Prenatal Chronic Hypoxia in Rats Leads to Insulin Resistance and Hypertension in Adult Offspring

Abstract

Abstract Background To investigate the effects of chronic intrauterine hypoxia on insulin resistance, hypertension, and the correlation between them in adult offspring rats. Methods A total of 25 pregnant Sprague Dawley rats were randomly assigned into 4 prenatal chronic hypoxia (H) groups (10% ± 1% oxygen) and a control group (21% oxygen). The H groups were divided into whole (1–21 day), early (1–7 day), mid (8–14 day), and late (15–21 day) gestational hypoxia groups (H1, H2, H3, and H4, respectively) with pregnant rats being housed in a hypoxia box for 3 hours per day. Five male and 5 female offspring in each group were studied at 1 day, 3 months, and 6 months old. Blood pressure, fasting blood glucose, fasting serum insulin, and insulin resistance index were determined. Results The mean blood pressure of offspring rats in H groups was higher at 3 months, and further increased at 6 months old compared to the control group (P < 0.05). The fasting blood glucose and homeostasis model insulin resistance index (HOMA-IR) of male and female offspring in the whole pregnancy (H1) and early pregnancy (H2) hypoxia groups were significantly higher than those in the control group at 6 months (P < 0.05). Fasting blood glucose and HOMA-IR were positively correlated with mean blood pressure (P < 0.05). The renal mass index in H2 group was lower at 3 months, and further decreased at 6 months compared to controls (P < 0.05). The mRNA and protein levels of insulin receptor, insulin receptor substrate (IRS-1 and IRS-2) in the kidneys in hypoxia groups were significantly decreased at 6 months in H1 and H2 hypoxia groups when compared with controls (P < 0.05). Conclusions Chronic intrauterine hypoxia causes insulin resistance and hypertension in adult offspring rats through poor intrauterine growth environment, and insulin resistance is positively associated with hypertension.