F-53B-induced placental vascular endothelial dysfunction leads to intrauterine growth retardation of fetal mice
- Ecotoxicol Environ Saf. 2025 Dec:308:119467. doi: 10.1016/j.ecoenv.2025.119467.
- 1. Institute for Chemical Carcinogenesis, School of Public Health, Guangzhou Medical University, Guangzhou 511436, China.
- 2. National Engineering Research Center for Healthcare Devices, Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou 510316, China.
- 3. Laboratory of Epigenetics and Metabolism, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan.
- 4. Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
- 5. Third Clinical School, Guangzhou Medical University, Guangzhou 511436, China.
- 6. Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou 510632, China. Electronic address: [email protected].
- 7. National Engineering Research Center for Healthcare Devices, Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou 510316, China. Electronic address: [email protected].
Chlorinated polyfluoroalkyl ether sulfonic acid (Cl-PFESAs, trade name F-53B) is a perfluorinated compound substitute whose concentration in the placenta is negatively correlated with neonatal weight, yet its toxic mechanism remains unclear. In this study, pregnant C57BL/6 mice were orally administered with 5, 50, and 500 μg/kg of F-53B from gestational days 0.5 to 17.5. By integrating in vivo imaging and laser scattering imaging, we found that F-53B exposure resulted in increased placental barrier permeability and reduced maternal-fetal blood perfusion, which may underline the observed fetal growth retardation. Pathological and immunofluorescence examination revealed that F-53B may trigger the endothelial-to-mesenchymal transition (EndMT) in the placental labyrinth vasculature. Combining RNA Sequencing and trophoblast-endothelial cell co-culture experiments, we identified EndMT induced placental vascular injury as a key mechanism in F-53B induced fetal growth retardation, potentially initiated by interfered pro-angiogenic function of trophoblasts. Our results indicate that EndMT driven placental vascular injury is a key event in F-53B-induced fetal growth restriction, providing a new perspective on the developmental toxicity mechanism of F-53B.