Benzo[a]pyrene Inhibition of Follicular Development and Survival Is Associated with Dysregulation of Hsp90, Bax, CYP1A1, and CYP1B1 Expression.
Bibliographic record
Abstract
Decreased fertility and poorer response to ovulation induction have been reported in women who smoke compared to non-smokers. We have demonstrated the cytotoxic effects of benzo[a]pyrene (B[a]P), an important component of cigarette smoke, on antral follicle development, on follicular atresia and steroid production. However, the mechanisms underlying the deleterious effects of B[a]P on follicular development are unknown. We hypothesize that B[a]P binds with and activates the aryl hydrocarbon receptor (AhR) signaling pathway which causes oxidative stress in follicles that leads to inhibition of follicular development. Isolated mouse follicles (100–130 μm) were cultured for 13 days in the absence (controls) or presence of increasing B[a]P concentrations (1.5 – 45 ng/ml). Follicular development and viability were assessed prior to refreshment on days 4 (preantral follicles), 8 (antral follicles) and 12 (preovulatory follicles) of culture. On day 8, healthy follicles were collected, snap frozen and stored in liquid nitrogen. On day 12, preovulatory follicles were stimulated with r-hCG and EGF. Following 18 h (day 13) after stimulation, cumulus cell-oocyte complexes (COCs) were collected and snap frozen. Using real-time RT-PCR, Cdk4, Ccnd2, Cdk2, AhR, Hsp90, CYP1A1, CYP1B1 and Bax transcripts were quantified in follicles and COCs collected and stored on days 8 and 13, respectively. On day 8, Cdk4, Ccnd2, Cdk2 and AhR expression levels were comparable between controls and follicles exposed to B[a]P while the level of CYP1A1 mRNA was significantly higher in follicles exposed to B[a]P. On day 13, Bax, Hsp90 and CYP1B1 mRNA levels were significantly higher in COCs of follicles exposed to 45 ng/ml B[a]P compared to controls. Therefore, we suggest that decreased human fecundity associated with cigarette smoking may be related to activation of the AhR signalling pathway (increased CYP1A1 and CYP1B1 expression), oxidative stress (Hsp90), and apoptosis (Bax) pathways.
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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".