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

作者：Takahashi Nozomi; Harada Miyuki^*; Hirota Yasushi; Nose Emi; Azhary Jerilee Mk; Koike Hiroshi; Kunitomi Chisato; Yoshino Osamu; Izumi Gentaro; Hirata Tetsuya; Koga Kaori; Wada Hiraike Osamu; Chang R Jeffrey; Shimasaki Shunichi; Fujii Tomoyuki; Osuga Yutaka

来源：Scientific Reports, 2017, 7(1): 10824.

DOI：10.1038/s41598-017-11252-7

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)-beta 1, 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-beta 1 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.

• 出版日期2017-9-7