Endometriosis Knowledgebase


A repository for genes associated with endometriosis

Results


PMID 25546156
Gene Name HEY1
Condition Endometriosis
Association Associated
Age 18–49 yrs
Sex Female
Infertility type Female infertility
Associated genes NOTCH1, NOTCH4, JAGGED2, DLL4, HES5, HEY1
Other associated phenotypes Endometriosis
Decreased Notch pathway signaling in the endometrium of women with endometriosis impairs decidualization.

J Clin Endocrinol Metab. 2015 Mar;100(3):E433-42. doi: 10.1210/jc.2014-3720. Epub

Su, Ren-Wei| Strug, Michael R| Joshi, Niraj R| Jeong, Jae-Wook| Miele, Lucio| Lessey, Bruce A| Young, Steve L| Fazleabas, Asgerally T

Department of Obstetrics, Gynecology and Reproductive Biology (R.-W.S., M.R.S., N.R.J., J.-W.J., A.T.F.), Michigan State University, Grand Rapids, Michigan 49503; Cancer Institute (L.M.), Louisiana State University Health Sciences Center and Stanley S.

CONTEXT: Endometriosis is a common gynecological disease affecting one in 10 women of reproductive age and is a major cause of pelvic pain and impaired fertility. Endometrial stromal cells of women with endometriosis exhibit a reduced response to in vitro decidualization. NOTCH1 is critical for decidualization of both mouse and human uterine stromal cells. OBJECTIVE: This study aimed to determine whether decidualization failure in women with endometriosis is a consequence of impaired Notch signaling. SETTING AND DESIGN: We investigated expression levels of Notch signaling components in the endometrium of women and baboons with or without endometriosis. We identified NOTCH1-regulated genes during decidualization of human uterine fibroblast (HuF) cells by microarray and quantified their expression levels in in vitro-decidualized endometrial stromal cells isolated from women with or without endometriosis. RESULTS: Notch signaling receptors NOTCH1 and NOTCH4, ligands JAGGED2 and DLL4, as well as direct target genes HES5 and HEY1 were decreased in the eutopic endometrium of women and baboons with endometriosis. Notch signaling was decreased in stromal cells isolated from women with endometriosis, which was associated with impaired in vitro decidualization. Genes that were down-regulated by NOTCH1 silencing in decidualized HuF cells were also decreased in decidualized endometrial stromal cells of women with endometriosis. FOXO1 acts as a downstream target of Notch signaling and endometriosis is associated with decreased expression of NOTCH1-regulated, FOXO1-responsive genes during decidualization. CONCLUSIONS: Decreased Notch signaling is associated with endometriosis and contributes to impaired decidualization through the down-regulation of FOXO1.

Mesh Terms: Animals| Decidua/*physiology| Down-Regulation| Embryo Implantation/*physiology| Endometriosis/genetics/metabolism/*pathology| Endometrium/*metabolism/pathology| Female| Gene Expression Profiling| HEK293 Cells| Humans| Microarray Analysis| Monke