Effects of prenatal bisphenol-A exposure and postnatal overfeeding on cardiovascular function in female sheep.
Bisphenol-A (BPA) is a widely used endocrine-disrupting chemical. Prenatal exposure to BPA is known to affect birth weight, but its impact on the cardiovascular system has not been studied in detail. In this study, we investigated the effects of prenatal BPA treatment and its interaction with postnatal overfeeding on the cardiovascular system. Pregnant sheep were given daily subcutaneous injections of corn oil (control) or BPA (0.5 mg/kg/day in corn oil) from day 30 to day 90 of gestation. A subset of female offspring of these dams were overfed to increase body weight to ~30% over that of normal fed controls. Cardiovascular function was assessed using non-invasive echocardiography and cuff blood pressure (BP) monitoring at 21 months of age. Ventricular tissue was analyzed for gene expression of cardiac markers of hypertrophy and collagen at the end of the observation period. Prenatal BPA exposure had no significant effect on BP or morphometric measures. However, it increased atrial natriuretic peptide gene expression in the ventricles and reduced collagen expression in the right ventricle. Overfeeding produced a marked increase in body weight and BP. There were compensatory increases in left ventricular area and internal diameter. Prenatal BPA treatment produced a significant increase in interventricular septal thickness when animals were overfed. However, it appeared to block the increase in BP and left ventricular area caused by overfeeding. Taken together, these results suggest that prenatal BPA produces intrinsic changes in the heart that are capable of modulating morphological and functional parameters when animals become obese in later life.
1Department of Veterinary Biosciences and Diagnostic Imaging,College of Veterinary Medicine,University of Georgia,Athens,GA,USA.
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MohanKumar
2Department of Small Animal Clinical Sciences,Michigan State University,East Lansing, MI,USA.
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Rajendran
3Pediatrics and Human Development,Michigan State University,East Lansing, MI,USA.
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Vyas
3Pediatrics and Human Development,Michigan State University,East Lansing, MI,USA.
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Hoang
4Pharmacology & Toxicology,Michigan State University,East Lansing, MI,USA.
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Asirvatham-Jeyaraj
5Department of Animal Sciences,Michigan State University,East Lansing, MI,USA.
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Veiga-Lopez
2Department of Small Animal Clinical Sciences,Michigan State University,East Lansing, MI,USA.
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Olivier
6Department of Pediatrics,University of Michigan,Ann Arbor, MI,USA.
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Padmanabhan
1Department of Veterinary Biosciences and Diagnostic Imaging,College of Veterinary Medicine,University of Georgia,Athens,GA,USA.
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MohanKumar
D000395:Air Pollutants, Occupational / Q000009:adverse effects*; D000818:Animals; D001559:Benzhydryl Compounds / Q000009:adverse effects*; D001724:Birth Weight; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D005260:Female; D044343:Overnutrition / Q000503:physiopathology*; D010636:Phenols / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D012756:Sheep; D000098826:Bisphenol A Compounds
D000395:Air Pollutants, Occupational; D001559:Benzhydryl Compounds; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
blood pressure; cardiac gene expression; cardio-metabolic programming; echocardiography; endocrine disruptors