Endometrial Expression of Steroidogenic Factor 1 Promotes Cystic Glandular Morphogenesis

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Endometrial SF1 expression in mice promotes enlarged uterine glands, alters steroid hormone responsiveness, and enhances ectopic lesion growth, implicating SF1 in abnormal gland morphogenesis and inflammation.

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Abstract

Epigenetic silencing of steroidogenic factor 1 (SF1) is lost in endometriosis, potentially contributing to de novo local steroidogenesis favoring inflammation and growth of ectopic endometrial tissue. In this study, we examine the impact of SF1 expression in the eutopic uterus by a novel mouse model that conditionally expresses SF1 in endometrium. In vivo SF1 expression promoted the development of enlarged endometrial glands and attenuated estrogen and progesterone responsiveness. Endometriosis induction by autotransplantation of uterine tissue to the mesenteric membrane resulted in the increase in size of ectopic lesions from SF1-expressing mice. By integrating the SF1-dependent transcriptome with the whole genome binding profile of SF1, we identified uterine-specific SF1-regulated genes involved in Wingless and Progesterone receptor-Hedgehog-Chicken ovalbumin upstream promoter transcription factor II signaling for gland development and epithelium-stroma interaction, respectively. The present results indicate that SF1 directly contributes to the abnormal uterine gland morphogenesis, an inhibition of steroid hormone signaling and activation of an immune response, in addition to previously postulated estrogen production.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometrium Morphogenesis RNA Splicing Factors Urogenital Abnormalities Uterus Animals COUP Transcription Factor II COUP Transcription Factor II Endometriosis Endometrium Estrogens Estrogens Female Mice Morphogenesis Progesterone Progesterone Receptors, Progesterone Receptors, Progesterone

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europepmc
last seen: 2026-06-12T06:13:51.797165+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-05-13T22:21:07.355239+00:00
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