Few studies have characterized the molecular and biochemical mechanisms involved in ovarian steroidogenesis disruption by
heavy metals, such as lead and
cadmium coexposure, on F1 generation offspring. In this study, adult pregnant female rats were treated subcutaneously (0.05 mg/kg of
body weight per day) with
sodium acetate (control),
lead acetate, and
cadmium acetate separately and in combination throughout gestational and lactational period, and all animals from each of the experimental groups were sacrificed by
decapitation on postnatal day 56 for various assays. The activities of key steroidogenic
enzymes (17β-
hydroxysteroid dehydrogenase and 3β-
hydroxysteroid dehydrogenase) decreased in all the
metal-treated groups. But the most significant decrease in the activities was observed in the
cadmium-treated group, whereas the combined exposure group showed an intermediate effect. Serum
estradiol and
progesterone levels were also significantly altered in all the
metal-treated groups, with the
cadmium-exposed group showing maximum reductions as compared with the control group. The inhibitory effects of lead and
cadmium on ovarian
steroidogenic acute regulatory protein (StAR)
mRNA levels along with CYP11
mRNA levels were also observed. Ovarian
cholesterol content measured also showed significant depletion in all the
metal-treated groups, with the
cadmium-exposed group showing the maximum depletion. The activities of ovarian enzymatic
antioxidants, such as
superoxide dismutase,
catalase, and
glutathione peroxidase, were all significantly diminished along with significant depletion in nonenzymatic
antioxidants. Lipid peroxidation was elevated significantly in all the
metal-treated groups. In conclusion, lead and
cadmium inhibit ovarian steroidogenesis by downregulating StAR gene expression along with inhibiting activities of steroidogenic
enzymes and
antioxidant system.