Atrazine blocks ovulation via suppression of Lhr and Cyp19a1 mRNA and estradiol secretion in immature gonadotropin-treated rats

We investigated whether in vivo exposure to herbicide atrazine (ATR) exerts anovulatory effect by direct action in the ovary. Female rats were given ATR (50 mg/kg body weight) during equine chorionic gonadotropin (eCG) priming. Forty eight hours after eCG administration, the animals were injected with human CG (hCG) to induce ovulation. ATR blocked ovulation and prevented expression of epiregulin and progesterone receptor mRNA in hCG-treated animals. During eCG-induced follicular growth, ATR suppressed luteinizing hormone receptor (Lhr) and aromatase expression in granulosa cells and decreased estradiol (E-2) serum levels. ATR increased cytochrome p450 1b1 (Cyp1b1) mRNA expression after both in vivo and in vitro exposures. In vitro addition of beta-naphthoflavone, a known Cyp1b1 mRNA inductor, suppressed follicle-stimulating hormone-induced Lhr expression. Collectively, these data indicate that under in vivo conditions, ATR may act directly on granulosa cells by decreasing E-2 levels and Lhr mRNA, thus leading to inhibition of ovulation. (C) 2016 Elsevier Inc. All rights reserved.