Transcriptional regulation in decidualized endometrial stromal cells

Abstract

Endometrial decidualization is essential for embryo implantation and maintenance of pregnancy. A defect in decidualization leads to infertility, miscarriage, and perinatal diseases such as hypertensive disorders of pregnancy. Progesterone (P), secreted from the corpus luteum after ovulation, causes morphological and functional differentiation of endometrial stromal cells (ESCs). The Heart and neural crest derivatives-expressed transcript 2 (HAND2) in ESCs is one of transcriptional regulators that are directly regulated by the P receptor. The increase in HAND2 activity regulates the production and secretion of angiogenic factors and cytokines in ESCs. Through these factors, ESCs interact with vascular endothelial cells and immune cells, contributing to the establishment of vasculature and immune tolerance. We have reported that HAND2 in ESCs may contribute to vasculature in the secretory endometrium by suppressing fibroblast growth factor (FGF9)-FGF receptor signaling, thereby reducing angiopoietin 2 (ANGPT2) production. Furthermore, we found that HAND2 also plays an important role in the establishment of immune tolerance by directly regulating IL15 gene expression.