Stress response mechanisms during rat spermatogenesis and the effects of the anticancer agent cyclophosphamide
Bibliographic record
Abstract
Exposure of males to drugs or environmental chemicals can alter reproductive health and affect progeny outcome. The quality of the male germ cell is determined in part by the presence and function of stress response mechanisms. During spermatogenesis, different germ cell types display differential susceptibility to toxicants, suggesting there is variation in the presence and function of stress response mechanisms. Exposure of male rats to cyclophosphamide, a commonly used anticancer and immunosuppressive drug, alters male fertility and progeny outcome in a male-germ cell phase specific manner. The hypothesis of this thesis is that stress response mechanisms are differentially expressed during rat spermatogenesis and that their expression is involved in the response to the alkylating agent cyclophosphamide. The first objective of this thesis was to elucidate the expression of stress response genes at different stages of male germ cell development. Using cDNA arrays, the expression of several gene families was profiled in rat pachytene spermatocytes, round spermatids and elongating spermatids. Stress response genes were found to be differentially expressed during spermatogenesis. The second objective was to determine whether the expression of stress response genes was modified by exposure to cyclophosphamide. Acute and chronic cyclophosphamide treatment altered gene expression in a cell- and treatment-specific manner. Due to the known deleterious effects of cyclophosphamide on meiotic events, the last goal was to assess the ability of pachytene spermatocytes to undergo the meiotic G21/M transition. The delayed meiotic progression induced by acute cyclophosphamide treatment, likely to be a checkpoint response, contrasted with the lack of delay after chronic drug exposure. Together these results show that male germ cells are differentially equipped with mechanisms of stress response. Furthermore, cyclophosphamide alters the expression of stres
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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".