The Effect of FPR2 on the Regulation of Trophoblast Autophagy via the PI3K/AKT/mTOR Signaling Pathway in Preeclampsia

Preeclampsia (PE) is associated with significant maternal and fetal morbidity and mortality, with placental trophoblast dysfunction playing a central role in its pathogenesis. Autophagic imbalance impacts trophoblast function, and the regulatory role of formyl-peptide receptor 2 (FPR2) in trophoblast autophagy and placental function requires further investigation. We used the HTR8/SVneo cell line and Fpr2 knockout mice to explore the role of FPR2 in trophoblast function. The expression of FPR2 and autophagy levels were elevated in PE patients and models. FPR2 knockdown reversed the H₂O₂-induced inhibition of trophoblast function and downregulated autophagy-related proteins. H₂O₂ activated the PI3K/AKT/mTOR pathway, but this activation was reduced by FPR2 knockdown or 3-MA pretreatment. We demonstrate that FPR2 regulates trophoblast autophagy through the PI3K/AKT/mTOR signaling pathway, contributing to the development of PE. These findings may offer new insights into the prevention and treatment of PE.