Gestational intermittent hypoxia induces endothelial dysfunction, reduces perivascular adiponectin and causes epigenetic changes in adult male offspring
Notice bibliographique
Résumé
Key points Obstructive sleep apnoea (OSA) is characterized by intermittent hypoxia, which causes oxidative stress and inflammation and increases the risk of cardiovascular disease. OSA during pregnancy causes adverse maternal and fetal outcomes. The effects of pre‐existing OSA in pregnant women on cardiometabolic outcomes in the offspring are unknown. We evaluated basic metabolic parameters, as well as aortic vascular and perivascular adipose tissue (PVAT) function in response to adiponectin, and examined DNA methylation of adiponectin gene promoter in PVAT in 16‐week‐old adult offspring exposed to gestational intermittent hypoxia (GIH). GIH decreased body weights at week 1 in both male and female offspring, and caused subsequent increases in body weight and food consumption in male offspring only. Adult female offspring had normal levels of lipids, glucose and insulin, with no endothelial dysfunction. Adult male offspring exhibited dyslipidaemia, insulin resistance and hyperleptinaemia. Decreased endothelial‐dependent vasodilatation, loss of anti‐contractile activity of PVAT and low circulating PVAT adiponectin levels, as well as increased pro‐inflammatory gene expression and DNA methylation of adiponectin gene promoter, occurred in adult male offspring. Our results suggest that male offspring of women with OSA could be at risk of developing cardiometabolic disease during adulthood. Abstract Perturbations during pregnancy can program the offspring to develop cardiometabolic diseases later in life. Obstructive sleep apnoea (OSA) is a chronic condition that frequently affects pregnancies and leads to adverse fetal outcomes. We assessed the offspring of female mice experiencing gestational intermittent hypoxia (GIH), a hallmark of OSA, for changes in metabolic profiles, aortic nitric oxide (NO)‐dependent relaxations, perivascular adipose tissue (PVAT) anti‐contractile activities and the responses to adiponectin, and DNA methylation of the adiponectin gene promoter in PVAT tissue. Pregnant mouse dams were exposed to intermittent hypoxic cycles ( 21–12%) for 18 days. GIH resulted in lower body weights of pups at week 1, followed by significant weight gain by week 16 of age in male but not female offspring. Plasma lipids, leptin and insulin resistance were higher in GIH male adult offspring. Endothelium‐dependent relaxation in response to ACh and the anti‐contractile activity of PVAT in the abdominal aorta was reduced in GIH adult male offspring. Incubation of arteries from GIH adult male offspring with adiponectin restored the anti‐contractile activity of PVAT. Both circulating and PVAT tissue homogenate levels of adiponectin, as well as gene expression of adiponectin in PVAT, were lower in GIH male offspring, along with an increased gene expression of inflammatory cytokines. Pyrosequencing of adiponectin gene promoter in PVAT showed increased DNA methylation in GIH male offspring. Our results indicate that GIH leads to vascular disease in adult male offspring through PVAT dysfunction, which was associated with low adiponectin levels and epigenetic modifications on the adiponectin gene promoter.
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 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 | 0,000 | 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 | 0,000 |
| 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 ».