Roles of endoplasmic reticulum stress in the pathophysiology of polycystic ovary syndrome
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women, affecting up to 15% of women in this group, and the most common cause of anovulatory infertility. Although its etiology remains unclear, recent research has revealed the critical role of endoplasmic...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-02-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1124405/full |
| _version_ | 1797924505567363072 |
|---|---|
| author | Hiroshi Koike Miyuki Harada Akari Kusamoto Zixin Xu Tsurugi Tanaka Nanoka Sakaguchi Chisato Kunitomi Jerilee M. K. Azhary Jerilee M. K. Azhary Nozomi Takahashi Yoko Urata Yutaka Osuga |
| author_facet | Hiroshi Koike Miyuki Harada Akari Kusamoto Zixin Xu Tsurugi Tanaka Nanoka Sakaguchi Chisato Kunitomi Jerilee M. K. Azhary Jerilee M. K. Azhary Nozomi Takahashi Yoko Urata Yutaka Osuga |
| author_sort | Hiroshi Koike |
| collection | DOAJ |
| description | Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women, affecting up to 15% of women in this group, and the most common cause of anovulatory infertility. Although its etiology remains unclear, recent research has revealed the critical role of endoplasmic reticulum (ER) stress in the pathophysiology of PCOS. ER stress is defined as a condition in which unfolded or misfolded proteins accumulate in the ER because of an imbalance in the demand for protein folding and the protein-folding capacity of the ER. ER stress results in the activation of several signal transduction cascades, collectively termed the unfolded protein response (UPR), which regulates various cellular activities. In principle, the UPR restores homeostasis and keeps the cell alive. However, if the ER stress cannot be resolved, it induces programmed cell death. ER stress has recently been recognized to play diverse roles in both physiological and pathological conditions of the ovary. In this review, we summarize current knowledge of the roles of ER stress in the pathogenesis of PCOS. ER stress pathways are activated in the ovaries of both a mouse model of PCOS and in humans, and local hyperandrogenism in the follicular microenvironment associated with PCOS is responsible for activating these. The activation of ER stress contributes to the pathophysiology of PCOS through multiple effects in granulosa cells. Finally, we discuss the potential for ER stress to serve as a novel therapeutic target for PCOS. |
| first_indexed | 2024-04-10T15:03:08Z |
| format | Article |
| id | doaj.art-78254a89a6ed46cda49a8549473da9a6 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-10T15:03:08Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-78254a89a6ed46cda49a8549473da9a62023-02-15T09:17:50ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-02-011410.3389/fendo.2023.11244051124405Roles of endoplasmic reticulum stress in the pathophysiology of polycystic ovary syndromeHiroshi Koike0Miyuki Harada1Akari Kusamoto2Zixin Xu3Tsurugi Tanaka4Nanoka Sakaguchi5Chisato Kunitomi6Jerilee M. K. Azhary7Jerilee M. K. Azhary8Nozomi Takahashi9Yoko Urata10Yutaka Osuga11Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Obstetrics and Gynaecology, Faculty of Medicine, University of Malaya, Kuala Lumpur, MalaysiaDepartment of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, JapanPolycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women, affecting up to 15% of women in this group, and the most common cause of anovulatory infertility. Although its etiology remains unclear, recent research has revealed the critical role of endoplasmic reticulum (ER) stress in the pathophysiology of PCOS. ER stress is defined as a condition in which unfolded or misfolded proteins accumulate in the ER because of an imbalance in the demand for protein folding and the protein-folding capacity of the ER. ER stress results in the activation of several signal transduction cascades, collectively termed the unfolded protein response (UPR), which regulates various cellular activities. In principle, the UPR restores homeostasis and keeps the cell alive. However, if the ER stress cannot be resolved, it induces programmed cell death. ER stress has recently been recognized to play diverse roles in both physiological and pathological conditions of the ovary. In this review, we summarize current knowledge of the roles of ER stress in the pathogenesis of PCOS. ER stress pathways are activated in the ovaries of both a mouse model of PCOS and in humans, and local hyperandrogenism in the follicular microenvironment associated with PCOS is responsible for activating these. The activation of ER stress contributes to the pathophysiology of PCOS through multiple effects in granulosa cells. Finally, we discuss the potential for ER stress to serve as a novel therapeutic target for PCOS.https://www.frontiersin.org/articles/10.3389/fendo.2023.1124405/fullendoplasmic reticulum stress (ER stress)pathophysiologypolycystic ovary syndrome (PCOS)unfolded protein response (UPR)follicular microenvironmentovary |
| spellingShingle | Hiroshi Koike Miyuki Harada Akari Kusamoto Zixin Xu Tsurugi Tanaka Nanoka Sakaguchi Chisato Kunitomi Jerilee M. K. Azhary Jerilee M. K. Azhary Nozomi Takahashi Yoko Urata Yutaka Osuga Roles of endoplasmic reticulum stress in the pathophysiology of polycystic ovary syndrome Frontiers in Endocrinology endoplasmic reticulum stress (ER stress) pathophysiology polycystic ovary syndrome (PCOS) unfolded protein response (UPR) follicular microenvironment ovary |
| title | Roles of endoplasmic reticulum stress in the pathophysiology of polycystic ovary syndrome |
| title_full | Roles of endoplasmic reticulum stress in the pathophysiology of polycystic ovary syndrome |
| title_fullStr | Roles of endoplasmic reticulum stress in the pathophysiology of polycystic ovary syndrome |
| title_full_unstemmed | Roles of endoplasmic reticulum stress in the pathophysiology of polycystic ovary syndrome |
| title_short | Roles of endoplasmic reticulum stress in the pathophysiology of polycystic ovary syndrome |
| title_sort | roles of endoplasmic reticulum stress in the pathophysiology of polycystic ovary syndrome |
| topic | endoplasmic reticulum stress (ER stress) pathophysiology polycystic ovary syndrome (PCOS) unfolded protein response (UPR) follicular microenvironment ovary |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1124405/full |
| work_keys_str_mv | AT hiroshikoike rolesofendoplasmicreticulumstressinthepathophysiologyofpolycysticovarysyndrome AT miyukiharada rolesofendoplasmicreticulumstressinthepathophysiologyofpolycysticovarysyndrome AT akarikusamoto rolesofendoplasmicreticulumstressinthepathophysiologyofpolycysticovarysyndrome AT zixinxu rolesofendoplasmicreticulumstressinthepathophysiologyofpolycysticovarysyndrome AT tsurugitanaka rolesofendoplasmicreticulumstressinthepathophysiologyofpolycysticovarysyndrome AT nanokasakaguchi rolesofendoplasmicreticulumstressinthepathophysiologyofpolycysticovarysyndrome AT chisatokunitomi rolesofendoplasmicreticulumstressinthepathophysiologyofpolycysticovarysyndrome AT jerileemkazhary rolesofendoplasmicreticulumstressinthepathophysiologyofpolycysticovarysyndrome AT jerileemkazhary rolesofendoplasmicreticulumstressinthepathophysiologyofpolycysticovarysyndrome AT nozomitakahashi rolesofendoplasmicreticulumstressinthepathophysiologyofpolycysticovarysyndrome AT yokourata rolesofendoplasmicreticulumstressinthepathophysiologyofpolycysticovarysyndrome AT yutakaosuga rolesofendoplasmicreticulumstressinthepathophysiologyofpolycysticovarysyndrome |