Open AccessEndometrial Expression of Steroidogenic Factor 1 Promotes Cystic Glandular Morphogenesis
Author(s) -
Yasmin M. Vasquez,
SanPin Wu,
Matthew L. Anderson,
Shan M. Hawkins,
Chad J. Creighton,
Madhumita Ray,
Sophia Y. Tsai,
MingJer Tsai,
John P. Lydon,
Francesco J. DeMayo
Publication year - 2016
Publication title -
molecular endocrinology
Language(s) - English
Resource type - Journals
eISSN - 1944-9917
pISSN - 0888-8809
DOI - 10.1210/me.2015-1215
Subject(s) - biology , steroidogenic factor 1 , indian hedgehog , endocrinology , medicine , ectopic expression , decidualization , estrogen receptor , progesterone receptor , endometrium , hedgehog , transcription factor , nuclear receptor , microbiology and biotechnology , signal transduction , cell culture , gene , genetics , cancer , breast cancer
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.