Nano-TiO₂ retarded fetal development by inhibiting transplacental transfer of thyroid hormones in rats

The potential toxicity of nano-TiO₂ (nTiO₂) in the next generation of organisms is important for the environmental toxicological profile of nTiO₂. nTiO₂ has been shown to disrupt maternal thyroid hormone metabolism, whereas the effects of prenatal exposure to nTiO₂ on the transplacental transfer of thyroid hormones (THs) to the fetus have not been clarified. In this study, pregnant SD rats at gestation days (GDs) 0-17 were daily orally administered with 6.17, 12.34, 61.70, and 308.50 mg kg⁻¹ of nTiO₂ (29.6 ± 8.1 nm). Results showed that nTiO₂ exposure could inhibit the development of rat placenta and fetus at GD 18. Notably, THs (T₃ and T₄) were highly accumulated (increased by 19-90%) in the placenta. The retention of placental THs may be related to the down-regulation of TH transporters. nTiO₂ could induce oxidative stress on the maternal liver where TH transporters are produced. Genes encoding for TH transporters were mostly down-regulated by 29-65% and a decreased abundance of these transporters in the placenta was observed. An increased concentration of titanium can be observed in the placenta and fetus and subsequently the vascularization of labyrinth tissue was impaired. These findings imply that prenatal exposure to nTiO₂ in rats at levels converted from the human daily dietary level might restrict the transplacental transfer of THs and compromise placental function, thus inhibiting fetal growth and development, which could have implications for human health and safety.