Glucose regulates the histone acetylation of gene promoters in decidualizing stromal cells. Issue 5 (May 2019)

• Record Type: Journal Article
• Authors: Jozaki, Kosuke; Tamura, Isao; Takagi, Haruka; Shirafuta, Yuichiro; Mihara, Yumiko; Shinagawa, Masahiro; Maekawa, Ryo; Taketani, Toshiaki; Asada, Hiromi; Sato, Shun; Tamura, Hiroshi; Sugino, Norihiro
• Is Part Of: Reproduction. Volume 157:Issue 5(2019)
• Page Start: 457
• Page End: 464
• Publication Date: 2019-05
• Subjects: Reproduction -- Periodicals; Reproduction -- Molecular aspects -- Periodicals; Reproduction -- Immunological aspects -- Periodicals; Reproduction -- Endocrine aspects -- Periodicals; Fertility -- Periodicals; Human reproduction -- Periodicals; 571.805
• DOI: 10.1530/REP-18-0393
• Languages: English
• ISSNs: 1470-1626

Abstract

Abstract : Decidualization stimuli activate the insulin signaling pathway and increase the glucose uptake in human endometrial stromal cells (ESCs). The inductions of prolactin ( PRL ) and IGF-binding protein-1 ( IGFBP1 ), specific markers of decidualization, were inhibited by incubating ESCs under low glucose concentrations. These results suggested that decidualization stimuli activate the insulin signaling pathway, which contributes to decidualization through the increase of glucose uptake. Here, we investigated the mechanisms by which glucose regulates decidualization. ESCs were incubated with cAMP to induce decidualization. We examined whether low glucose affects the expression levels of transcription factors that induce decidualization. Forkhead box O1 ( FOXO1 ) expression was significantly suppressed under low glucose conditions. Knockdown of FOXO1 by siRNA inhibited the expression levels of PRL and IGFBP1 during decidualization. Taken together, our results showed that low glucose inhibits decidualization by decreasing FOXO1 expression. We also examined the levels of histone H3K27 acetylation (H3K27ac), which is related to active transcription, of the promoter regions of FOXO1, PRL and IGFBP1 by ChIP assay. The H3K27ac levels of these promoter regions were increased by decidualization under normal glucose conditions, but not under low glucose conditions. Thus, our results show that glucose is indispensable for decidualization by activating the histone modification status of the promoters of PRL, IGFBP1 and FOXO1 .