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Abstract Title:

Transgenerational effects of Bisphenol A on gene expression and DNA methylation of imprinted genes in brain.

Abstract Source:

Endocrinology. 2017 Nov 17. Epub 2017 Nov 17. PMID: 29165653

Abstract Author(s):

Zuzana Drobná, Anne D Henriksen, Jennifer T Wolstenholme, Catalina Montiel, Philip S Lambeth, Stephen Shang, Erin P Harris, Changqing Zhou, Jodi A Flaws, Mazhar Adli, Emilie F Rissman

Article Affiliation:

Zuzana Drobná

Abstract:

Bisphenol A (BPA) is a ubiquitous man-made endocrine disrupting compound (EDC). Developmental exposure to BPA changes behavioral and reproductive phenotypes and these effects can last for generations. We exposed embryos to BPA producing two lineages: controls and BPA-exposed. In the third generation (F3), brain tissues containing the preoptic area, the bed nucleus of the stria terminalis, and the anterior hypothalamus were collected. RNA sequencing (RNA-Seq) and subsequent data analyses revealed 50 differentially regulated genes in the brains of F3 juveniles from BPA- versus control-lineages. BPA exposure can lead to loss of imprinting, and one of the two imprinted genes in our data set, maternally expressed 3 (Meg3) has been associated with EDCs and neurobehavioral phenotypes. We used quantitative PCR to examine the two imprinted genes in our data set, Meg3, and microRNA-containing gene, Mirg (residing in the same loci). Confirming the RNA-Seq, Meg3 mRNA was higher in F3 brains from the BPA-lineage as compared with control brains. This was true in brains from mice produced using two different BPA paradigms. Next, we used pyrosequencing to probe differentially methylated regions of Meg3. This is the first report of transgenerational effects of BPA on imprinted genes in brain. Given these results, and data on Meg3 methylation in humans, we suggest this gene may be a biomarker indicative of early life environmental perturbation.

Study Type : Animal Study

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