Decreased Notch Pathway Signaling in the Endometrium of Women With Endometriosis Impairs Decidualization

Ren‐Wei Su, Ren-Wei Su, Michael Strug, Michael R Strug, Niraj Joshi, Niraj R Joshi, Jae-Wook Jeong, Jae‐Wook Jeong, Lucio Miele, Bruce A Lessey, Steven L. Young, Steve L Young, Asgerally T Fazleabas
The Journal of clinical endocrinology and metabolism · 2014 · vol. 100(3) , pp. E433–E442 · doi:10.1210/jc.2014-3720 · PMID:25546156 · PMC4333047 · W2123606632
article OA: bronze CC0 ⤵ 65 in-corpus citations
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⚙ AI-generated summary by claude@2026-06, 2026-06-09 ⓘ

Women with endometriosis exhibit decreased Notch signaling in the endometrium, which impairs decidualization by down-regulating FOXO1 and its responsive genes.

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Abstract

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.

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Condition tags

endometriosis

MeSH descriptors

Decidua Embryo Implantation Endometriosis Endometrium Peritoneal Diseases Receptor, Notch1 Animals Decidua Down-Regulation Embryo Implantation Endometriosis Endometriosis Endometriosis Endometrium Endometrium Female Gene Expression Profiling HEK293 Cells Humans Microarray Analysis

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