RE1 silencing transcription factor is reduced in endometriosis, and uterine deletion in mice alters progesterone responsiveness.

Nuclear RE1 silencing transcription factor (REST) expression is significantly reduced in eutopic endometrium and ectopic lesions from patients with endometriosis.

• Why it matters: Endometriosis involves progesterone (P4) resistance, subfertility/infertility, and pain, but the molecular basis for impaired P4 responsiveness in affected tissue is not fully defined.
• What they did: The study compared REST nuclear staining in human eutopic and ectopic samples, then used uterine-specific Rest conditional knockout mice to test P4 responsiveness and gene expression, including an experimental endometriosis induction with Rest-deficient donor tissue.
• The result: Rest d/d females showed progressive subfertility, hyperestrogenic uterine features, and blunted P4 responsiveness with altered P4-responsive gene expression despite preserved P4 receptor expression; lesions induced with Rest-deficient tissue were significantly larger and less responsive to P4.

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