Endocrine disruptor, dioxin (TCDD)-induced mitochondrial dysfunction and apoptosis in human trophoblast-like JAR cells

Su Chee Chen, Tien Ling Liao, Yau Huei Wei, Chii Reuy Tzeng, Shu Huei Kao

研究成果: 雜誌貢獻文章同行評審

55 引文 斯高帕斯(Scopus)

摘要

The endocrine disruptor 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been demonstrated to disrupt hormone signalling, reduce fertility, interfere with embryo development and cause spontaneous miscarriage in humans. The precise mechanisms of its effects on early implantation in humans are still unclear. In this study, we examined the relationship between mitochondrial function and dioxin-induced toxicity in JAR cells, a human trophoblast-like cell line. Several experiments were performed to address the effects of TCDD on cell viability, reactive oxygen species (ROS) generation, oxidative damage (indicated by the presence of lipoperoxides and oxidized DNA bases), mitochondrial DNA (mtDNA) copy number, ATP content, mtDNA mutations and the protein levels of p53, Bax, Bcl2, cytochrome c and caspase 3. Increased oxidative damage and mitochondrial dysfunction in TCDD-treated trophoblast-like cells was demonstrated. A 2.58-fold increase in lipid peroxides was detected in cells treated with 2 nM TCDD for 4 h. The oxidative DNA damage marker 8-hydroxy-2′-deoxyguanosine was significantly increased by TCDD treatment in a time-dependent manner. Meanwhile, reductions in mtDNA copy number and ATP content and an increase in mtDNA deletions were found. Furthermore, we observed increased apoptosis, p53 accumulation, Bax overexpression, cytochrome c release and sequential caspase 3 activation after TCDD exposure. These results indicate that oxidative damage and mitochondrial dysfunction may be responsible for the apoptotic effects of TCDD.
原文英語
文章編號gaq004
頁(從 - 到)361-372
頁數12
期刊Molecular Human Reproduction
16
發行號5
DOIs
出版狀態已發佈 - 一月 18 2010

ASJC Scopus subject areas

  • 細胞生物學
  • 發展生物學
  • 遺傳學
  • 分子生物學
  • 胚胎學
  • 婦產科
  • 生殖醫學

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