Haploinsufficiency of eNOS mitigates beneficial effects of maternal exercise on fetal heart development during pregestational diabetes
Bibliographic record
Abstract
Abstract Background Pregestational diabetes (PGD) increases congenital heart defect (CHD) risk over five-fold. Maternal exercise enhances endothelial nitric oxide synthase (eNOS) activity, benefiting embryos, though its causal role remains unclear. This study investigated eNOS’s role in maternal exercise-mediated protection of fetal heart development in a PGD mouse model. Methods PGD was induced in eNOS +/- or wild-type (WT) female mice via streptozotocin before breeding with WT or eNOS +/- males. Pregnant females had access to a running wheel for voluntary exercise or remained sedentary. Fetuses were collected at embryonic day (E) 18.5 for genotyping and CHD assessment. E12.5 hearts were analyzed for proliferation, apoptosis, oxidative stress, and eNOS protein levels. Results Maternal exercise normalized litter size and mortality rates in offspring of diabetic eNOS +/- females but did not reduce CHD incidence in offspring of WT or eNOS +/- females with PGD. CHDs included septal defects, double outlet right ventricle, and valve defects. Exercise increased coronary artery density but not capillary density. Proliferation deficits at E12.5 were restored by exercise, yet oxidative stress remained elevated. Maternal exercise in eNOS +/- dams during PGD did not significantly change eNOS protein levels in both eNOS +/+ and eNOS +/- fetal hearts. Offspring genotype did not impact CHD incidence, cell proliferation, apoptosis or oxidative stress. Conclusions Maternal exercise does not prevent CHDs in PGD offspring of eNOS +/- mice. Its ability to mitigate PGD-induced oxidative stress is eNOS-dependent and essential for improving heart morphology. Graphic Abstract
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| 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".