title: Genistein promotes DNA demethylation of the steroidogenic factor 1 (SF-1) promoter in endometrial stromal cells.
abstract: It has recently been demonstrated that genistein (GEN), a phytoestrogen in soy products, is an epigenetic modulator in various types of cells; but its effect on endometrium has not yet been determined. We investigated the effects of GEN on mouse uterine cells, in vivo and in vitro. Oral administration of GEN for 1 week induced mild proliferation of the endometrium in ovariectomized (OVX) mice, which was accompanied by the induction of steroidogenic factor 1 (SF-1) gene expression. GEN administration induced demethylation of multiple CpG sites in the SF-1 promoter; these sites are extensively methylated and thus silenced in normal endometrium. The GEN-mediated promoter demethylation occurred predominantly on the luminal side, as opposed to myometrium side, indicating that the epigenetic change was mainly shown in regenerated cells. Primary cultures of endometrial stromal cell colonies were screened for GEN-mediated alterations of DNA methylation by a high-resolution melting (HRM) method. One out of 20 colony-forming cell clones showed GEN-induced demethylation of SF-1. This clone exhibited a high proliferation capacity with continuous colony formation activity through multiple serial clonings. We propose that only a portion of endometrial cells are capable of receiving epigenetic modulation by GEN.
authors.affiliation: Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062, Japan. hmatsukura.epi@mri.tmd.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsukura
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Aisaki
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Igarashi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsushima
authors.forename: Jun
authors.initials: J
authors.lastname: Kanno
authors.forename: Masaaki
authors.initials: M
authors.lastname: Muramatsu
authors.forename: Katsuko
authors.initials: K
authors.lastname: Sudo
authors.forename: Noriko
authors.initials: N
authors.lastname: Sato
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019175:DNA Methylation / Q000187:drug effects*; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic / Q000187:drug effects; D054339:Steroidogenic Factor 1 / Q000235:genetics*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism
chemical_list: D054339:Steroidogenic Factor 1; C515058:steroidogenic factor 1, mouse; D019833:Genistein