title: Developmental programming: Interaction between prenatal BPA and postnatal overfeeding on cardiac tissue gene expression in female sheep.
abstract: Epidemiologic studies and studies in rodents point to potential risks from developmental exposure to BPA on cardiometabolic diseases. Furthermore, it is becoming increasingly evident that the manifestation and severity of adverse outcomes is the result of interaction between developmental insults and the prevailing environment. Consistent with this premise, recent studies in sheep found prenatal BPA treatment prevented the adverse effects of postnatal obesity in inducing hypertension. The gene networks underlying these complex interactions are not known. mRNA-seq of myocardium was performed on four groups of four female sheep to assess the effects of prenatal BPA exposure, postnatal overfeeding and their interaction on gene transcription, pathway perturbations and functional effects. The effects of prenatal exposure to BPA, postnatal overfeeding, and prenatal BPA with postnatal overfeeding all resulted in transcriptional changes (85-141 significant differentially expressed genes). Although the effects of prenatal BPA and postnatal overfeeding did not involve dysregulation of many of the same genes, they affected a remarkably similar set of biological pathways. Furthermore, an additive or synergistic effect was not found in the combined treatment group, but rather prenatal BPA treatment led to a partial reversal of the effects of overfeeding alone. Many genes previously known to be affected by BPA and involved in obesity, hypertension, or heart disease were altered following these treatments, and AP-1, EGR1, and EGFR were key hubs affected by BPA and/or overfeeding. Environ. Mol. Mutagen. 58:4-18, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Departments of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan.
authors.forename: L A
authors.initials: LA
authors.lastname: Koneva
authors.affiliation: Department of Pediatrics, Texas Tech Health Sciences Permian Basin, Odessa, Texas.
authors.forename: A K
authors.initials: AK
authors.lastname: Vyas
authors.affiliation: Departments of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan.
authors.forename: R C
authors.initials: RC
authors.lastname: McEachin
authors.affiliation: Departments of Pediatrics, University of Michigan, Ann Arbor, Michigan.
authors.forename: M
authors.initials: M
authors.lastname: Puttabyatappa
authors.affiliation: Departments of Environmental Health, University of Cincinnati, Cincinnati, Ohio.|Departments of Pharmacology and Cell Biophysics, University of Cincinnati, Cincinnati, Ohio.
authors.forename: H-S
authors.initials: HS
authors.lastname: Wang
authors.affiliation: Departments of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan.
authors.forename: M A
authors.initials: MA
authors.lastname: Sartor
authors.affiliation: Departments of Pediatrics, University of Michigan, Ann Arbor, Michigan.
authors.forename: V
authors.initials: V
authors.lastname: Padmanabhan
mesh_terms: D000821:Animal Feed; D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D001724:Birth Weight / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D047109:Fetal Development / Q000187:drug effects* / Q000235:genetics; D020869:Gene Expression Profiling; D059647:Gene-Environment Interaction; D005865:Gestational Age; D009206:Myocardium / Q000378:metabolism*; D009765:Obesity / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D012756:Sheep; D059467:Transcriptome / Q000187:drug effects*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: DOHAD; cardiometabolic diseases; endocrine disruptors; myocardium; obesity