Maternal-engineered nanomaterial exposure disrupts progeny cardiac function and bioenergetics

Author:

Hathaway Quincy A.12,Nichols Cody E.1,Shepherd Danielle L.12,Stapleton Phoebe A.3,McLaughlin Sarah L.4,Stricker Janelle C.1,Rellick Stephanie L.3,Pinti Mark V.1,Abukabda Alaeddin B.3,McBride Carroll R.3,Yi Jinghai3,Stine Seth M.12,Nurkiewicz Timothy R.32,Hollander John M.12

Affiliation:

1. Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia;

2. Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, West Virginia

3. Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, West Virginia;

4. Department of Cancer Cell Biology, West Virginia University School of Medicine; Morgantown, West Virginia; and

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 gestational day 5–6. Physiological and bioenergetic effects on heart function and cardiomyocytes across three time points, fetal (gestational day 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 & NOTEWORTHY Cardiac 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-TiO2 inhalation contributes to adverse cardiovascular health effects, lasting into adulthood. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/gestational-nanomaterial-exposure-and-cardiac-dysfunction/ .

Funder

National Science Foundation (NSF)

HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)

HHS | NIH | National Institute of Environmental Health Sciences (NIEHS)

American Heart Association (AHA)

HHS | NIH | National Center for Research Resources (NCRR)

HHS | NIH | National Institute of General Medical Sciences (NIGMS)

Publisher

American Physiological Society

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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