Title: | Gestational exposure to bisphenol a produces transgenerational changes in behaviors and gene expression |
Author(s): | Wolstenholme JT; Edwards M; Shetty SR; Gatewood JD; Taylor JA; Rissman EF; Connelly JJ; |
Address: | "Department of Biochemistry and Molecular Genetics, University of Virginia, P.O. Box 800733, Charlottesville, Virginia 22908, USA" |
ISSN/ISBN: | 1945-7170 (Electronic) 0013-7227 (Print) 0013-7227 (Linking) |
Abstract: | "Bisphenol A (BPA) is a plasticizer and an endocrine-disrupting chemical. It is present in a variety of products used daily including food containers, paper, and dental sealants and is now widely detected in human urine and blood. Exposure to BPA during development may affect brain organization and behavior, perhaps as a consequence of its actions as a steroid hormone agonist/antagonist and/or an epigenetic modifier. Here we show that BPA produces transgenerational alterations in genes and behavior. Female mice received phytoestrogen-free chow with or without BPA before mating and throughout gestation. Plasma levels of BPA in supplemented dams were in a range similar to those measured in humans. Juveniles in the first generation exposed to BPA in utero displayed fewer social interactions as compared with control mice, whereas in later generations (F(2) and F(4)), the effect of BPA was to increase these social interactions. Brains from embryos (embryonic d 18.5) exposed to BPA had lower gene transcript levels for several estrogen receptors, oxytocin, and vasopressin as compared with controls; decreased vasopressin mRNA persisted into the F(4) generation, at which time oxytocin was also reduced but only in males. Thus, exposure to a low dose of BPA, only during gestation, has immediate and long-lasting, transgenerational effects on mRNA in brain and social behaviors. Heritable effects of an endocrine-disrupting chemical have implications for complex neurological diseases and highlight the importance of considering gene-environment interactions in the etiology of complex disease" |
Keywords: | "Animals Benzhydryl Compounds Endocrine Disruptors/*toxicity Female Gene Expression/drug effects Male Mice Mice, Inbred C57BL Oligonucleotide Array Sequence Analysis Phenols/*toxicity Pregnancy Prenatal Exposure Delayed Effects Real-Time Polymerase Chain R;" |
Notes: | "MedlineWolstenholme, Jennifer T Edwards, Michelle Shetty, Savera R J Gatewood, Jessica D Taylor, Julia A Rissman, Emilie F Connelly, Jessica J eng AS4802/Autism Speaks/ F32 ES019404/ES/NIEHS NIH HHS/ R01 MH086711/MH/NIMH NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2012/06/19 Endocrinology. 2012 Aug; 153(8):3828-38. doi: 10.1210/en.2012-1195. Epub 2012 Jun 15" |