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 current study was designed to determine whether gestational nano-TiO2 exposure impacts cardiac and metabolic function of developing progeny. Pregnant Sprague Dawley rats were exposed to nano-TiO2 aerosols (~10 mg/m3, 130 - 150 nm count median aerodynamic diameter) for 7-8 non-consecutive 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 weeks) were evaluated. Functional analysis utilizing echocardiography, speckle-tracking based strain, and cardiomyocyte contractility coupled with mitochondrial energetics revealed effects of nano-TiO2 exposure. Maternal exposed progeny demonstrated a decrease in E and A wave velocities with a 15% higher E/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 suggests 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-TiO2 exposure significantly impairs the functional capabilities of the heart through cardiomyocyte impairment, which is associated with mitochondrial dysfunction.
- cardiac dysfunction
- Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology