Endometrial expression of steroidogenic factor 1 promotes cystic glandular morphogenesis

Yasmin M. Vasquez, San Pin Wu, Matthew L. Anderson, Shannon Hawkins, Chad J. Creighton, Madhumita Ray, Sophia Y. Tsai, Ming Jer Tsai, John P. Lydon, Francesco J. DeMayo

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)518-532
Number of pages15
JournalMolecular Endocrinology
Volume30
Issue number5
DOIs
StatePublished - May 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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    Vasquez, Y. M., Wu, S. P., Anderson, M. L., Hawkins, S., Creighton, C. J., Ray, M., Tsai, S. Y., Tsai, M. J., Lydon, J. P., & DeMayo, F. J. (2016). Endometrial expression of steroidogenic factor 1 promotes cystic glandular morphogenesis. Molecular Endocrinology, 30(5), 518-532. https://doi.org/10.1210/me.2015-1215