Although nano-TiO2 has been extensively used in food industrial application, and in daily products for infants and children, its potential neurotoxicity presents a significant concern. As previous studies have demonstrated the neurological effects of nano-TiO2 in mice, the main objective of the current investigation was to establish the effects of prenatal exposure of nano-TiO2 on developing embryos and offspring. ICR female mice were orally administered (1, 2, and 3 mg/kg body weight) nano-TiO2 from prenatal day 2 to postnatal day 21. Morphological changes, learning and memory, and potential target molecules of neurodevelopmental toxicity in offspring mice of nano-TiO2-exposed mothers were examined. The results showed that nano-TiO2 could translocate from prenatally exposed maternal to offspring hippocampi, resulting in hippocampal damage including: a 29.07%-61.4% reduction in spatial recognition; a 22.55% -61.34% reduction in total dendritic length; a 53.57%-71.42% reduction in dendritic branch number; and a 27.72%-75.74% reduction in spine density in offspring CA1 pyramidal cells. Furthermore, expression of several proteins involved in dendritic development was decreased including: a 47.62%-73.81% in microtubule-associated proteins; a 14.58%-54.17% in mitotic kinesin-like protein 1; a 1.14%-31.82% in collapsin response mediator protein 3; a 65.17%-79.05% in neuregulin tyrosine kinase receptor 4; a 1.13%-76.92% in kinesin superfamily protein 17; and a 25.73%-61.4% in post synaptic density protein -95 in offspring hippocampi. Hippocampal neurons may present a major target of neurotoxicity in offspring following maternal exposure to nano-TiO2 during the prenatal period. Therefore, food application of nano-TiO2 should be performed with caution.
Fashui Hong, Yingjun Zhou, Jianhui Ji and Ling Wang