Maternal exposure to environmentally relevant doses of bisphenol A causes reproductive dysfunction in F1 adult male rats: protective role of melatonin.

Abstract

This study investigated the protective effects of melatonin (MLT), a potent antioxidant, in male Wistar rats exposed to environmentally relevant doses of bisphenol A (BPA) in utero. Pregnant Wistar rats were randomly assigned into five groups. Group 1 (control) received 0.2 mL 1% dimethyl sulfoxide (DMSO)/99% canola oil as vehicle; group 2 received BPA at 25 μg/kg/day; group 3 received BPA at 250 μg/kg/day; group 4 received BPA at 25 μg/kg/day with concurrent MLT 1 mg/kg/day while group 5 received BPA at 250 μg/kg/day with concurrent MLT 1 mg/kg/day. Treatments were by gavage from gestational day (GD) 10-21. The BPA-treated rats showed dose-dependent significant reduction in body weight, gonosomatic index, sperm motility, livability and count. Also, BPA caused significant reduction in the levels of serum testosterone and luteinizing hormone while it caused significant increases in the levels of follicle stimulating hormone as well as estradiol. Furthermore, BPA induced testicular oxidative stress including significant decreases in the activities of testicular SOD, GSH and GPx as well as GST, increasing the levels of testicular MDA and H2O2. It further induced interstitial necrosis and germinal cell degeneration in the testis with a subsequent diminution of the tubular and luminal diameter. However, co-treatment with MLT offered protection against testicular damage induced by BPA. Melatonin is likely to protect against alterations of the male reproductive system caused by BPA through a direct action on the mechanism of anti-oxidants as well as through the inhibition of necrosis.