2. Academic Validation
  3. Toxicity mechanism of acrolein on energy metabolism disorder and apoptosis in human ovarian granulosa cells

Toxicity mechanism of acrolein on energy metabolism disorder and apoptosis in human ovarian granulosa cells

  • Toxicology. 2024 Jun 10:153861. doi: 10.1016/j.tox.2024.153861.
Xueping Liu 1,  Rongxia Li 2,  Zi Xiu 3,  Siling Tang 1,  Yancang Duan 4
Affiliations

Affiliations

  • 1 College of Basic Medical, Hebei University of Chinese Medicine, Shijiazhuang 050091, Hebei Province, China.
  • 2 College of Basic Medical, Hebei University of Chinese Medicine, Shijiazhuang 050091, Hebei Province, China; Department of Gynecology Medicine, The Second Hospital of Hebei Medicine University, Shijiazhuang 050004, Hebei Province, China.
  • 3 College of Acupuncture-Moxibustion and Tuina, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei Province, China.
  • 4 College of Integrated Traditional Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050091, Hebei Province, China; Hebei Collaborative Innovation Center of Integrated Chinese and Western Medicine on Reproductive Disease, Shijiazhuang 050091, Hebei Province, China; Hebei Key Laboratory of Integrative Medicine on Liver-kidney Patterns, Shijiazhuang 050091, Hebei Province, China. Electronic address: China.duanyancang@hebcm.edu.cn.
PMID: 38866128 DOI: 10.1016/j.tox.2024.153861
Abstract

Acrolein (ACR), an unsaturated, highly reactive aldehyde, is a widespread environmental toxin. ACR exerts permanent and irreversible side effects on ovarian functions. Granulosa cells play a crucial role in supporting ovarian function. Thus, in this study, we investigated the toxicity effects of granulosa cells induced by ACR. Following treatment with varying ACR concentrations (0, 12.5, 25, 50, and 100μM), we observed that ACR exposure induced Reactive Oxygen Species accumulation, mitochondrial energy metabolism disorder, and Apoptosis in KGN cells (a human ovarian granulosa cell line) in a dose-dependent manner. In addition, mitochondrial biogenesis in KGN cells displayed biphasic changes after ACR exposure, with activation at a low ACR dose (12.5μM), but inhibition at higher ACR doses (≥50μM). SIRT1/PGC-1α-mediated mitochondrial biogenesis is crucial for maintaining intracellular mitochondrial homeostasis and cellular function. The inhibition/activation of the SIRT1/PGC-1α pathway in KGN cells validated its role in ACR-induced damage. The results indicated that the inhibition of the SIRT1/PGC-1α pathway aggravated ACR-induced cell damage, whereas its activation partially counteracted ACR-induced cell damage. This study attempted to uncover a novel mechanism of ACR-induced ovarian toxicity so as to provide an effective treatment option for safeguarding female reproductive health from the adverse effects of ACR.

Keywords

Acrolein; SIRT1/PGC-1α; apoptosis; energy metabolism disorder; granulosa cells.

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