title: Maternal-engineered nanomaterial exposure disrupts progeny cardiac function and bioenergetics.
abstract: Nanomaterial production is expanding as new industrial and consumer applications are introduced. Nevertheless, the impacts of exposure to these compounds are not fully realized. The present study was designed to determine whether gestational nano-sized titanium dioxide exposure impacts cardiac and metabolic function of developing progeny. Pregnant Sprague-Dawley rats were exposed to nano-aerosols (~10 mg/m3, 130- to 150-nm count median aerodynamic diameter) for 7-8 nonconsecutive days, beginning at gestationalday 5-6Physiological and bioenergetic effects on heart function and cardiomyocytes across three time points, fetal (gestationalday 20), neonatal (4-10 days), and young adult (6-12 wk), were evaluated. Functional analysis utilizing echocardiography, speckle-tracking based strain, and cardiomyocyte contractility, coupled with mitochondrial energetics, revealed effects of nano-exposure. Maternal exposed progeny demonstrated a decrease in E- and A-wave velocities, with a 15% higher E-to-A ratio than controls. Myocytes isolated from exposed animals exhibited ~30% decrease in total contractility, departure velocity, and area of contraction. Bioenergetic analysis revealed a significant increase in proton leak across all ages, accompanied by decreases in metabolic function, including basal respiration, maximal respiration, and spare capacity. Finally, electron transport chain complex I and IV activities were negatively impacted in the exposed group, which may be linked to a metabolic shift. Molecular data suggest that an increase in fatty acid metabolism, uncoupling, and cellular stress proteins may be associated with functional deficits of the heart. In conclusion, gestational nano-exposure significantly impairs the functional capabilities of the heart through cardiomyocyte impairment, which is associated with mitochondrial dysfunction.NEW & NOTEWORTHYCardiac function is evaluated, for the first time, in progeny following maternal nanomaterial inhalation. The findings indicate that exposure to nano-sized titanium dioxide (nano-TiO2) during gestation negatively impacts cardiac function and mitochondrial respiration and bioenergetics. We conclude that maternal nano-TiO2inhalation contributes to adverse cardiovascular health effects, lasting into adulthood.
authors.affiliation: Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia.|Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, West Virginia.
authors.forename: Quincy A
authors.initials: QA
authors.lastname: Hathaway
authors.affiliation: Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia.
authors.forename: Cody E
authors.initials: CE
authors.lastname: Nichols
authors.affiliation: Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia.|Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, West Virginia.
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Shepherd
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, West Virginia.
authors.forename: Phoebe A
authors.initials: PA
authors.lastname: Stapleton
authors.affiliation: Department of Cancer Cell Biology, West Virginia University School of Medicine; Morgantown, West Virginia; and.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: McLaughlin
authors.affiliation: Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia.
authors.forename: Janelle C
authors.initials: JC
authors.lastname: Stricker
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, West Virginia.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Rellick
authors.affiliation: Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia.
authors.forename: Mark V
authors.initials: MV
authors.lastname: Pinti
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, West Virginia.
authors.forename: Alaeddin B
authors.initials: AB
authors.lastname: Abukabda
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, West Virginia.
authors.forename: Carroll R
authors.initials: CR
authors.lastname: McBride
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, West Virginia.
authors.forename: Jinghai
authors.initials: J
authors.lastname: Yi
authors.affiliation: Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia.|Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, West Virginia.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Stine
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, West Virginia.|Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, West Virginia.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Nurkiewicz
authors.affiliation: Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia; jhollander@hsc.wvu.edu.|Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, West Virginia.
authors.forename: John M
authors.initials: JM
authors.lastname: Hollander
mesh_terms: D000375:Aging; D000818:Animals; D004452:Echocardiography; D042967:Electron Transport Complex I / Q000187:drug effects / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000187:drug effects / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging*; D006331:Heart Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000473:pathology; D006334:Heart Function Tests; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects; D049329:Nanostructures / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014025:Titanium / Q000633:toxicity
chemical_list: C009495:titanium dioxide; D014025:Titanium; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I
keywords: cardiac dysfunction; mitochondria; nanomaterials; pregnancy