The effects of paternal exposure to cyclophosphamide on the development of cleavage stage embryos
Bibliographic record
Abstract
Abnormal embryonic development can arise from maternal or paternal exposure to therapeutic agents, environmental toxicants or social habits. Such exposures prior to conception may damage the gametes and have detrimental effects on the developing embryo. When male rats are exposed to the chemotherapeutic agent, cyclophosphamide, the genomic integrity of the male germ cells is altered. The goals of these studies were to determine the impact of paternal preconceptional exposure to cyclophosphamide on embryonic development and to elucidate how cleavage stage embryos respond to DNA damage in the male genome. Paternal exposure to cyclophosphamide induces sperm DNA damage and leads to the alteration of chromatin compaction during spermiogenesis. Exposure to cyclophosphamide alters the rate of sperm decondensation, as manifested by the difference in the number of zygotes within each sperm decondensation stage compared to controls. DNA double strand breaks, detected by gamma H2AX small and large foci, are enhanced during sperm decondensation, indicative of chromatin remodelling and DNA damage recognition, respectively. The damaged male genome leads to the formation of micronuclei during the first zygotic division and to a gradual developmental delay in cleavage stage embryos. The capacity of cleavage stage embryos to mount an efficient DNA damage response against the damaged male genome prevents the propagation of DNA damage to all blastomeres in subsequent cellular divisions. The activation of DNA damage responses was inappropriate, as indicated by a decrease in PARylation, in the presence of an accumulation of DNA damage in the form of large gamma H2AX foci in eight-cell embryos sired by cyclophosphamide exposed males. Thus, DNA damage induced by paternal cyclophosphamide exposure is transmitted to the early embryo, altering the progression of developmental events and activating DNA damage responses that are likely to determine embryonic fate. Furthermore, the assessment of the quality of cleavage stage embryos and developmental competence with biomarkers of the DNA damage response, such as gamma H2AX foci and PAR polymers, may be useful in developmental medicine and infertility clinics.
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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".