Acute cyclophosphamide exposure has germ cell specific effects on the expression of stress response genes during rat spermatogenesis
Bibliographic record
Abstract
Exposure of male rats to cyclophosphamide, a commonly used anticancer and immunosuppressive drug, has been shown to alter fertility and progeny outcome in a male germ cell phase-specific manner. The effect of toxicant exposure on male germ cells depends in part on the stress response mechanisms present during the different stages of spermatogenesis. To assess how acute cyclophosphamide exposure affects the expression of stress response genes, we examined the expression of 216 genes, using gene expression arrays, in isolated rat spermatogenic cell types (pachytene spermatocytes, round spermatids, and elongating spermatids). Cyclophosphamide exposure affected gene expression in all cell types but most dramatically in round spermatids. Increased transcript levels were observed for 30 genes in round spermatids compared to seven genes in pachytene spermatocytes and two in elongating spermatids. The expression of genes involved in apoptosis, DNA-damage recognition and repair, transcriptional activation, and in the heat shock protein-chaperone response was most affected by cyclophosphamide in round spermatids. Our results demonstrate that cyclophosphamide alters the expression of stress response genes during spermatogenesis in a germ cell-specific manner. The greater response of round spermatids to cyclophosphamide suggests that this cell type may be more susceptible to the damaging effects induced by this drug, possibly due to the chromatin remodeling that is taking place at this stage of spermatogenesis. This observation is consistent with the reported higher level of abnormal progeny outcome seen when the germ cells were first exposed to cyclophosphamide as round spermatids.
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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) | 0.001 | 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".