2. Academic Validation
  3. TRIM28-Mediated Excessive Oxidative Stress Induces Cellular Senescence in Granulosa Cells and Contributes to Premature Ovarian Insufficiency In Vitro and In Vivo

TRIM28-Mediated Excessive Oxidative Stress Induces Cellular Senescence in Granulosa Cells and Contributes to Premature Ovarian Insufficiency In Vitro and In Vivo

  • Antioxidants (Basel). 2024 Mar 1;13(3):308. doi: 10.3390/antiox13030308.
Chong Zhou 1 2,  Dandan Li 2 3,  Jinxia He 4,  Tao Luo 1 2 5,  Yiting Liu 1 2,  Yue Xue 1 2,  Jian Huang 2,  Liping Zheng 2 3 6 7,  Jia Li 1 2
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang 330031, China.
  • 2 Key Laboratory of Reproductive Physiology and Pathology of Jiangxi Province, Jiangxi Medical College, Nanchang University, Nanchang 330031, China.
  • 3 HuanKui College, Nanchang University, Nanchang 330031, China.
  • 4 Reproductive Medical Center, Jiangxi Maternal and Child Health Hospital, Affiliated Maternal and Child Health Hospital of Nanchang University, Nanchang 330006, China.
  • 5 Institute of Life Science, Nanchang University, Nanchang 330031, China.
  • 6 School of Public Health, Jiangxi Medical College, Nanchang University, Nanchang 330006, China.
  • 7 Jiangxi Provincial Key Laboratory of Preventive Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330006, China.
PMID: 38539841 DOI: 10.3390/antiox13030308
Abstract

Premature ovarian insufficiency (POI) is a clinical syndrome of ovarian dysfunction characterized by the abnormal alteration of hormone levels such as FSH and E2. POI causes infertility, severe daily life disturbances, and long-term health risks. However, the underlying mechanism remains largely unknown. In this study, we found that POI is associated with the cellular senescence of ovarian granulosa cells, and TRIM28 mediates oxidative stress (OS)-induced cellular senescence in granulosa cells. Mechanistically, OS causes a decrease in TRIM28 protein levels in KGN cells. Subsequently, it triggers an increase in the levels of Autophagy marker proteins ATG5 and LC3B-II, and the downregulation of p62. Abnormal Autophagy induces an increase in the levels of cellular senescence markers γ-H2A.X, P16, and P21, provoking cellular senescence in vitro. The overexpression of ovarian TRIM28 through a microinjection of lentivirus attenuated Autophagy, cellular senescence, and follicular atresia in the ovaries of POI mice and improved mouse fertility in vivo. Our study highlights the triggers for POI, where the reduction of TRIM28, which is regulated by Reactive Oxygen Species, causes follicular atresia and POI via triggering Autophagy and inducing granulosa cell senescence. Shedding light on TRIM28 may represent a potential intervention strategy for POI.

Keywords

TRIM28; autophagy; cellular senescence; granulosa cells; oxidative stress; premature ovarian insufficiency.

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