title: Lifelong exposure to bisphenol a alters cardiac structure/function, protein expression, and DNA methylation in adult mice.
abstract: Bisphenol A (BPA) is an estrogenizing endocrine disruptor compound of concern. Our objective was to test whether lifelong BPA would impact cardiac structure/function, calcium homeostasis protein expression, and the DNA methylation of cardiac genes. We delivered 0.5 and 5.0 µg/kg/day BPA lifelong from gestation day 11 or 200 µg/kg/day from gestation day 11 to postnatal day 21 via the drinking water to C57bl/6n mice. BPA 5.0 males and females had increased body weight, body mass index, body surface area, and adiposity. Echocardiography identified concentric remodeling in all BPA-treated males. Systolic and diastolic cardiac functions were essentially similar, but lifelong BPA enhanced male and reduced female sex-specific differences in velocity of circumferential shortening and ascending aorta velocity time integral. Diastolic blood pressure was increased in all BPA females. The calcium homeostasis proteins sarcoendoplasmic reticulum ATPase 2a (SERCA2a), sodium calcium exchanger-1, phospholamban (PLB), phospho-PLB, and calsequestrin 2 are important for contraction and relaxation. Changes in their expression suggest increased calcium mobility in males and reduced calcium mobility in females supporting the cardiac function changes. DNA methyltransferase 3a expression was increased in all BPA males and BPA 0.5 females and reduced in BPA 200 females. Global DNA methylation was increased in BPA 0.5 males and reduced in BPA 0.5 females. BPA induced sex-specific altered DNA methylation in specific CpG pairs in the calsequestrin 2 CpG island. These results suggest that continual exposure to BPA impacts cardiac structure/function, protein expression, and epigenetic DNA methylation marks in males and females.
authors: Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, Québec H3T 1E2, Canada.
authors: Bhavini B
authors: BB
authors: Patel
authors: Mohamad
authors: M
authors: Raad
authors: Igal A
authors: IA
authors: Sebag
authors: Lorraine E
authors: LE
authors: Chalifour
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects*; D000090205:DNA Methyltransferase 3A; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D005865:Gestational Age; D006321:Heart / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D006334:Heart Function Tests; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics; D012737:Sex Factors; D019831:Sodium-Calcium Exchanger / Q000235:genetics; D013997:Time Factors; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D000090205:DNA Methyltransferase 3A; D052244:Endocrine Disruptors; D010636:Phenols; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019831:Sodium-Calcium Exchanger; C506948:Atp2a2 protein, rat; C000715535:Dnmt3a protein, mouse; C503872:caisequestrin 2, rat; C110374:sodium-calcium exchanger 1; C006780:bisphenol A; D000098826:Bisphenol A Compounds