Avian-Specific Evidence for an Estrogen Receptor Agonism Adverse Outcome Pathway Based on Chicken Embryos and LMH 3D Spheroids Exposed to Ethinylestradiol and Bisphenol A
Bibliographic record
Abstract
Several adverse outcome pathways (AOPs) describe the effects of endocrine disrupting compounds on estrogen signaling. Substantial data support an AOP related to estrogen receptor (ER) antagonism, leading to decreased fecundity in fish. In this study, data were generated for an ER agonism AOP leading to reduced fecundity in avian species (AOP537). Chicken embryos and the chicken leghorn male hepatoma cell line, LMH, were used to elucidate key events associated with estrogen signaling following exposure to 17α-ethinylestradiol (EE2) and bisphenol A (BPA). Embryos were exposed via egg injection. Viability and hepatic estrogen-responsive gene expression data were collected at midincubation (embryonic day [ED] 11). Changes in plasma vitellogenin (VTG), gonad morphology and growth were evaluated prior to pipping (ED20). Both chemicals dysregulated estrogen-responsive genes in hepatic tissue and increased plasma VTG concentrations. In LMH spheroids, EE2 and BPA altered estrogen-responsive genes and VTG concentrations at 24 and 48 h, respectively. Gonadal histology revealed oocyte-type cells and loss of testicular cords in male embryos exposed to EE2 and BPA. Overall, EE2 and BPA upregulated VTG mRNA expression, increased plasma VTG, and caused impairments in gonadal development. These results contribute avian-specific evidence to support an endocrine disruption AOP describing the relationship between disrupted VTG synthesis and impaired reproduction.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 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) | 0.001 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".