Consequences of paternal exposure to the anti-cancer drug, cyclophosphamide, on rat pre-implantation development
Bibliographic record
Abstract
Administration of cyclophosphamide to males targets the germ cells and causes DNA damage including single strand breaks and DNA-DNA cross links. When males are treated with a chronic low dose of cyclophosphamide and then mated to normal females, progeny loss is manifested at the pre- and post-implantation stages of development. The earliest events that lead to embryonic loss were traced to day 2 of gestation when embryos had a decreased DNA synthesis profile and lower cell numbers than control litters. I investigated the hypothesis that chronic exposure of male rats to cyclophosphamide alters zygotic gene expression thus leading to embryonic loss. To assess DNA damage in the embryo, the Comet Assay was performed on 1-cell stage embryos. A significant number of embryos sired by cyclophosphamide-treated males showed the appearance of the Comet indicative of the effect of damaged sperm on the embryos starting from the 1-cell stage. Using a candidate gene approach, the antisense RNA (aRNA), I described the presence of several DNA repair gene families in normal embryos. Progeny sired by cyclophosphamide-treated males manifested a differential expression profile for several of these genes when compared to controls, suggestive of the ability of the embryo to respond to damaged sperm through the major DNA repair systems. To study the functional capacity of progeny sired by cyclophosphamide-treated males, I assessed total RNA synthesis in both groups; while control litters showed a peak of RNA synthesis at the 4-cell stage, the treatment group showed constant low expression throughout the stages examined. I mapped the profile of a number of gene families whose roles are essential for early development in both control and cyclophosphamide-treated groups. While control embryos showed a peak of expression for the majority of genes at the 8-cell stage, that of the cyclophosphamide-group showed an early induction at the 2-cell stage, indicative of loss of the tightly regulated
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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) | 0.002 | 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".