Maternal Chronic Intermittent Hypoxia During Gestation Programs Hypercholesterolemia in the Offspring
Bibliographic record
Abstract
Chronic intermittent hypoxia (CIH) is the underlying pathophysiological condition seen in individuals with obstructive sleep apnea. We have recently demonstrated that offspring exposed to maternal CIH during pregnancy exhibit reduced Liver X Receptor (LXR) protein leading to augmented expression of hepatic enzymes promoting gluconeogenesis. As LXR also plays an important role in cholesterol homeostasis, this study was done to determine the impact of diminished LXR expression on cholesterol handling by the liver in the offspring of CIH exposed pregnant mothers. Pregnant female Sprague‐Dawley rats were exposed daily to CIH (6.5% nadir; 18 cycles/h; 8h/day) from gestational day‐1 to day‐20. Control mothers were exposed to room air during pregnancy. Offspring were sacrificed at postnatal 6 and 12 weeks of age to assess early life and long‐term alterations in liver function. At both ages, male CIH offspring had significantly (p<0.05) higher total circulating cholesterol levels concomitant with significantly (p<0.05) greater body fat deposition compared to offspring exposed to gestational normoxia. Western blot analysis revealed that adult male CIH offspring at both ages had significantly (p<0.05) lower protein expression of the cholesterol catabolizing enzyme cholesterol 7α‐hydroxylase (CYP7A1), the cholesterol efflux transporter ATP‐binding cassette transporter G8 (ABCG8), and the low density lipoprotein receptor (LDLR) compared to the offspring exposed to gestational normoxia. Taken together, these data indicate that gestational CIH‐induced hypercholesterolemia in the offspring results from diminished expression of LXR target genes associated with cholesterol breakdown, excretion, and removal from the circulation. Support or Funding Information Supported in part by HSFO and CIHR
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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".