Estrogen-independent actions of environmentally relevant AhR-agonists in human endometrial epithelial cells
Why this work is in the frame
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Bibliographic record
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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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it