Melatonin affects trophoblast epithelial-to-mesenchymal transition and oxidative damage resistance by modulating GDF15 expression to promote embryo implantation

• DOI: 10.1038/s42003-025-07834-1
• Publication Date: 2025-03-08T13:15:22Z
• Authors: Guang Yang; Guidong Yao; Huihui Wang; Ran Jiang; Junnan Fang; Jingyi Hu; Yue Kong; Haixia Jin; Wenyan Song; Zhaoting Wu; Xianju Huang; Yingpu Sun
• Keywords: Trophoblast

Melatonin is widely observed in the female reproductive system and regulates trophoblast cell functions, but its effects on embryo implantation underlying mechanisms are not well understood. By constructing an vitro culture model, we found that melatonin enhances migration human mouse cells. It also significantly promoted HTR-8/SVneo proliferation, inhibited apoptosis, enhanced migration, mitigated oxidative damage. Further investigation revealed increased rate of spheroids by promotes epithelial-mesenchymal transition (EMT) via growth differentiation factor 15 (GDF15)–mothers against decapentaplegic homolog 2/3 (SMAD2/3) pathway. Additionally, levels glutathione peroxidase 4 (GPX4) (GSH) cells upregulating expression GDF15, inhibiting reactive oxygen species (ROS) accumulation, increasing mitochondrial membrane potential, thus suppressing apoptosis during stress. In conclusion, EMT GDF15-SMAD2/3 pathway partially induces GPX4 through GDF15 to enhance damage resistance These findings highlight melatonin's regulatory role suggest new avenues for exploring biological reproduction clinical applications. GDF15-mediated activation SMAD2/3