Abstract 218: Age Impacts Circulating Testosterone Levels in Male Intrauterine Growth Restricted Rats Leading to Glucose Intolerance and Alterations in Programmed Hypertension

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Low birth weight increases the risk for hypertension, obesity, and impaired insulin and glucose metabolism in later life. We previously reported that reduced uterine perfusion induced at day 14 of gestation in the pregnant rat leads to intrauterine growth restriction (IUGR) and programs testosterone dependent hypertension at 4 months of age in male IUGR offspring relative to male control. Whether age impacts chronic health in male IUGR is unknown. Thus, the aim of this study was to test the hypothesis that age impacts cardiovascular and metabolic health in male IUGR offspring. Male control and male IUGR offspring were studied at 6 and 12 months of age. Mean arterial pressure (MAP) measured in conscious, chronically instrumented animals via arterial catheter was significantly increased in IUGR at 6 months of age (138.9±2 mmHg, n=9; P<0.05) relative to age-matched control (127.4±4 mmHg, n=9). However, blood pressure was not significantly elevated at 12 months of age (IUGR: 142.9±4 mmHg, n=10 versus control: 136.7±2 mmHg, n=6). Glucose tolerance was maintained in IUGR at 6 months of age versus age-matched control as demonstrated by area under the curve (AUC) (456.2±28, n=7 versus 436.6±14, n=11; respectively). However, glucose tolerance was impaired in IUGR at 12 months of age (509.1±18, n=10; P<0.05) versus age-matched control (437.2±13 AUC, n=9). Insulin tolerance and insulin release in response to an oral glucose challenge were similar in IUGR and control at 12 months of age. Age-dependent increases in body weight, visceral fat, and total fat mass were also similar and 24 hour food intake and water intake did not differ at 12 months of age. Testosterone deficiency is reported to be associated with impaired metabolic health. In this study, circulating testosterone remained markedly higher in IUGR (448.9±156 ng/dl; P<0.05) at 6 months of age relative to male control (152.2±17 ng/dl); yet, was no longer significantly elevated at 12 months of age (IUGR: 256.6±40 versus control: 177.4±18 ng/dl). Thus, these findings indicate that male IUGR offspring exhibit glucose intolerance and a loss of programmed hypertension at 12 months of age that may be due to an age-dependent decrease in testosterone. Future studies are needed to investigate the exact underlying mechanisms.

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