Stromal cell decidualization and embryo implantation: a vulnerable step leading to successful pregnancy

Endometrial stromal cell decidualization is a crucial step in endometrial remodeling during pregnancy. Decidualization is controlled by orchestrated ovarian hormones, followed by the activation of various downstream signaling pathways. Accumulating evidence has shown multiple functions of decidualized endometrial stromal cells during embryo implantation, including tissue remodeling, antioxidative stress, angiogenesis, and immune tolerance. The distinct secretomes of decidualized stromal cells also reveal their intensive interactions with epithelial, endothelial, and immune cells. However, aberrant decidualization leads to pregnancy failures, such as recurrent pregnancy loss and repeated implantation failure. This review aimed to provide an overview of the molecular mechanisms underlying the divergent functions of decidualized endometrial stromal cells and their potential clinical applications. Moreover, the use of single-cell RNA sequencing data further enhances our understanding of these biological processes. This review discusses decidualization-related signaling pathways that serve as potential therapeutic targets for treating implantation failure in in vitro fertilization and provides novel approaches to investigate the underlying causes of female infertility.