title: Bisphenol A enhances kisspeptin neurons in anteroventral periventricular nucleus of female mice.
abstract: Bisphenol-A (BPA), an environmental estrogen, adversely affects female reproductive health. However, the underlying mechanisms remain largely unknown. We found that oral administration (p.o.) of BPA (20  μg/kg) to adult female mice at proestrus, but not at estrus or diestrus, significantly increased the levels of plasma E₂, LH and FSH, and Gnrh mRNA within 6  h. The administration of BPA at proestrus, but not at diestrus, could elevate the levels of Kiss1 mRNA and kisspeptin protein in anteroventral periventricular nucleus (AVPV) within 6  h. In contrast, the level of Kiss1 mRNA in arcuate nucleus (ARC) was hardly altered by BPA administration. In addition, at proestrus, a single injection (i.c.v.) of BPA dose-dependently enhanced the AVPV-kisspeptin expression within 6  h, this was sensitive to E₂ depletion by ovariectomy and an estrogen receptor α (ERα) antagonist. Similarly, the injection of BPA (i.c.v.) at proestrus could elevate the levels of plasma E₂, LH, and Gnrh mRNA within 6  h in a dose-dependent manner, which was blocked by antagonists of GPR54 or ERα. Injection of BPA (i.c.v.) at proestrus failed to alter the timing and peak concentration of LH-surge generation. In ovariectomized mice, the application of E₂ induced a dose-dependent increase in the AVPV-Kiss1 mRNA level, indicating 'E₂-induced positive feedback', which was enhanced by BPA injection (i.c.v.). The levels of Erα (Esr1) and Erβ (Esr2) mRNAs in AVPV and ARC did not differ significantly between vehicle-and BPA-treated groups. This study provides in vivo evidence that exposure of adult female mice to a low dose of BPA disrupts the hypothalamic-pituitary-gonadal reproductive endocrine system through enhancing AVPV-kisspeptin expression and release.
authors.affiliation: State Key Laboratory of Reproductive Medicine Department of Physiology, Nanjing Medical University, Hanzhong Road 140, Nanjing 210029, China MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Chang
authors.forename: Yinyang
authors.initials: Y
authors.lastname: Bai
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006066:Gonads / Q000187:drug effects / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D059648:Kisspeptins / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D020644:Midline Thalamic Nuclei / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D000074502:Receptors, Kisspeptin-1; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004958:Estradiol; D059648:Kisspeptins; D010636:Phenols; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; C492248:Kiss1r protein, mouse; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: bisphenol-A (BPA); estrogen (E2); estrogen receptor (ER); hypothalamic–pituitary–gonadal (HPG) axis; kisspeptin neurons