Investigating the effects of chemotherapeutic agents for testicular cancer on the male reproductive system, progeny outcome and spermatogonial stem cells in the rat
Bibliographic record
Abstract
Testicular cancer (TC) is the most common type of cancer affecting men between the ages of 15 and 35 years old. The standard chemotherapy for testicular cancer is a combination of bleomycin, etoposide and cisplatin (called BEP regimen) that results in cure rates over 90%. In order to determine whether the BEP regimen induces adverse effects on the male reproductive system and progeny outcomes, in chapter 2, male Sprague-Dawley rats were treated with a combination of bleomycin, etoposide and cisplatin for 9 consecutive weeks. BEP treatment resulted in decreased testis and epididymal weights, and sperm counts, but despite the dramatic effects on spermatogenesis, paternal exposure to BEP did not affect fertility, nor were there adverse effects on litter size, pre-and post-implantation losses, fetal weight and death rate or sex ratio observed among progeny sired by treated males; however, increased mortality was observed in pups during the perinatal phase. In chapter 3, we evaluated the reversibility of a subchronic BEP treatment on the male reproductive system and progeny outcome. Male rats were treated with a 9 week subchronic BEP regimen; progeny outcome parameters were determined every 3 weeks for a total of 9 weeks during recovery. Subchronic BEP caused transient defects on spermatogenesis; however, a prolonged increase in pre-implantation loss was observed up to 9 weeks after completion of the treatment, suggesting that spermatogonial stem cells may be affected. Thus, in chapter 4, the impact of BEP chemotherapy on spermatogonial stem cells (SSCs) was investigated. Testicular cell suspension from BEP-treated GCS-EGFP transgenic rats were transplanted into busulfan-treated recipient nude mice. The number and length of colonies-derived from transplanted stem cells was assessed as a function of stem cell activity after exposure to BEP. Finally, in chapter 5, we assessed the in vitro effects of bleomycin, etoposide and cisplatin alone and in combination on cultured rat stem/progenitor spermatogonia. These results indicated that BEP has deleterious effects on male reproductive functions including SSCs and progeny outcomes.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".