Insight into perfluorooctanoic acid-induced impairment of mouse embryo implantation via single-cell RNA-seq

Perfluorooctanoic acid (PFOA) is an environmentally persistent chemical that poses significant risks to human health. Studies have shown that PFOA affects female reproduction, but the specific impact on endometrial receptivity and the underlying mechanisms remain poorly understood. In this study, we investigated the effects of low-dose PFOA exposure through drinking water on endometrial receptivity in a murine model. Our results demonstrate that PFOA exposure significantly impaired endometrial receptivity, which led to a marked decrease in embryo implantation rates. Utilizing single-cell RNA sequencing technology, we conducted a comprehensive analysis that revealed specific mechanisms by which PFOA disrupts the function and development of endometrial epithelial cells. Notably, we identified dysregulation of the ANGPTL (angiopoietin-like) signaling pathway, which is critical for communication between endometrial stromal and epithelial cells, ultimately contributing to embryo implantation failure. These findings provide novel insights into the reproductive toxicity of PFOA and highlight potential targets for therapeutic interventions aimed at addressing infertility associated with environmental contaminants.