The Receptor Activator of Nuclear Factor κB Ligand (RANKL) Influences the Biological Behavior of Trophoblasts through the PI3K/Akt Signaling Pathway

Introduction: Abnormal function of trophoblasts is a primary cause of recurrent spontaneous abortion (RSA). However, the underlying molecular mechanisms remains unclear, and further explanation is urgently needed. This study aims to explore the effect and potential regulatory mechanisms of RANKL in the biological function of trophoblasts. Methods: Immunohistochemical was conducted on villous tissues frome RSA patients and people who underwent artificial abortion. Cell proliferation, migration, and invasion were assessed in HTR-8/SVneo and JEG-3 cells using CCK-8, scratch wound healing, and transwell assays. Protein expression was analyzed by Western blotting. Results: The expression of RANKL was significantly lower in villus of RSA patients compared to healthy controls. Recombinant human RANKL (rhRANKL) promoted the proliferation, migration and invasion of trophoblasts, while rhOPG, α-RANKL and MK-2206 (Akt ihibitor) alleviated the effect of rhRANK. Moreover, it may exert the effect through the PI3K/Akt signaling pathway. Conclusions: Our results demonstrated that RANKL promoted trophoblast proliferation, invasion, and migration via the PI3K/Akt pathway, highlighting a potential novel target for the physiological mechanisms of RSA.