title: A potential role of endoplasmic reticulum stress in development of ovarian hyperstimulation syndrome.
abstract: Vascular endothelial growth factor A (VEGFA) is crucial for ovarian angiogenesis, but its excess production induces ovarian hyperstimulation syndrome (OHSS). The aim of this study was to determine whether endoplasmic reticulum (ER) stress regulates VEGFA expression in granulosa cells, and whether its activation is involved in OHSS development. The expression of the spliced form of X-box-binding protein 1 [XBP1(S)], induced by ER stress, in cumulus cells from OHSS patients was higher than that in cumulus cells from non-OHSS patients. The ER stress inducer tunicamycin increased human chorionic gonadotropin-induced VEGFA production in human granulosa cells through the induction of XBP1(S), and pretreatment with the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) abrogated the effect of tunicamycin. In OHSS model rats, TUDCA administration prevented the OHSS development, reducing ovarian VEGFA production. Our findings suggest ER stress upregulates hCG-induced VEGFA production in granulosa cells, indicating that ER stress might be involved in OHSS development.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo, 113-8655, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo, 113-8655, Japan. Electronic address: haradam-tky@umin.ac.jp.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Harada
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo, 113-8655, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hirota
authors.affiliation: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116044, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yoshino
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo, 113-8655, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Urata
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo, 113-8655, Japan.
authors.forename: Gentaro
authors.initials: G
authors.lastname: Izumi
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo, 113-8655, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Takamura
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo, 113-8655, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hirata
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo, 113-8655, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Koga
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo, 113-8655, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Wada-Hiraike
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo, 113-8655, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo, 113-8655, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Osuga
mesh_terms: D000328:Adult; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000008:administration & dosage / Q000494:pharmacology; D054885:Cumulus Cells / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005260:Female; D006801:Humans; D008184:Luteal Cells / Q000187:drug effects / Q000378:metabolism; D016471:Ovarian Hyperstimulation Syndrome / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D000071717:X-Box Binding Protein 1 / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; D014415:Tunicamycin; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine
keywords: Endoplasmic reticulum stress; Ovarian hyperstimulation syndrome; Ovary; Unfolded protein response; Vascular endothelial growth factor A