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

Authors :
Li, Xianjie
Luo, Yinger
Ji, Di
Zhang, Zhuyi
Luo, Shili
Ma, Ya
Cao, Wulan
Cao, Chunwei
Saw, Phei Er
Chen, Hui
Wei, Yanhong
Source :
Particle & Fibre Toxicology; 12/11/2023, Vol. 20 Issue 1, p1-15, 15p
Publication Year :
2023

Abstract

Background: Extensive production and usage of commercially available products containing TiO<subscript>2</subscript> NPs have led to accumulation in the human body. The deposition of TiO<subscript>2</subscript> 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<subscript>2</subscript> NPs < 50 nm, whereas the potential adverse effects of large-sized TiO<subscript>2</subscript> NPs received less attention. Placental vasculature is essential for maternal–fetal circulatory exchange and ensuring fetal growth. This study explores the impacts of TiO<subscript>2</subscript> 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<subscript>2</subscript> NPs by gavage at daily dosages of 10, 50, and 250 mg/kg from gestational day 0.5–16.5. Results: TiO<subscript>2</subscript> NPs penetrated the placenta and accumulated in the fetal mice. The fetuses in the TiO<subscript>2</subscript> 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<subscript>2</subscript> 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<subscript>2</subscript> NPs enhanced the gene expression responsible for the endothelial-to-mesenchymal transition (EndMT) in cultured human umbilical vein endothelial cells, whereas SNAIL knockdown attenuated the induction of EndMT phenotypes. Conclusion: Our study revealed that maternal exposure to 100 nm TiO<subscript>2</subscript> NPs disrupts placental vascular development and fetal mice growth through aberrant activation of EndMT in the placental labyrinth. These data provide novel insight into the mechanisms of developmental toxicity posed by NPs. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
17438977
Volume :
20
Issue :
1
Database :
Complementary Index
Journal :
Particle & Fibre Toxicology
Publication Type :
Academic Journal
Accession number :
174095894
Full Text :
https://doi.org/10.1186/s12989-023-00549-3