HBP1 facilitates PGR transcriptional activity and IGFBP1 expression conducive to human endometrial decidualization

Decidualization of human endometrial stromal cells (HESCs) is one of the critical steps in the establishment of human pregnancy. HESCs decidualization provides a suitable microenvironment for embryo implantation and pregnancy maintenance. Nevertheless, little is known about the molecular mechanisms underlying human decidualization. In this study, we identified HBP1 as a key player in the decidualization of HESCs. Knockdown of HBP1 significantly reduced the mRNA and protein expression levels of decidualization markers IGFBP1 and FOXO1. Although PGR expression showed no significant change, the expression levels of PGR-regulated target molecules were decreased. Furthermore, ChIP-Seq and RNA-seq analyses revealed that HBP1 directly transcriptionally regulates IGFBP1 expression. Additionally, overexpression of HBP1 promoted the enrichment of histone H3K4me3 at the promoter regions of PGR and its target molecules FKBP5, FOSL2, and FKBP4, which indicated that HBP1 enhances PGR transcriptional activity, thereby playing a pivotal role in endometrial decidualization. Clinical specimen analysis further confirmed that the expression of HBP1 and PGR target molecules was significantly downregulated in the endometrium of patients with recurrent implantation failure. In conclusion, this study demonstrated that HBP1 played a crucial regulatory role in endometrial decidualization by directly transcriptionally regulating the decidualization marker IGFBP1 and enhancing PGR transcriptional activity through H3K4me3 modification.