2. Academic Validation
  3. Reactive oxygen species-induced SIAH1 promotes granulosa cells' senescence in premature ovarian failure

Reactive oxygen species-induced SIAH1 promotes granulosa cells' senescence in premature ovarian failure

  • J Cell Mol Med. 2022 Apr;26(8):2417-2427. doi: 10.1111/jcmm.17264.
Li Lin 1 2,  Wujiang Gao 1 2,  Yumei Chen 2,  Taoqiong Li 1 2,  Chunli Sha 1 2,  Lu Chen 1 2,  Meiling Yang 2,  Hong Wei 2,  Yunpeng Chen 3,  Xiaolan Zhu 1 2 4
Affiliations

Affiliations

  • 1 Reproductive Center, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China.
  • 2 Department of Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China.
  • 3 Department of Radiology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.
  • 4 International Genome Center of Jiangsu University, Zhenjiang, China.
PMID: 35261172 DOI: 10.1111/jcmm.17264
Abstract

Reactive Oxygen Species (ROS) exposure triggers granulosa cells' (GCs) senescence, which is an important causal factor for premature ovarian failure (POF). However, underlying mechanism in this process remains unknown. In our study, we observed increased ROS levels in POF ovarian tissues, POF patient follicular GCs and cyclophosphamide (CTX) pretreated GCs. Correspondingly, increased SIAH1, reduced TRF2 and GC senescence were also found in these cases. Silencing of SIAH1 rescued ROS-induced TRF2 reduction and cell senescence in GCs. Moreover, SIAH1 co-localized with TRF2 in the cytoplasm, facilitating its ubiquitination degradation, further leading to telomere abnormalities in GCs. In conclusion, our findings indicate that ROS induces telomere abnormalities by augmenting SIAH1-mediated TRF2 degradation, leading to cell senescence in GCs in POF processing.

Keywords

SIAH1; premature ovarian failure; reactive oxygen species; senescence; telomere.

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