CCL5 secreted by senescent theca‐interstitial cells inhibits preantral follicular development via granulosa cellular apoptosis. Issue 12 (20th May 2019)

• Record Type: Journal Article
• Authors: Shen, Lu; Chen, Yuan; Cheng, Jing; Yuan, Suzhen; Zhou, Su; Yan, Wei; Liu, Junfeng; Luo, Aiyue; Wang, Shixuan
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 12(2019:Dec.)
• Page Start: 22554
• Page End: 22564
• Publication Date: 2019-05-20
• Subjects: CCL5 -- follicle development -- ovarian aging -- SASP -- theca‐interstitial cell; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.28819
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: As a fundamental aging mechanism, cellular senescence causes chronic inflammation via the senescence‐associated secretory phenotype (SASP). Theca‐interstitial cells are an essential but little‐studied component of follicle development in the ovarian microenvironment. In the present study, we observed significant cellular senescence in theca‐interstitial cells and secretion of chemokine (C‐C motif) ligand 5 (CCL5) by these cells during aging. Furthermore, we aimed to investigate whether and how senescence‐associated secretory phenotype (SASP)‐associated CCL5 may be involved in follicle development. Increased levels of CCL5 in the microenvironment of follicles attenuated preantral follicle growth, survival, and estradiol secretion. Oocyte maturation and the expression of zona pellucida 3 and differentiation factor 9 (GDF9) were also inhibited by CCL5. Granulosa cell apoptosis in follicles was promoted by CCL5, accompanied by the phosphorylation of nuclear factor‐κB by CCL5 and inhibition of the PI3K/AKT pathway. These results suggest that SASP‐associated CCL5 produced by senescent theca‐interstitial cells may impair follicle development and maturation during ovarian aging by promoting granulosa cell apoptosis. Abstract : We observed significant cellular senescence in theca‐interstitial cells and secretion of CCL5 by these cells during aging. The SASP‐associated CCL5 produced by senescent theca‐interstitial cells may impair follicle development and maturation during ovarian aging by promoting granulosa cell apoptosis.