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Decreased expression of IDH1 by chronic unpredictable stress suppresses proliferation and accelerates senescence of granulosa cells through ROS activated MAPK signaling pathways by Junyan Sun; Ying Guo; Yihui Fan; Qian Wang; Qiuwan Zhang; Dongmei Lai is a scholarly article available to read on EtoBox.

What is Decreased expression of IDH1 by chronic unpredictable stress suppresses proliferation and accelerates senescence of granulosa cells through ROS activated MAPK signaling pathways about?

Studies suggested that psychosocial stress was associated with female fertility decline, but the underlying mechanisms remained unclear. Granulosa cells (GCs) are important somatic cells to support follicular development and oocyte maturation. Herein, by using a mouse model of chronic unpredictable stress (CUS), we found that CUS induced oxidative stress damage in mouse ovaries, also inhibited GCs proliferation and accelerated GCs senescence. Isocitrate dehydrogenase-1 (IDH1), an antioxidant related gene by generating NADPH, was shown to be downregulated in GCs of CUS mice. Consistently, IDH1 knockdown inhibited cell proliferation and accelerated cellular senescence in KGN cells in vitro. In addition, IDH1 knockdown increased ROS content, induced autophagy activation and triggered cell cycle arrest in S and G2/M phases in KGN cells, which could be rescued by Nacetyl-L-cysteine (NAC), a ROS scavenger in these cells. Besides, IDH1 knockdown activated MAPK signaling pathways, including ERK, JNK and p38 signaling pathways in KGN cells, while NAC could suppress the activation. Through using inhibitors of MAPK signaling pathways, we showed that the activation of ERK pathway participated

Author

Junyan Sun; Ying Guo; Yihui Fan; Qian Wang; Qiuwan Zhang; Dongmei Lai

Publisher

Elsevier BV

Published

2021

Language

EN