Maternal exposure to nano-titanium dioxide impedes fetal development via endothelial-to-mesenchymal transition in the placental labyrinth in mice

作者：Xianjie Li, Yinger Luo, Di Ji, Zhuyi Zhang, Shili Luo, Ya Ma, Wulan Cao, Chunwei Cao, Phei Er Saw, Hui Chen, Yanhong Wei · 发表于：Particle and Fibre Toxicology · 年份：2023 · DOI：10.1186/s12989-023-00549-3 · 被引用次数：19 · 研究领域：Pregnancy and preeclampsia studies、Anesthesia and Neurotoxicity Research、Renal and Vascular Pathologies

Abstract Background Extensive production and usage of commercially available products containing TiO 2 NPs have led to accumulation in the human body. The deposition of TiO 2 NPs has even been detected in the human placenta, which raises concerns regarding fetal health. Previous studies regarding developmental toxicity have frequently focused on TiO 2 NPs < 50 nm, whereas the potential adverse effects of large-sized TiO 2 NPs received less attention. Placental vasculature is essential for maternal–fetal circulatory exchange and ensuring fetal growth. This study explores the impacts of TiO 2 NPs (100 nm in size) on the placenta and fetal development and elucidates the underlying mechanism from the perspective of placental vasculature. Pregnant C57BL/6 mice were exposed to TiO 2 NPs by gavage at daily dosages of 10, 50, and 250 mg/kg from gestational day 0.5–16.5. Results TiO 2 NPs penetrated the placenta and accumulated in the fetal mice. The fetuses in the TiO 2 NP-exposed groups exhibited a dose-dependent decrease in body weight and length, as well as in placental weight and diameter. In vivo imaging showed an impaired placental barrier, and pathological examinations revealed a disrupted vascular network of the labyrinth upon TiO 2 NP exposure. We also found an increase in gene expression related to the transforming growth factor-β (TGF-β) -SNAIL pathway and the upregulation of mesenchymal markers, accompanied by a reduction in endothelial markers. In addition, TiO 2 NPs ...