title: H19 lncRNA alters stromal cell growth via IGF signaling in the endometrium of women with endometriosis.
abstract: Endometriosis affects approximately 15% of reproductive aged women and is associated with chronic pelvic pain and infertility. However, the molecular mechanisms by which endometriosis impacts fertility are poorly understood. The developmentally regulated, imprinted H19 long noncoding RNA (lncRNA) functions to reduce the bioavailability of microRNA let-7 by acting as a molecular sponge. Here we report that H19 expression is significantly decreased in the eutopic endometrium of women with endometriosis as compared to normal controls. We show that decreased H19 increases let-7 activity, which in turn inhibits Igf1r expression at the post-transcriptional level, thereby contributing to reduced proliferation of endometrial stromal cells. We propose that perturbation of this newly identified H19/Let-7/IGF1R regulatory pathway may contribute to impaired endometrial preparation and receptivity for pregnancy in women with endometriosis. Our finding represents the first example of a lncRNA-based mechanism in endometriosis and its associated infertility, thus holding potential in the development of novel therapeutics for women with endometriosis and infertility.
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Ghazal
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Bern, Bern, Switzerland.
authors.forename: Brett
authors.initials: B
authors.lastname: McKinnon
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA Department of Surgical Oncology, Affiliated Sir Run Run Shaw Hospital Zhejiang University School of Medicine, Hangzhou Zhejiang, China.
authors.forename: Jichun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA Department of Obstetrics and Gynecology, University Hospital Bern, Bern, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Mueller
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA Department of Oral and Maxillofacial Surgery, State Key Laboratory of Oral Diseases West China Hospital of Stomatology Sichuan University, Chengdu Sichuan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Men
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA Obstetrics and Gynecology Department, Tangshan Gongren Hospital, Tangshan Hebei, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Bern, Bern, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Mueller
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Clare
authors.initials: C
authors.lastname: Flannery
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA yingqun.huang@yale.edu hugh.taylor@yale.edu.
authors.forename: Yingqun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA yingqun.huang@yale.edu hugh.taylor@yale.edu.
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Taylor
mesh_terms: D049109:Cell Proliferation; D004715:Endometriosis / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction; D013002:Somatomedins / Q000378:metabolism*; D017154:Stromal Cells / Q000502:physiology*
chemical_list: C094335:H19 long non-coding RNA; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D013002:Somatomedins; C487931:mirnlet7 microRNA, human; D017526:Receptor, IGF Type 1
keywords: H19; IGF; endometrium; let‐7; long noncoding RNA