Fetal Exposure to Low Levels of the Plasticizer DEHP Predisposes the Adult Male Adrenal Gland for Endocrine Disruption
Bibliographic record
Abstract
In utero exposure to endocrine disrupting chemicals (EDCs) may affect adult health. Di-(2-ethylhexyl) phthalate (DEHP) is an EDC widely used in the production of polyvinyl chloride products and an ubiquitous environmental contaminant. We used a rat model system to show that fetal exposure to DEHP decreased levels of major steroid hormones in adulthood and that environmentally-relevant levels of DEHP affected both gene expression and epigenomic loci that were affected by exposure to high levels. In the adrenal gland, we reported that the peroxisome proliferator-activated receptor (PPAR) and cholesterol biosynthesis pathways were sensitive targets of DEHP. We hypothesized that low levels of DEHP exposure insult the endocrine system (a "first hit") and increase its susceptibility to later exposure ("second hit") and subsequent disease. Here, we demonstrate that a second hit in the adult offspring exposed in utero to low levels of DEHP affected serum aldosterone levels. To unveil the first hit influence of early DEHP exposure, we treated in utero DEHP-exposed adult offspring with stressors that targeted the PPAR or cholesterol biosynthesis pathways. Treatment with the PPAR-gamma antagonist T0070907 reduced serum aldosterone compared to animals not exposed to DEHP in utero. Analysis of gene expression in animals that were subjected to both early and late exposure revealed deregulation of genes for the potassium channel Kcnk5 and the retinoid-X receptors (RXR) Rxra and Rxrb, indicating that these entities are linked to endocrine disruption. We propose that early exposure to environmental doses of DEHP predisposes the animal for disease later in life.
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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 | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".