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

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48 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbergaq004
Pages (from-to)361-372
Number of pages12
JournalMolecular Human Reproduction
Volume16
Issue number5
DOIs
Publication statusPublished - Jan 18 2010

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Keywords

  • Dioxin
  • Mitochondrial dysfunction
  • Oxidative damage
  • Trophoblast-like cell

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Genetics
  • Molecular Biology
  • Embryology
  • Obstetrics and Gynaecology
  • Reproductive Medicine

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