Cardiovascular Susceptibility in Offspring After Maternal Engineered Nanomaterial Exposure

Abstract

Cardiovascular disease (CVD) is the leading cause of death worldwide and associated with many genetic and lifestyle risk factors. The maternal health and fetal milieu during gestation has been explored as a contributing factor to progeny health. Engineered nanomaterials (ENM) are manufactured within the nanoscale (<100 nm in one dimension) to take advantage of specific physiochemical properties. Exposure to these materials has become more prolific given their pervasiveness in domestic applications, yet the outcomes during pregnancy and for developing young are currently unknown. Gestational ENM exposure led to impairments in uterine microvascular reactivity in early studies, indicative of the development of a hostile gestational environment. The Barker Hypothesis theorizes that development is such an environment will influence cardiovascular health later in life.Studies were initiated to assess the cardiovascular health during growth from a late‐stage fetus to young adult after maternal ENM inhalation. Pregnant, healthy Sprague‐Dawley rats were exposed to nano‐sized titanium dioxide aerosols (10.4±0.1 mg/m3 for 4h, aerodynamic diameter of 136.5±1.4 nm, calculated daily pulmonary deposition of 39.7±1 μg, initiated on gestational day [GD] 5.78±0.13 for 7.78±0.26 days of the remaining pregnancy). As indices of litter health, the number of fetal pups on GD 20 did not differ between control and exposed (12.2±0.9 vs. 10.8±1.5); however, the size of the placenta (0.76g±0.02 vs. 0.68±0.02) and number of surviving pups (11±0.7 vs. 6±1) were significantly different. As microvascular health can characterize early cardiovascular health, reactivity was assessed via a pressurized isolated microvessel preparation where the arterioles of the tail (fetal [GD 20], neonate [6±0.48d] or heart (weanling [25.7±0.9d], juvenile [7.64±0.4w], adult [10.36±0.34w]) progeny were dissected, excised, and evaluated in response to chemical stimuli to calculate endothelium‐dependent (acetylcholine [10−9–10−4 M]), ‐independent (spermine‐NONOate [10−9–10−4 M]), and vascular smooth muscle (phenylephrine [10−9–10−4 M]) function. Significant temporal impairments in endothelium‐dependent reactivity were identified in exposed fetal (−37.2%±7.3), juvenile (−29.1%±11.3), and adult (−59.3%±17.1 vs. control, respectively) progeny. Further, studies of mitochondrial stress reveal significant reductions in calculated ATP production of isolated cardiomyocytes during development where fetal (23%±3), neonate (83%±3), weanling and juvenile (63%±9), and young adult (75%±2) measurements are below control. Overall, exposure to ENM during gestation may increase CVD susceptibility, thereby compromising health of future generations.Support or Funding InformationNIH‐R00‐ES024783 (PAS); P30‐ES005022This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.