title: Bisphenol A causes malformation of the head region in embryos of Xenopus laevis and decreases the expression of the ESR-1 gene mediated by Notch signaling.
abstract: Bisphenol A (BpA) is widely used in industry and dentistry. Its effects on the embryonic development of Xenopus laevis were investigated. Xenopus embryos at stage 10.5 were treated with BpA. Developmental abnormalities were observed at stage 35; malformation of the head region including eyes and scoliosis. The expression of several markers of embryonic development was investigated by reverse transcription-polymerase chain reaction (RT-PCR). The pan-neural marker SOX-2, the neural stem cell marker nrp-1, the mesodermal marker MyoD, and the endodermal marker sox17alpha, were used. Although the expression of marker genes was not changed by treatment with BpA, that of Pax-6, a key regulator of the morphogenesis of the eyes, was decreased by BpA. Pax-6 is a downstream factor of Notch signaling. So, the expression of a typical Notch-dependent factor, ESR-1, was investigated in the presence of BpA. The expression of ESR-1 was efficiently suppressed by BpA. In whole mount in situ hybridization (WISH), Pax-6 was expressed in the central nervous system and eyes. The expression was lost completely on treatment with BpA. The expression of ESR-1 in the central nervous system and eyes also disappeared with BpA treatment. Injection of the intracellular domain of Notch efficiently recovered ESR-1 expression in the presence of BpA although injection of a ligand for notch, Delta, did not. These results suggest that BpA decreased the expression of ESR-1 by disrupting the Notch signal.
authors.affiliation: Nanobiotechnology Research Center and Department of Bioscience, School of Science and Technology, Kwansei Gakuin University, Sanda, Japan. imaoka@ksc.kwansei.ac.jp
authors.forename: Susumu
authors.initials: S
authors.lastname: Imaoka
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Mori
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kinoshita
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D004625:Embryo, Nonmammalian / Q000187:drug effects; D005136:Eye Proteins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006257:Head / Q000002:abnormalities*; D018398:Homeodomain Proteins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism; D008675:Metamorphosis, Biological / Q000187:drug effects; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D010636:Phenols / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics; D013723:Teratogens / Q000494:pharmacology*; D029867:Xenopus Proteins / Q000235:genetics; D014982:Xenopus laevis / Q000002:abnormalities*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D005136:Eye Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D010636:Phenols; D012333:RNA, Messenger; D051880:Receptors, Notch; D012097:Repressor Proteins; D013723:Teratogens; D029867:Xenopus Proteins; C504431:Esr1 protein, Xenopus; C064045:delta protein; C006780:bisphenol A; D000098826:Bisphenol A Compounds