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Excessive oxidative stress in cumulus granulosa cells induced cell senescence contributes to endometriosis-associated infertility.
Redox Biol 2020; 30:101431RB

Abstract

Endometriosis an important cause of female infertility and seriously impact physical and psychological health of patients. Endometriosis is now considered to be a public health problem that deserves in-depth investigation, especially the etiopathogenesis of endometriosis-associated infertility. We aimed to illuminate the etiopathogenesis of endometriosis-associated infertility that involve excessive oxidative stress (OS) induced pathological changes of ovary cumulus granulosa cell (GCs). Senescence-associated β-galactosidase (SA β-gal) activity in GCs from endometriosis patients, soluble isoform of advanced glycation end products receptor (sRAGE) expression in follicular fluid from endometriosis patients and differentially expressed senescence-associated secretory phenotype factors (IL-1β, MMP-9, KGF and FGF basic protein) are all useful indexes to evaluate oocyte retrieval number and mature oocyte number. RNA-sequencing and bioinformatics analysis indicated senescent phenotype of endometriosis GCs and aggravated endoplasmic reticulum (ER) stress in endometriosis GCs. Targeting ER stress significantly alleviated OS-induced GCs senescence as well as mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) reduction in GCs. Moreover, melatonin administration rescued OS-enhanced ER stress, cellular senescence, and MMP and ATP abnormities of endometriosis GCs in vitro and in vivo. In conclusion, our results indicated excessive reactive oxygen species induces senescence of endometriosis GCs via arouse ER stress, which finally contributes to endometriosis-associated infertility, and melatonin may represent a novel adjuvant therapy strategy for endometriosis-associated infertility.

Authors+Show Affiliations

Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China.Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China.Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China.Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China.Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China.Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China.Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China.Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China.Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China.Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China.Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China.Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China. Electronic address: zhangsongying@zju.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31972508

Citation

Lin, Xiang, et al. "Excessive Oxidative Stress in Cumulus Granulosa Cells Induced Cell Senescence Contributes to Endometriosis-associated Infertility." Redox Biology, vol. 30, 2020, p. 101431.
Lin X, Dai Y, Tong X, et al. Excessive oxidative stress in cumulus granulosa cells induced cell senescence contributes to endometriosis-associated infertility. Redox Biol. 2020;30:101431.
Lin, X., Dai, Y., Tong, X., Xu, W., Huang, Q., Jin, X., ... Zhang, S. (2020). Excessive oxidative stress in cumulus granulosa cells induced cell senescence contributes to endometriosis-associated infertility. Redox Biology, 30, p. 101431. doi:10.1016/j.redox.2020.101431.
Lin X, et al. Excessive Oxidative Stress in Cumulus Granulosa Cells Induced Cell Senescence Contributes to Endometriosis-associated Infertility. Redox Biol. 2020 Jan 12;30:101431. PubMed PMID: 31972508.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Excessive oxidative stress in cumulus granulosa cells induced cell senescence contributes to endometriosis-associated infertility. AU - Lin,Xiang, AU - Dai,Yongdong, AU - Tong,Xiaomei, AU - Xu,Wenzhi, AU - Huang,Qianmeng, AU - Jin,Xiaoying, AU - Li,Chao, AU - Zhou,Feng, AU - Zhou,Hanjin, AU - Lin,Xiaona, AU - Huang,Dong, AU - Zhang,Songying, Y1 - 2020/01/12/ PY - 2019/12/12/received PY - 2020/01/06/revised PY - 2020/01/10/accepted PY - 2020/1/24/pubmed PY - 2020/1/24/medline PY - 2020/1/24/entrez KW - Cumulus granulosa cell KW - Endometriosis KW - Endoplasmic reticulum stress KW - Infertility KW - Oxidative stress KW - Senescence SP - 101431 EP - 101431 JF - Redox biology JO - Redox Biol VL - 30 N2 - Endometriosis an important cause of female infertility and seriously impact physical and psychological health of patients. Endometriosis is now considered to be a public health problem that deserves in-depth investigation, especially the etiopathogenesis of endometriosis-associated infertility. We aimed to illuminate the etiopathogenesis of endometriosis-associated infertility that involve excessive oxidative stress (OS) induced pathological changes of ovary cumulus granulosa cell (GCs). Senescence-associated β-galactosidase (SA β-gal) activity in GCs from endometriosis patients, soluble isoform of advanced glycation end products receptor (sRAGE) expression in follicular fluid from endometriosis patients and differentially expressed senescence-associated secretory phenotype factors (IL-1β, MMP-9, KGF and FGF basic protein) are all useful indexes to evaluate oocyte retrieval number and mature oocyte number. RNA-sequencing and bioinformatics analysis indicated senescent phenotype of endometriosis GCs and aggravated endoplasmic reticulum (ER) stress in endometriosis GCs. Targeting ER stress significantly alleviated OS-induced GCs senescence as well as mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) reduction in GCs. Moreover, melatonin administration rescued OS-enhanced ER stress, cellular senescence, and MMP and ATP abnormities of endometriosis GCs in vitro and in vivo. In conclusion, our results indicated excessive reactive oxygen species induces senescence of endometriosis GCs via arouse ER stress, which finally contributes to endometriosis-associated infertility, and melatonin may represent a novel adjuvant therapy strategy for endometriosis-associated infertility. SN - 2213-2317 UR - https://www.unboundmedicine.com/medline/citation/31972508/Excessive_oxidative_stress_in_cumulus_granulosa_cells_induced_cell_senescence_contributes_to_endometriosis-associated_infertility L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-2317(19)31499-5 DB - PRIME DP - Unbound Medicine ER -