In Utero Exposure to the Endocrine Disruptor Di-(2-Ethylhexyl) Phthalate Induces Long-Term Changes in Gene Expression in the Adult Male Adrenal Gland
Bibliographic record
Abstract
The plasticizer di-(2-ethylhexyl) phthalate (DEHP) is used to add flexibility to polyvinylchloride polymers and as a component of numerous consumer and medical products. DEHP and its metabolites have been detected in amniotic fluid and umbilical cord blood, suggesting fetal exposure. In the present study, we used an in utero exposure model in which pregnant rat dams were exposed to 1- to 300-mg DEHP/kg·d from gestational day 14 until birth. We previously reported that this window of exposure to environmentally relevant doses of DEHP resulted in reduced levels of serum testosterone and aldosterone in adult male offspring and that the effects on aldosterone were sustained in elderly rats and resulted in decreased blood pressure. Here, we characterized the long-term effects of in utero DEHP exposure by performing global gene expression analysis of prepubertal (postnatal d 21) and adult (postnatal d 60) adrenal glands. We found that the peroxisome proliferator-activated receptor and lipid metabolism pathways were affected by DEHP exposure. Expression of 2 other DEHP targets, hormone-sensitive lipase and phosphoenolpyruvate carboxykinase 1 (Pck1), correlated with reduced aldosterone levels and may account for the inhibitory effect of DEHP on adrenal steroid formation. The angiotensin II and potassium pathways were up-regulated in response to DEHP. In addition, the potassium intermediate/small conductance calcium-activated channel Kcnn2 and 2-pore-domain potassium channel Knck5 were identified as DEHP targets. Based on this gene expression analysis, we measured fatty acid-binding protein 4 and phosphoenolpyruvate carboxykinase 1 in sera from control and DEHP-exposed rats and identified both proteins as putative serum biomarkers of in utero DEHP exposure. These results shed light on molecular targets that mediate DEHP long-term effects and, in doing so, provide means by which to assess past DEHP exposure.
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How this classification was reachedexpand
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 | 0.000 | 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 | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".