Prenatal Exposure to Disrupted Methyl Metabolism Affects Expression & Allele‐Specific Methylation of H19/Igf2 in Brain
Bibliographic record
Abstract
Epigenetic processes may play a role in the metabolic programming associated with prenatal nutrition. We studied the effect of prenatal exposure to disrupted maternal methyl metabolism on expression and allele‐specific methylation of H19/Igf2 in brain. H19/Igf2 expression is regulated by a differentially methylated domain (DMD). We studied F1 hybrid offspring from male Cast / EiJ mice and female C57BL6/J mice [with ( Cbs +/‐) and without ( Cbs +/+) heterozygous disruption of the cystathionine‐ß ‐synthase gene] fed a control or high methionine/low folate (HH) diet during pregnancy. The F1 hybrid offspring were then fed the control or HH diet from weaning for 6 weeks. Independent of prenatal diet, Cbs +/‐ x Cast mice fed the post‐weaning HH diet had higher ( P <0.001) plasma homocysteine than Cbs +/+ x Cast mice fed the control diet. This was accompanied by higher ( P <0.05) S ‐adenosylhomocysteine (SAH), lower (P<0.01) S ‐adenosylmethionine/SAH ratios, and lower ( P <0.01) Igf2 mRNA in brain. Mice exposed to the prenatal and post‐weaning HH diet had higher ( P =0.05) H19 mRNA, lower H19 / Igf2 mRNA ratios, and higher ( P <0.05) paternal and maternal allele DMD methylation in brain than mice not exposed to the prenatal HH diet. These findings show that prenatal exposure to disrupted maternal methyl metabolism is associated with differential methylation and expression of H19/Igf2 and suggests a role for methyl metabolism in metabolic programming. Grant Funding Source CIHR/Sick Kids Foundation, Heart & Stroke Foundation
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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 | 0.001 |
| 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".