Activation of Endoplasmic Reticulum Stress in Granulosa Cells from Patients with Polycystic Ovary Syndrome Contributes to Ovarian Fibrosis

Abstract Recent studies report the involvement of intra-ovarian factors, such as inflammation and oxidative stress, in the pathophysiology of polycystic ovary syndrome (PCOS), the most common endocrine disorder of reproductive age women. Endoplasmic reticulum (ER) stress is a local factor that affec...

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Autores principales:	Nozomi Takahashi, Miyuki Harada, Yasushi Hirota, Emi Nose, Jerilee MK Azhary, Hiroshi Koike, Chisato Kunitomi, Osamu Yoshino, Gentaro Izumi, Tetsuya Hirata, Kaori Koga, Osamu Wada-Hiraike, R. Jeffrey Chang, Shunichi Shimasaki, Tomoyuki Fujii, Yutaka Osuga
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a896312441f14824ba86b094670a2d29
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spelling	oai:doaj.org-article:a896312441f14824ba86b094670a2d292021-12-02T15:05:32ZActivation of Endoplasmic Reticulum Stress in Granulosa Cells from Patients with Polycystic Ovary Syndrome Contributes to Ovarian Fibrosis10.1038/s41598-017-11252-72045-2322https://doaj.org/article/a896312441f14824ba86b094670a2d292017-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-11252-7https://doaj.org/toc/2045-2322Abstract Recent studies report the involvement of intra-ovarian factors, such as inflammation and oxidative stress, in the pathophysiology of polycystic ovary syndrome (PCOS), the most common endocrine disorder of reproductive age women. Endoplasmic reticulum (ER) stress is a local factor that affects various cellular events during a broad spectrum of physiological and pathological conditions. It may also be an important determinant of pro-fibrotic remodeling during tissue fibrosis. In the present study, we showed that ER stress was activated in granulosa cells of PCOS patients as well as in a well-established PCOS mouse model. Pharmacological inducers of ER stress, tunicamycin and thapsigargin, were found to increase the expression of pro-fibrotic growth factors, including transforming growth factor (TGF)-β1, in human granulosa cells, and their expression also increased in granulosa cells of PCOS patients. By contrast, treatment of PCOS mice with an ER stress inhibitor, tauroursodeoxycholic acid or BGP-15, decreased interstitial fibrosis and collagen deposition in ovaries, accompanied by a reduction in TGF-β1 expression in granulosa cells. These findings suggest that ER stress in granulosa cells of women with PCOS contributes to the induction of pro-fibrotic growth factors during ovarian fibrosis, and that ER stress may serve as a therapeutic target in PCOS.Nozomi TakahashiMiyuki HaradaYasushi HirotaEmi NoseJerilee MK AzharyHiroshi KoikeChisato KunitomiOsamu YoshinoGentaro IzumiTetsuya HirataKaori KogaOsamu Wada-HiraikeR. Jeffrey ChangShunichi ShimasakiTomoyuki FujiiYutaka OsugaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nozomi Takahashi Miyuki Harada Yasushi Hirota Emi Nose Jerilee MK Azhary Hiroshi Koike Chisato Kunitomi Osamu Yoshino Gentaro Izumi Tetsuya Hirata Kaori Koga Osamu Wada-Hiraike R. Jeffrey Chang Shunichi Shimasaki Tomoyuki Fujii Yutaka Osuga Activation of Endoplasmic Reticulum Stress in Granulosa Cells from Patients with Polycystic Ovary Syndrome Contributes to Ovarian Fibrosis
description	Abstract Recent studies report the involvement of intra-ovarian factors, such as inflammation and oxidative stress, in the pathophysiology of polycystic ovary syndrome (PCOS), the most common endocrine disorder of reproductive age women. Endoplasmic reticulum (ER) stress is a local factor that affects various cellular events during a broad spectrum of physiological and pathological conditions. It may also be an important determinant of pro-fibrotic remodeling during tissue fibrosis. In the present study, we showed that ER stress was activated in granulosa cells of PCOS patients as well as in a well-established PCOS mouse model. Pharmacological inducers of ER stress, tunicamycin and thapsigargin, were found to increase the expression of pro-fibrotic growth factors, including transforming growth factor (TGF)-β1, in human granulosa cells, and their expression also increased in granulosa cells of PCOS patients. By contrast, treatment of PCOS mice with an ER stress inhibitor, tauroursodeoxycholic acid or BGP-15, decreased interstitial fibrosis and collagen deposition in ovaries, accompanied by a reduction in TGF-β1 expression in granulosa cells. These findings suggest that ER stress in granulosa cells of women with PCOS contributes to the induction of pro-fibrotic growth factors during ovarian fibrosis, and that ER stress may serve as a therapeutic target in PCOS.
format	article
author	Nozomi Takahashi Miyuki Harada Yasushi Hirota Emi Nose Jerilee MK Azhary Hiroshi Koike Chisato Kunitomi Osamu Yoshino Gentaro Izumi Tetsuya Hirata Kaori Koga Osamu Wada-Hiraike R. Jeffrey Chang Shunichi Shimasaki Tomoyuki Fujii Yutaka Osuga
author_facet	Nozomi Takahashi Miyuki Harada Yasushi Hirota Emi Nose Jerilee MK Azhary Hiroshi Koike Chisato Kunitomi Osamu Yoshino Gentaro Izumi Tetsuya Hirata Kaori Koga Osamu Wada-Hiraike R. Jeffrey Chang Shunichi Shimasaki Tomoyuki Fujii Yutaka Osuga
author_sort	Nozomi Takahashi
title	Activation of Endoplasmic Reticulum Stress in Granulosa Cells from Patients with Polycystic Ovary Syndrome Contributes to Ovarian Fibrosis
title_short	Activation of Endoplasmic Reticulum Stress in Granulosa Cells from Patients with Polycystic Ovary Syndrome Contributes to Ovarian Fibrosis
title_full	Activation of Endoplasmic Reticulum Stress in Granulosa Cells from Patients with Polycystic Ovary Syndrome Contributes to Ovarian Fibrosis
title_fullStr	Activation of Endoplasmic Reticulum Stress in Granulosa Cells from Patients with Polycystic Ovary Syndrome Contributes to Ovarian Fibrosis
title_full_unstemmed	Activation of Endoplasmic Reticulum Stress in Granulosa Cells from Patients with Polycystic Ovary Syndrome Contributes to Ovarian Fibrosis
title_sort	activation of endoplasmic reticulum stress in granulosa cells from patients with polycystic ovary syndrome contributes to ovarian fibrosis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a896312441f14824ba86b094670a2d29
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Activation of Endoplasmic Reticulum Stress in Granulosa Cells from Patients with Polycystic Ovary Syndrome Contributes to Ovarian Fibrosis

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