title: Impact of gestational bisphenol A on oxidative stress and free fatty acids: Human association and interspecies animal testing studies.
abstract: Bisphenol A (BPA) is a high production volume chemical and an endocrine disruptor. Developmental exposures to BPA have been linked to adult metabolic pathologies, but the pathways through which these disruptions occur remain unknown. This is a comprehensive interspecies association vs causal study to evaluate risks posed by prenatal BPA exposure and to facilitate discovery of biomarkers of relevance to BPA toxicity. Samples from human pregnancies during the first trimester and at term, as well as fetal and/or adult samples from prenatally BPA-treated sheep, rats, and mice, were collected to assess the impact of BPA on free fatty acid and oxidative stress dynamics. Mothers exposed to higher BPA during early to midpregnancy and their matching term cord samples displayed increased 3-nitrotyrosine (NY), a marker of nitrosative stress. Maternal samples had increased palmitic acid, which was positively correlated with NY. Sheep fetuses and adult sheep and rats prenatally exposed to a human-relevant exposure dose of BPA showed increased systemic nitrosative stress. The strongest effect of BPA on circulating free fatty acids was observed in adult mice in the absence of increased oxidative stress. This is the first multispecies study that combines human association and animal causal studies assessing the risk posed by prenatal BPA exposure to metabolic health. This study provides evidence of the induction of nitrosative stress by prenatal BPA in both the mother and fetus at time of birth and is thus supportive of the use of maternal NY as a biomarker for offspring health.
authors.affiliation: Department of Pediatrics (A.V.-L., V.P.), University of Michigan, Ann Arbor, Michigan 48109; Department of Internal Medicine (S.P., L.Z.), University of Michigan, Ann Arbor, Michigan 48109; Wadsworth Center (K.K.), New York State Department of Health, Albany, New York 12201; Department of Biological Sciences (H.B.P.), North Carolina State University, Raleigh, North Carolina 27695; and Department of Environmental Health Sciences (D.C.D.), University of Michigan, Ann Arbor, Michigan 48109.
authors.forename: Almudena
authors.initials: A
authors.lastname: Veiga-Lopez
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Pennathur
authors.forename: Kurunthachalam
authors.initials: K
authors.lastname: Kannan
authors.forename: Heather B
authors.initials: HB
authors.lastname: Patisaul
authors.forename: Dana C
authors.initials: DC
authors.lastname: Dolinoy
authors.forename: Lixia
authors.initials: L
authors.lastname: Zeng
authors.forename: Vasantha
authors.initials: V
authors.lastname: Padmanabhan
mesh_terms: D000328:Adult; D000818:Animals; D001559:Benzhydryl Compounds / Q000097:blood / Q000633:toxicity*; D015415:Biomarkers; D004785:Environmental Pollutants; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005333:Fetus / Q000187:drug effects; D006801:Humans; D007018:Hypopituitarism; D018811:Maternal Exposure; D051379:Mice; D018384:Oxidative Stress; D010636:Phenols / Q000097:blood / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D013045:Species Specificity; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D015415:Biomarkers; D004785:Environmental Pollutants; D005230:Fatty Acids, Nonesterified; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds