Involvement of the Increased SF-1 Expression Induced by DNA Hypomethylation through DNMTs in Endometrial Decidualization

Abstract Abnormal endometrial decidualization is closely related to embryo implantation failure and other pregnancy complications. Steroidogenic factor-1 (SF-1), which is also known as nuclear receptor subfamily 5 group A member 1, is a transcriptional activator that is involved in sexual differentiation and formation of the primary steroidogenic tissues. Its regulatory role in mouse and human endometrial decidualization remains unclear. In normal pregnant mice models, the expression of SF-1 was detected by immunohistochemistry and Western blot analysis. In normal pregnant mice, the expression of SF-1 at the implantation site is higher than that in the inter-implantation site. In the artificial decidualization in vivo and in vitro models, the expression of SF-1 increased with the deepening of decidualization. The high expression of SF-1 could promote the decidualization of endometrial stromal cells (ESCs). Based on the detection results of bisulfite sequencing PCR (BSP), the methylation of the CpG island in the SF-1 promoter region decreased after the decidualization of mouse endometrium. The interference of DNA methyltransferase (DNMT) expression promoted the expression of SF-1. The methylation inhibitor 5-aza resulted in the decrease in DNMTs, increase in SF-1 expression, and decidualization of ESCs. With the decidualization of the endometrium, the expression of SF-1 increased, whereas the DNA methylation of the SF-1 promoter decreased. The decrease in DNMTs resulted in increased SF-1 expression and promoted the decidualization of the endometrium. This study provides clues for the diagnosis and treatment of embryo implantation failure associated with abnormal decidualization.