In Utero Nano-Titanium Dioxide Exposure Results in Sexually Dimorphic Weight Gain and Cardiovascular Function in Offspring

Engineered nanomaterials (ENM) are capable of crossing the placental barrier and accumulating in fetal tissue. Specifically, the ENM nano-titanium dioxide (nano-TiO₂), has been shown to accumulate in placental and fetal tissue, resulting in decreased birthweight in pups. Additionally, nano-TiO₂ is an established cardiac toxicant and regulator of glucose homeostasis, and exposure in utero may lead to serious maladaptive responses in cardiac development and overall metabolism. The current study examines weight gain and cardiac function in male and female Sprague-Dawley rats exposed to 12 mg/m³ nano-TiO₂ or filtered air for 6 non-consecutive days in utero between gestational days 12-19. These animals were randomly assigned to receive a grain-based or high-fat diet (60%) between postnatal weeks 12-24 to examine the propensity for weight gain and cardiac response as adults. Our results show a sexually dimorphic response to weight gain with male rats gaining more weight after high-fat diet following in utero nano-TiO₂ exposure, and female rats gaining less weight on the high-fat diet respective of exposure. Male rats exposed to nano-TiO₂ in utero had reduced ejection fraction prior to diet when compared to air controls. Female rats subjected to in utero nano-TiO₂ exposure showed a significant decrease in cardiac output following 12 weeks of high-fat diet. Development of cardiovascular impairments and ultimately cardiac dysfunction and disease following in utero exposures highlights the need for occupational and environmental monitoring of nanoparticulate exposure.