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Dioxin-like rather than non-dioxin-like PCBs promote the development of endometriosis through stimulation of endocrine–inflammation interactions

Abstract

Polychlorinated biphenyls (PCBs) contain 209 congeners with various structure–activities. Exposure to PCBs was related to disorders of female reproduction. Endometriosis (EM) is an estrogen- and inflammation-dependent disease with high prevalence and severe health outcomes. Epidemiological studies have shown the effects of PCBs exposure on EM in regard to various structures of PCBs. However, little evidence is available from the toxicology considering the structure of PCBs. In the study, environmentally relevant concentrations of PCBs were used to treat primary cultured endometrial cells and an EM mouse model. Dioxin-like CB126, but not non-dioxin-like CB153, significantly enhanced 17β-estradiol (E2) biosynthesis in a dose-dependent manner. Among the genes related to estrogen metabolism, the level of 17β-hydroxysteroid dehydrogenase 7 (HSD17B7) showed significant increase following CB126 exposure. We further found that CB126 exposure decreased the methylation of the HSD17B7 promoter. Elevated expression of HSD17B7 was observed in the eutopic endometrium of EM patients. CB126 rather than CB153 triggered the inflammatory response by directly stimulating the secretion of inflammatory factors and indirectly reducing the level of lipoxin A4 (LXA4). Furthermore, the inflammation enhanced the expression of HSD17B7. Antagonism of the aryl hydrocarbon receptor (AhR) diminished the effects induced by CB126. In vivo, the PCB-treated EM mouse model confirmed that CB126 rather than CB153 increased the levels of both E2 and inflammatory factors in peritoneal fluid and promoted the development of endometriotic lesions. In all, CB126, but not CB153, triggered EM development by stimulating estrogen biosynthesis, inflammation and their interactions and that these effects were mediated by the AhR receptor.

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Acknowledgments

We gratefully acknowledged the supports by National Natural Science Foundation of China (41390240, 21477123, 21107107) and Institute of Urban Environment, Chinese Academy of Sciences (IUEMS201405).

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Correspondence to Qiansheng Huang or Sijun Dong.

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The authors declare that they have no actual or potential competing financial interests.

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Qiansheng Huang and Yajie Chen have contributed equally to the paper.

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Huang, Q., Chen, Y., Chen, Q. et al. Dioxin-like rather than non-dioxin-like PCBs promote the development of endometriosis through stimulation of endocrine–inflammation interactions. Arch Toxicol 91, 1915–1924 (2017). https://doi.org/10.1007/s00204-016-1854-0

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  • DOI: https://doi.org/10.1007/s00204-016-1854-0

Keywords

  • Polychlorinated biphenyls
  • Endometriosis
  • HSD17B7
  • LXA4
  • Methylation