title: Effect of fetal exposure to bisphenol A on brain mediated by X-chromosome inactivation.
abstract: Recent studies have reported that bisphenol A (BPA) influences brain development in fetal exposure to mice. The X-chromosome codes many neurodevelopment-related genes leading to abnormal development, such as mental retardation and intellectual deficiency. For females, most of expressions of X-linked genes are regulated by X-chromosome inactivation (XCI), which occurs during fetal period, and this mechanism is regulated by Xist and its antisense, Tsix. To clarify the possibility of X-mediated effect as a mechanism of neurodevelopmental disorders by BPA, pregnant ICR mice were orally administered 0.02 or 50 mg/kg of BPA on gestational days 6 and 15. Postnatally at days 2, 4 and weeks 3 and 7, mRNA expression of XCI-regulating factors (Xist and Tsix), X-linked neurodevelopment-related genes (Fmr1, Gdi1, Nlgn3, Pak3 and Ophn1), and sexual differentiation-related genes (ERα, ERβ and AR) were examined in cerebrums of female pups. Anogenital distance (AGD) and serum estradiol were also examined. In the 50 mg/kg exposed-group, reduced Xist, Fmr1, Gdi1, Nlgn3, and Pak3 and increased Tsix were observed simultaneously. Moderately reduced Xist, Gdi1, Nlgn3 and Pak3 were observed at 0.02 mg/kg BPA. ERα, ERβ and AR expression changes, shortened AGDs and reduced estradiol levels were observed in each exposure group. Fetal exposure to BPA changed expression of XCI-regulating factors and may alter the expression levels of X-linked neurodevelopment-related genes disrupting the XCI mechanism and function. This X-mediated effect is considered one of the mechanisms of various BPA-induced neurodevelopmental disorders.
authors.affiliation: School of Pharmaceutical Sciences, Ohu University, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kumamoto
authors.forename: Shigeru
authors.initials: S
authors.lastname: Oshio
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D001921:Brain / Q000002:abnormalities* / Q000196:embryology* / Q000254:growth & development; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects* / Q000235:genetics*; D018811:Maternal Exposure / Q000009:adverse effects*; D008431:Maternal-Fetal Exchange; D038901:X-Linked Intellectual Disability / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D055495:Neurogenesis / Q000187:drug effects* / Q000235:genetics*; D010636:Phenols / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000502:physiology*; D012733:Sex Differentiation / Q000235:genetics; D049951:X Chromosome Inactivation / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D062085:RNA, Long Noncoding; C465658:Tsix transcript, mouse; C077885:XIST non-coding RNA; C006780:bisphenol A; D000098826:Bisphenol A Compounds