cadmium chloride (CdCl2) administration sc (2.5, 5 and 10 mg kg-1 bw). The fourth zinc (Zn) treatment was followed by mating. ZnCl2 (20 mg kg-1) itself impaired fertility by 20%, while CdCl2 dose-dependently blocked the receptivity of female rats. In combination with 2.5 and 5 mg kg-1 CdCl2 the metal salts decreased fertility in an additive fashion, whereas at the highest CdCl2 dose (10 mg kg-1) a marked ameliorating effect of ZnCl2 (10 and 20 mg kg-1) on cadmium (Cd)-caused sterility was observed. In the pregnant animals apart from the higher Cd-induced blood progesterone levels and reduced body weight gain of dams, no significant treatment-related maternal and fetal effects could be observed. ZnCl2 (10 to 80 microM) and CdCl2 (10 to 80 microM) were added to the culture medium of ovarian granulosa cells. CdCl2 suppressed follicle-stimulating-hormone- (FSH-) and cAMP-stimulated progesterone accumulation. No protective effect of Zn against Cd-induced drop in progesterone production could be seen, while Zn by itself induced a significant increase in FSH-supported progesterone synthesis. In conclusion, while Zn protected against Cd-induced sterility in vivo, it failed to counteract the direct effect of Cd on steroid biosynthesis. The data indicate that Zn protection does not take place at the level of ovary. Moreover, Zn and Cd seem to affect FSH-stimulated progesterone production by different mechanisms.