Folate Deficiency Alters the Sperm Epigenome and Reproductive Outcomes.
Notice bibliographique
Résumé
Data from epidemiological and animal studies suggests that the paternal epigenetic contribution in sperm may serve as a route to altered offspring phenotypes. However to date there is little to no evidence of direct effects of diets on the sperm epigenome or consequences for the offspring. Epigenetics refers to heritable changes in gene expression that are regulated by DNA methylation and the covalent modification of histones. Given that dietary folate can alter the supply of methyl donors, we hypothesized that male germ cells may be sensitive to dietary folate and that this may manifest as altered epigenetic programming and have downstream consequences for spermatogenesis and reproductive outcomes. The objective of this study was to determine the impact of exposure to a low folate diet, beginning during embryonic development through to adulthood on spermatogenesis, the sperm epigenome, fertility, and offspring. Inbred C57/BL6 mice were fed either a folate-sufficient (FS, 2 mg of folate/kg of diet), or a folate-deficient diet (FD, 0.3 mg of folate/kg of diet). Adult FS (n=54) and FD (n=49) males remained on the diets for either 2 or 4-4.5 months and were assessed for fertility parameters and overall health. In adults, spermatogenesis and sperm counts were not altered by diet nor were body, testis and epididymis weights. Epigenetic programming was disturbed in the sperm of folate depleted mice. Histone H3 methylation was significantly reduced in sperm from FD versus FS mice. Notably histone H3 methylation has been shown to mark genes for embryonic development. Genome wide DNA methylation (MeDIP-chip) analysis revealed alterations at more than 50 gene promoter regions. Bisulfite sequencing confirmed that 6 of these regions including genes implicated in developmental processes had significant decreases in DNA methylation at specific CpG locations in the sperm of FD males (n=5 for both groups). FD (n=29) and FS (n=27) males were then mated to females on control diets and pregnancy outcomes at embryonic day 18.5 were analyzed. Embryonic loss was 2 fold greater in the litters sired by FD vs FS mice and developmental abnormalities were observed in 27% of the litters sired by FD mice vs 3% for those sired by FS mice. This is the first study to show that diet can alter the sperm epigenome and suggests that an altered sperm epigenome leads to negative pregnancy outcomes. This research was supported by NSERC, and the Réseau Québécois en Reproduction (RQR-FQRNT).
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 tête enseignante, 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 ».