Vasquez Yasmin M, Wu San-Pin, Anderson Matthew L, Hawkins Shannon M, Creighton Chad J, Ray Madhumita, Tsai Sophia Y, Tsai Ming-Jer, Lydon John P, DeMayo Francesco J
Department of Molecular and Cellular Biology (Y.M.V., S.Y.T., M.-J.T., J.P.L., F.J.D.), Baylor College of Medicine, Houston, Texas 77030; Department of Obstetrics and Gynecology (M.L.A., S.M.H.), Baylor College of Medicine, Houston, Texas 77030; Dan L. Duncan Cancer Center (M.L.A., C.J.C.), Division of Biostatistics, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030; and Pregnancy and Female Reproduction Group (S.-P.W., M.R., M.J.D.), National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Mol Endocrinol. 2016 May;30(5):518-32. doi: 10.1210/me.2015-1215. Epub 2016 Mar 28.
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.
在子宫内膜异位症中，类固醇生成因子1（SF1）的表观遗传沉默消失，这可能导致异位子宫内膜组织从头开始局部类固醇生成，从而促进炎症和生长。在本研究中，我们通过一种在子宫内膜中条件性表达SF1的新型小鼠模型，研究了SF1在正常子宫中的表达影响。体内SF1表达促进了子宫内膜腺体的增大，并减弱了雌激素和孕激素反应性。将子宫组织自体移植到肠系膜膜诱导子宫内膜异位症，导致来自表达SF1小鼠的异位病变大小增加。通过将SF1依赖性转录组与SF1的全基因组结合谱整合，我们鉴定出子宫特异性的SF1调节基因，分别参与无翅和孕激素受体-刺猬信号通路-鸡卵清蛋白上游启动子转录因子II信号通路，以促进腺体发育和上皮-基质相互作用。目前的结果表明，除了先前推测的雌激素产生外，SF1还直接导致子宫腺体形态异常、类固醇激素信号传导抑制和免疫反应激活。
