# Endometriosis tissue shows reduced REST; Rest-knockout mice respond weakly to progesterone

- Published: 2026-11-13 05:59 UTC
- Section: Life & Health › Medicine
- Tags: endometriosis, REST transcription factor, progesterone resistance, Rest knockout mice, uterine-specific knockout, endometriotic lesions, subfertility, progesterone responsiveness
- URL: https://realtech.media/news/rt-bdcd0e25338ffdc368442ba1_endometriosis_tissue_shows/

**Nuclear REST was reduced in endometrium and lesions from patients with endometriosis. In mice, uterine Rest deletion caused subfertility and a weaker progesterone response.**

![Endometriosis tissue shows reduced REST; Rest-knockout mice respond weakly to progesterone](https://realtech.media/media/2026/11/fff27dd8051e21c2.jpg)
*International Gemini Observatory/NOIRLab/NSF/AURA, Wikimedia Commons, CC BY 4.0*

Researchers studied the role of the transcription factor RE1 silencing transcription factor (REST) in endometriosis using human tissue and a uterine-specific Rest conditional knockout mouse model, according to a study in Proceedings of the National Academy of Sciences. Immunohistochemical analysis of eutopic endometrium and ectopic lesions from patients with endometriosis showed significantly reduced nuclear REST expression compared with control endometrium [1]. Endometriosis is a steroid-dependent disease marked by progesterone (P4) resistance, subfertility or infertility, and pelvic pain, and the mechanisms of impaired P4 response in its tissue are not fully understood.

## Uterine Rest knockout in mice

Uterine-specific Rest knockout (Rest d/d) females showed progressive subfertility. Their uterine tissue had hyperestrogenic characteristics and a blunted response to P4 treatment [1]. Loss of Rest selectively altered the expression of P4-responsive genes associated with endometriosis pathology, while P4 receptor expression was preserved [1].

## Experimental endometriosis and lesion size

The authors then induced experimental endometriosis in mice. Females that developed endometriotic-like lesions from Rest-deficient donor tissue had significantly larger lesions than those given control tissue, and these lesions responded less to P4 treatment [1]. Mechanical sensitivity was modestly increased in mice receiving Rest-deficient tissue, whereas vaginal hyperalgesia was unaffected [1].

The authors conclude that loss of nuclear REST is a feature of endometriosis. They suggest that REST may contribute to altered P4 responsiveness and may be a potential therapeutic target [1]. The data on fertility, lesion growth and P4 response come from mouse models.

## Sources

1. [Proceedings of the National Academy of Sciences](https://doi.org/10.1073/pnas.2619014123)

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Source: RealTech, realtech.media — https://realtech.media/news/rt-bdcd0e25338ffdc368442ba1_endometriosis_tissue_shows/