Gestational intermittent hypoxia induces endothelial dysfunction, reduces perivascular adiponectin and causes epigenetic changes in adult male offspring.
Mohammad BadranBisher Abu YassinDavid Tse Shen LinMichael S KoborNajib AyasIsmail LaherPublished in: The Journal of physiology (2019)
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 ( F I O 2 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.
Keyphrases
- high fat diet
- insulin resistance
- dna methylation
- gene expression
- adipose tissue
- metabolic syndrome
- weight gain
- genome wide
- skeletal muscle
- nitric oxide
- high fat diet induced
- copy number
- type diabetes
- polycystic ovary syndrome
- pregnant women
- obstructive sleep apnea
- body mass index
- heart failure
- emergency department
- endothelial cells
- randomized controlled trial
- birth weight
- aortic valve
- physical activity
- oxidative stress
- childhood cancer
- depressive symptoms
- smooth muscle
- atrial fibrillation
- preterm birth
- nitric oxide synthase