title: Endometrial Expression of Steroidogenic Factor 1 Promotes Cystic Glandular Morphogenesis.
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.
authors.affiliation: 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.
authors.forename: Yasmin M
authors.initials: YM
authors.lastname: Vasquez
authors.affiliation: 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.
authors.forename: San-Pin
authors.initials: SP
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Anderson
authors.affiliation: 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.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Hawkins
authors.affiliation: 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.
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Creighton
authors.affiliation: 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.
authors.forename: Madhumita
authors.initials: M
authors.lastname: Ray
authors.affiliation: 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.
authors.forename: Sophia Y
authors.initials: SY
authors.lastname: Tsai
authors.affiliation: 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.
authors.forename: Ming-Jer
authors.initials: MJ
authors.lastname: Tsai
authors.affiliation: 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.
authors.forename: John P
authors.initials: JP
authors.lastname: Lydon
authors.affiliation: 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.
authors.forename: Francesco J
authors.initials: FJ
authors.lastname: DeMayo
mesh_terms: D000818:Animals; D051837:COUP Transcription Factor II / Q000378:metabolism; D004715:Endometriosis / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D051379:Mice; D009024:Morphogenesis / Q000502:physiology*; D011374:Progesterone / Q000378:metabolism; D000072260:RNA Splicing Factors / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D017154:Stromal Cells / Q000378:metabolism; D059467:Transcriptome / Q000502:physiology; D014564:Urogenital Abnormalities / Q000378:metabolism*; D014599:Uterus / Q000002:abnormalities* / Q000378:metabolism
chemical_list: D051837:COUP Transcription Factor II; D004967:Estrogens; D000072260:RNA Splicing Factors; D011980:Receptors, Progesterone; C491514:Sf1 protein, mouse; D011374:Progesterone