Prenatal exposure to TiO 2 nanoparticles in mice causes behavioral deficits with relevance to autism spectrum disorder and beyond

摘要

Environmental factors are involved in the etiology of autism spectrum disorder (ASD) and may contribute to the raise in its incidence rate. It is currently unknown whether the increasing use of nanoparticles such as titanium dioxide (TiO₂ NPs) in consumer products and biomedical applications may play a role in these associations. While nano-sized TiO₂ is generally regarded as safe and non-toxic, excessive exposure to TiO₂ NPs may be associated with negative health consequences especially when occurring during sensitive developmental periods. To test if prenatal exposure to TiO₂ NPs alters fetal development and behavioral functions relevant to ASD, C57Bl6/N dams were subjected to a single intravenous injection of a low (100?μg) or high (1000?μg) dose of TiO₂ NPs or vehicle solution on gestation day 9. ASD-related behavioral functions were assessed in the offspring using paradigms that index murine versions of ASD symptoms. Maternal exposure to TiO₂ NPs led to subtle and dose-dependent impairments in neonatal vocal communication and juvenile sociability, as well as a dose-dependent increase in prepulse inhibition of the acoustic startle reflex of both sexes. These behavioral alterations emerged in the absence of pregnancy complications. Prenatal exposure to TiO₂ NPs did not cause overt fetal malformations or changes in pregnancy outcomes, nor did it affect postnatal growth of the offspring. Taken together, our study provides a first set of preliminary data suggesting that prenatal exposure to nano-sized TiO₂ can induce behavioral deficits relevant to ASD and related neurodevelopmental disorders without inducing major changes in physiological development. If extended further, our preclinical findings may provide an incentive for epidemiological studies examining the role of prenatal TiO₂ NPs exposure in the etiology of ASD and other neurodevelopmental disorders.