Transcription factor ID1 is involved in decidualization of stromal cells: Implications in preeclampsia

Decidual stromal cells (DSC) from women with preeclampsia (PE) show defective decidualization upon in vitro treatment with cAMP. Decidualization is associated with a multitude of gene expression changes and is a prerequisite for embryo implantation. We reason that the process of decidualization involves a cascade of changes in transcriptional regulators. Our prior studies have found defective decidualization of PE-DSCs as reflected by low prolactin (PRL) levels and other decidualization markers. Transcription factor array analysis identified inhibitor of DNA binding (ID1) and FOXO1 as top differentially expressed genes during decidualization. Unlike ID1, FOXO1 involvement in decidualization has been established. We hypothesized that ID1 plays a major role in regulating stromal cell decidualization. Our data shows basal ID1 mRNA expression is significantly higher in PE DSCs. Cyclic AMP-mediated decidualization significantly upregulates ID1 mRNA expression in DSCs and siRNA-mediated knockdown of ID1 significantly interferes with decidualization as shown by a reduction in PRL and FOXO1 expression, and morphologic criteria. Thus ID1 may serve as a master regulator of stromal cell differentiation and defects in ID1 expression may affect decidualization as seen in PE-DSCs.