Estrogen-independent actions of environmentally relevant AhR-agonists in human endometrial epithelial cells

Cornelia Willing, Willing C, Peich M, Marco Peich, Adrian Danescu, Danescu A, Kehlen A, Astrid Kehlen, Paul A Fowler, Paul Fowler, Sabine Hombach-Klonisch, Sabine Hombach‐Klonisch
Molecular human reproduction · 2010 · vol. 17(2) , pp. 115–126 · doi:10.1093/molehr/gaq081 · PMID:20876610 · W2131015297
Lab / animal OA: bronze CC0 ⤵ 8 in-corpus citations
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Environmentally relevant aryl hydrocarbon receptor (AhR)-activating pollutants alter human endometrial epithelial cell migration and stress responses independently of estrogenic actions.

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Abstract

The human endometrium is a cyclically regenerating organ under the influence of ovarian steroid hormones. Disturbances in this highly coordinated regulation of endometrial proliferation and differentiation may result in infertility and diseases such as endometriosis and endometrial cancer. Environmental toxins belonging to the group of polyhalogenated aromatic hydrocarbons (PAHs) are lipophilic xenobiotics, which accumulate in biological systems. PAHs have been implicated in the etiology of uterine pathologies, including infertility, endometriosis and endometrial cancer. However, suitable cellular models of the endometrium are lacking and the molecular mechanism of PAH action in the endometrium is not fully understood. In this study, we have characterized a previously established immortalized human telomerase reverse transcriptase (hTERT) endometrial epithelial cell (hTERT-EEC) model as a responsive in vitro cell model to investigate the cellular and molecular mechanisms of selected environmentally relevant PAH in human EECs. We show that dioxin-type PAHs activate the endogenous arylhydrocarbon receptor (AhR) signaling pathway in hTERT-EEC in a time-, concentration- and congener-specific manner and that the induction of AhR target genes is modulated by estrogen. Strikingly, AhR activation did not interfere with estrogenic actions in these EECs. Independent of their ability to bind to AhR, the PAHs investigated here increased cell migration by hTERT-EEC. Furthermore, we have identified several candidates by proteomic analysis, which are involved in heat shock responses and protein modification and turnover. Our data suggest that AhR-activating environmental pollutants directly alter endometrial cell stress responses and metabolism independent of estrogenic actions.

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Condition tags

endometriosisinfertility

MeSH descriptors

Dioxins Endometrium Environmental Pollutants Epithelial Cells Hydrocarbons, Halogenated Receptors, Aryl Hydrocarbon Blotting, Western Blotting, Western Cell Movement Cell Movement Cell Movement Cell Proliferation Cell Proliferation Cell Proliferation Cells, Cultured Cells, Cultured Cells, Cultured Dioxins Dioxins Dioxins

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Cited by (7)

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