Effect of valproic acid on glutathione homeostasis in mouse whole embryo cultures
Bibliographic record
Abstract
Valproic acid (2-propylpentanoic acid, VPA) is a clinically used anti-epileptic drug that has been shown to induce embryonic defects in both humans and mice. We have applied a whole mouse embryo culture system to investigate valproic acid-induced teratogenecity and its effects on glutathione homeostasis and on Hoxa2 gene expression. Our results have demonstrated a correlation between VPA dose and total morphological score. The incidence of dysmorphogenesis increased significantly (35%, 47% and 88%) with increasing doses of VPA (100, 200 and 400 µg/ml, respectively). In addition, we have observed neural tube defects and craniofacial abnormalities including fusion of the first and second brachial arches. Glutathione homeostasis was altered as indicated by an increase in GSSG/GSH ratio in all treatment groups. Our data also show dosedependent inhibition of Hoxa2 gene expression as measured by RT-PCR in whole embryo cultures after VPA treatment. Results indicate that VPA alters glutathione homeostasis in cultured mouse embryos and may induce teratogenicity by inhibiting Hoxa2 gene expression.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".