Abstract 853: The effect of maternal folic acid supplementation during pregnancy and lactation on global DNA methylation in the offspring
Notice bibliographique
Résumé
Abstract Background: Folate plays an essential role in biological methylation reactions including that of DNA, aberrations of which have been shown to be mechanistically related to cancer. Intrauterine and early life exposure to folic acid has significantly increased in North America due to mandatory folic acid fortification, widespread supplemental use and periconceptional supplementation. Epigenetic programming occurs during embryogenesis and hence the embryonic stage is highly susceptible to changes in the intrauterine environment, which may influence the risk of developing cancer in adulthood. Although maternal supplementation of methyl group donors has been shown to influence DNA methylation in the offspring, the effect of maternal folic acid supplementation alone on DNA methylation in the offspring is not well established. We therefore investigated the effect of maternal folic acid supplementation provided during pregnancy and lactation on global DNA methylation in the offspring. Methods: Female C57BL/6 mice were placed on amino acid defined diets containing 2 (control), 5, 8, or 25 mg folic acid/kg diet for 3 weeks prior to mating and throughout pregnancy and lactation. At weaning (3 weeks of age), 20 pups from each maternal diet were killed. The remaining pups (20 from each maternal diet group) were placed on the control diet until they were killed at 18 weeks of age. Plasma and liver folate concentrations were determined at 3 and 18 weeks of age. Global DNA methylation was determined in the liver at both time points using the in vitro methyl-acceptance assay. Results: At weaning, pups from the 5, 8, and 25 mg folic acid/kg supplemented maternal diets had significantly higher plasma and liver folate concentrations compared with those from the control maternal diet in a dose-responsive manner (p<0.05). At 18 weeks of age, plasma folate concentrations in pups from the 8 and 25 mg folic acid/kg supplemented maternal diets remained significantly higher than those of pups from the control maternal diet (p<0.05), while liver folate concentrations did not differ significantly among pups from the four maternal diet groups. At both time points, hepatic global DNA methylation was significantly lower in pups from mothers on the folic acid supplemented diets compared with pups from the maternal control diet (p<0.05). Although no clear dose-dependence was observed, 25 mg folic acid/kg maternal diet produced the greatest magnitude of decrease in global DNA methylation in pups at both time points. Conclusion: Our data suggest that maternal folic acid provided during pregnancy and lactation can induce global DNA hypomethylation in the offspring, and that this effect appears to persist into adulthood. The functional ramifications of the observed global DNA hypomethylation as well as its potential mechanistic link to cancer risk in the offspring need to be determined in future studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 853. doi:10.1158/1538-7445.AM2011-853
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».