Open AccessReactive oxygen species‐induced SIAH1 promotes granulosa cells' senescence in premature ovarian failure
Author(s) -
Lin Li,
Gao Wujiang,
Chen Yumei,
Li Taoqiong,
Sha Chunli,
Chen Lu,
Yang Meiling,
Wei Hong,
Chen Yunpeng,
Zhu Xiaolan
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17264
Subject(s) - senescence , telomere , reactive oxygen species , dna damage , biology , premature ovarian failure , granulosa cell , andrology , medicine , microbiology and biotechnology , cancer research , endocrinology , ovary , dna , biochemistry
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.