Bisphenol-A (BPA) is an estrogenic chemical extensively used in industrial and household applications. The present study was conducted to investigate the effect of chronic exposure to BPA on the adult female neuroendocrine system. Herein, we found that expose of adult female mice to BPA (50 μg/kg) by oral gavage for 60 days (BPA mice) prolonged diestrus and decreased serum 17β-estradiol (E2) concentration by reducing the number of antral follicles and corpora luteum. In comparison with controls, the levels of serum luteinizing hormone (LH), follicle stimulating hormone (FSH), hypothalamic gonadotrophin releasing hormone (GnRH) and the expression of kisspeptin in anteroventral periventricular nucleus (AVPV) decreased in BPA mice, which could be reversed by injecting kisspeptin-10 (i.c.v.). Treatment with BPA or estrogen receptor α (ERα) antagonist MPP, but not ERβ antagonist PHTPP inhibited E2-induced AVPV-kisspeptin expression in ovariectomized mice. Use of ERα agonist PPT rather than ERβ agonist DPN enhanced AVPV-kisspepetin expression, which decreased after treatment with BPA. The amplitude of the proestrus LH surge decreased in mice exposed to BPA, but was recovered by administering kisspeptin-10. The present study provides in vivo evidence that chronic exposure to a low dose of BPA suppressed ERα-induced activation of AVPV-kisspeptin neurons, leading to prolonged diestrus and reduced ovulation in adult female mice.

双酚A（BPA）是一种雌激素化学物质，广泛用于工业和家庭应用。进行本研究以调查长期暴露于BPA对成年女性神经内分泌系统的影响。在这里，我们发现成年雌性小鼠经口管饲法暴露于BPA（50μg/ kg）60天（BPA小鼠）可延长二头肌，并通过减少肛门卵泡和黄体的数量降低血清17β-雌二醇（E2）的浓度。 。与对照组相比，BPA小鼠腹腔前室周围核（AVPV）的血清黄体生成激素（LH），卵泡刺激素（FSH），下丘脑促性腺激素释放激素（GnRH）和kisseptin表达降低。通过注射kisspeptin-10（icv）。用BPA或雌激素受体α（ERα）拮抗剂MPP治疗，但不使用ERβ拮抗剂PHTPP治疗可抑制去卵巢小鼠中E2诱导的AVPV-kisspeptin表达。使用ERα激动剂PPT而不是ERβ激动剂DPN可以增强AVPV-kisspepetin的表达，而BPA治疗后该表达降低。在暴露于BPA的小鼠中，发情期LH激增的幅度降低，但通过施用kisspeptin-10可以恢复。本研究提供体内证据表明，长期暴露于低剂量的BPA会抑制ERα诱导的AVPV-kisspeptin神经元活化，导致成年雌性小鼠二头肌延长和排卵减少。