title: Biochemical and molecular effects of gestational and lactational coexposure to lead and cadmium on ovarian steroidogenesis are associated with oxidative stress in F1 generation rats.
abstract: 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.
authors.affiliation: Department of Biochemistry, Faculty of Science, The M. S. University of Baroda, Vadodara 390 002, Gujarat, India.
authors.forename: Prakash
authors.initials: P
authors.lastname: Pillai
authors.forename: Chirayu
authors.initials: C
authors.lastname: Pandya
authors.forename: Sharad
authors.initials: S
authors.lastname: Gupta
authors.forename: Sarita
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D015536:Down-Regulation; D005260:Female; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis*; D007774:Lactation; D007854:Lead / Q000633:toxicity*; D008297:Male; D018811:Maternal Exposure; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D012739:Gonadal Steroid Hormones; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D002104:Cadmium; D007854:Lead