Elsevier

Redox Biology

Volume 30, February 2020, 101431
Redox Biology

Research Paper
Excessive oxidative stress in cumulus granulosa cells induced cell senescence contributes to endometriosis-associated infertility

https://doi.org/10.1016/j.redox.2020.101431Get rights and content
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Highlights

  • Endometriosis patients ovary cumulus granulosa cells (GCs) show senescence phenotype.

  • Excessive oxidative stress in GCs drives cellular senescence via activating ER stress.

  • Melatonin alleviates ER stress and GCs senescence in vitro and in vivo.

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.

Keywords

Senescence
Endometriosis
Cumulus granulosa cell
Oxidative stress
Endoplasmic reticulum stress
Infertility

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These authors contributed equally to this work.