Cigarette Smoke Exposure Triggers Autophagy-Mediated Ovarian Follicle Loss in a Mouse Model.
Bibliographic record
Abstract
Delayed conception, decreased success in assisted reproductive technologies and premature ovarian failure have all been reported in female smokers compared with non-smokers. Recently we reported that exposure to cigarette smoke resulted in significant primordial follicle loss that was not associated with activation of either the intrinsic or extrinsic apoptosis pathways as shown by absence of an effect on TUNEL staining, DNA laddering, Bax expression and activated caspase-3 expression compared to controls. However, a significant decrease in the expression of the inhibitor of apoptosis B-cell lymphoma-2 (Bcl-2) in ovaries of exposed mice vs. controls was found. Intriguingly, while Bcl-2 is a key regulatory protein in the apoptosis pathway inhibiting cell death by blocking the action of Bax, it has also been implicated in inhibiting cell death by preventing Beclin-1 from performing its role in another cell death pathway, autophagy (self-digestion). Although cigarette smoking in humans and cigarette smoke (CS) exposure in mice depletes the primordial follicle population, the mechanism of action is unknown. Therefore, the effect of cigarette smoke exposure, at concentrations representative of human exposure, on selective stage-dependent destruction of follicles in mouse ovaries was studied. In the present study, mice were exposed to CS or room air (control) for 8 weeks. Ovaries were excised and processed for electron microscopy (EM), Western blotting, immunohistochemistry (IHC) and quantitative real time-PCR (q-PCR). Markers of survival were decreased, as was the ovary's ability to cope with the production of reactive oxygen species. Increased expression of loxI and lc3, markers if autophagy, and an increase in the presence of autophagosomes in the granulosa cells of smoke exposed ovaries compared to controls were documented. The results of the present study suggest that exposure to cigarette smoke causes significant primordial follicle loss following the production of reactive oxygen species and the triggering of the autophagy pathway through a decrease in Bcl-2 expression. (platform)
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".