Epigenetic programming in the preimplantation rat embryo is disrupted by chronic paternal cyclophosphamide exposure
Bibliographic record
Abstract
Preconceptional paternal exposure to cyclophosphamide, a widely used anticancer agent, leads to increases in embryo loss, malformations, and behavioral deficits in offspring; these abnormalities are transmissible to subsequent generations [Auroux, M., Dulioust, E., Selva, J. & Rince, P. (1990) Mutat. Res. 229, 189-200]. Little information exists on the mechanisms underlying this male-mediated developmental toxicity. We assessed the impact of paternal cyclophosphamide exposure on the dynamic regulation of histone H4 acetylation at lysine 5 and DNA methylation in preimplantation rat embryos. Zygotes sired by drug-treated males displayed advanced developmental progression, increased pronuclear areas, and disruption of the epigenetic programming of both parental genomes. Early postfertilization zygotic pronuclei were hyperacetylated; by mid-zygotic development, male pronuclei were dramatically hypomethylated, whereas female pronuclei were hypermethylated. Micronuclei were substantially elevated, and histone H4 acetylation at lysine 5 localization to the nuclear periphery was disrupted in two-cell embryos fertilized by cyclophosphamide-exposed spermatozoa. This finding demonstrates that paternal exposure to this drug induces aberrant epigenetic programming in early embryos. We hypothesize that disturbances in epigenetic programming contribute to heritable instabilities later in development, emphasizing the importance of epigenetic risk assessment after chemotherapy.
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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 | 0.001 | 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) | 0.000 | 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".