Abstract
Maternal exposure to environmental contaminants during pregnancy can profoundly influence the risk of developing cardiovascular disease in adult offspring. Our previous studies have demonstrated impaired cardiovascular health, microvascular reactivity, and cardiac function in fetal and young adult progeny after maternal inhalation of nano-sized titanium dioxide (nano-TiO2) aerosols during gestation. The present study was designed to evaluate the development of cardiovascular and metabolic diseases later in adulthood. Pregnant Sprague–Dawley rats were exposed to nano-TiO2 aerosols (~ 10 mg/m3, 134 nm median diameter) for 4 h per day, 5 days per week, beginning on gestational day (GD) 4 and ending on GD 19. Progeny were delivered in-house. Body weight was recorded weekly after birth. After 47 weeks, the body weight of exposed progeny was 9.4% greater compared with controls. Heart weight, mean arterial pressure, and plasma biomarkers of inflammation, dyslipidemia, and glycemic control were recorded at 3, 9 and 12 months of age, with no significant adaptations. While no clinical risk factors (i.e., hypertension, dyslipidemia, or systemic inflammation) emerged pertaining to the development of cardiovascular disease, we identified impaired endothelium-dependent and -independent arteriolar dysfunction and cardiac morphological alterations consistent with myocardial inflammation, degeneration, and necrosis in exposed progeny at 12 months. In conclusion, maternal inhalation of nano-TiO2 aerosols during gestation may promote the development of coronary disease in adult offspring.
Highlights
Maternal exposure to environmental contaminants during pregnancy can profoundly influence the risk of developing cardiovascular disease in adult offspring
The average body weight of nano-TiO2 exposed offspring was significantly higher compared with the average body weights of sham-control offspring in the 15-week moving average reported at week 47 (Fig. 1) (p < 0.01, two-way analysis of variance (ANOVA) followed by leastsignificant difference test (LSD) post hoc multiple comparison)
Average body weights of Engineered nanomaterials (ENM)-exposed offspring tended to be greater compared with average body weights of sham-controls during the maintenance phase of growth, these differences were not significant
Summary
Maternal exposure to environmental contaminants during pregnancy can profoundly influence the risk of developing cardiovascular disease in adult offspring. Our previous studies have demonstrated impaired cardiovascular health, microvascular reactivity, and cardiac function in fetal and young adult progeny after maternal inhalation of nano-sized titanium dioxide (nano-TiO2) aerosols during gestation. While no clinical risk factors (i.e., hypertension, dyslipidemia, or systemic inflammation) emerged pertaining to the development of cardiovascular disease, we identified impaired endothelium-dependent and -independent arteriolar dysfunction and cardiac morphological alterations consistent with myocardial inflammation, degeneration, and necrosis in exposed progeny at 12 months. Maternal inhalation of nano-TiO2 aerosols during gestation may promote the development of coronary disease in adult offspring. More recent studies demonstrate maternal exposure to environmental contaminants results in increased risk of adult disease in o ffspring[5]. Based on experimental evidence from inhalation studies, TiO2 has been classified by the International Agency for Research on Cancer (IARC) as possibly carcinogenic to h umans[18]
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