Progestins Regulate the Expression and Activity of the Forkhead Transcription Factor FOXO1 in Differentiating Human Endometrium

Soraya Labied, Takeshi Kajihara, Patrícia A. Madureira, Luca Fusi, Marius C. Jones, Jenny Higham, Rana Varshochi, Julia M. Francis, Georgia Zoumpoulidou, Abdelkader Essafi, Silvia Fernández de Mattos, Eric W.‐F. Lam, Jan J. Brosens
In: Molecular Endocrinology · 2005 · vol. 20(1) , pp. 35–44 · doi:10.1210/me.2005-0275 · PMID:16123151 · W1999084704
article OA: bronze CC0 ⤵ 19 in-corpus citations
📄 Open PDF View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

This study identifies FOXO1 as a progestin-regulated transcription factor that mediates apoptosis in differentiating human endometrial stromal cells upon progesterone withdrawal, linking decidualization to menstruation.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Abstract

Menstruation, or cyclic shedding of nonpregnant endometrial tissue with associated bleeding, occurs only in humans and a few other species. This breakdown of the endometrium in response to falling ovarian progesterone levels is a complex process, characterized by local leukocyte infiltration, expression and activation of matrix metalloproteinases, and apoptosis. Spontaneous decidualization (differentiation) of the stromal compartment precedes the cyclic shedding of the endometrium in various menstruating species but the mechanisms that link these processes are not understood. In this study, we identified FOXO1 as a key transcription factor responsible for mediating apoptosis of decidualized human endometrial stromal cells (HESCs) in response to progesterone withdrawal. We demonstrate that medroxyprogesterone acetate (MPA, a synthetic progestin) enhances the expression of FOXO1 in differentiating HESCs while simultaneously inducing cytoplasmic retention and inactivation of FOXO1. Withdrawal of MPA from decidualized HESCs results in rapid nuclear accumulation of FOXO1, increased BIM expression, a proapoptotic FOXO1 target gene, and cell death. Conversely, silencing of FOXO1 expression completely abolishes cell death induced by MPA withdrawal. In summary, the observation that differentiating HESCs become dependent on progesterone signaling for survival through induction and reversible inactivation of FOXO1 suggests a novel mechanism that links decidualization of the endometrium to menstruation.

My notes (saved in your browser only)

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (56)

Cited by (20)

Source provenance

openalex
last seen: 2026-06-10T17:14:06.276822+00:00
License: CC0 · commercial use OK