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Altered Health Outcomes in Adult Offspring of Sprague Dawley and Wistar Rats Undernourished During Early or Late Pregnancy
Citation:
Ellis-Hutchings, R. G., R. M. ZUCKER, B. E. GREY, J. NORWOOD, J. E. RICHARDS, C. LAU, AND J. M. ROGERS. Altered Health Outcomes in Adult Offspring of Sprague Dawley and Wistar Rats Undernourished During Early or Late Pregnancy. BIRTH DEFECTS RESEARCH PART B: DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY. John Wiley & Sons, Ltd., Indianapolis, IN, 89(5):396-407, (2010).
Impact/Purpose:
This paper reports the effects of gestational undernourishment on adult health of offspring. Notable effect is that offspring of undernourished mothers had higher blood pressure than control offspring. Effects on kidney development likely play a role in this effect.
Description:
Gestational undernutrition in humans can result in birth weight reductions (an indicator of a suboptimal intrauterine environment) and predisposition to adult disease in offspring including high blood pressure, insulin resistance, glucose intolerance, and obesity (key components of metabolic syndrome). Maternal undernutrition is a common finding during chemical safety testing studies in rats, with the long-term effects largely unknown. Animal models have recapitulated some of the human findings, although results have varied depending on the species and strain of animal and period of deprivation utilized. This study was designed to compare alterations in metabolic syndrome components following 50% global undernutrition (feed restriction) on gestation days (GD) 1-15 (UNI-15) or GD 10-21 (UNI0-21), in Sprague Dawley and Wistar rats. Control rats were fed chow diet ad libitum throughout pregnancy. Offspring from food-deprived dams were cross-fostered to control dams at birth and litters standardized to 8 pups (4 per sex). At weaning, male pups were fed either a control diet (10% fat-derived calories) or a high fat diet (35% fat-derived calories). Young (postnatal week (PNW) 10-11) and mature adult (PNW 26-28) offspring were evaluated for body weight and/or fat depot weights, blood pressure (BP), glucose/insulin response to oral glucose challenge, and an atherogenic serum lipid profile. Nephron endowment, renal glucocorticoid receptor and renin-aldosterone-angiotensin system (RAS) components were evaluated as putative factors in elevated blood pressure. The UN 10-21 group of both strains had birth weights lower than controls and, transient catchup growth by weaning. In neither strain was dyslipidemia, obesity or increased fat depot weights associated with prenatal undernourishment. On the contrary, long term body weight deficits occurred in both UN groups of both strains. Weanlings fed the high fat diet gained more weight than those fed the control diet, but there was no interaction with prenatal nutritional status. Compared to the Wistar strain, the Sprague Dawley strain was slightly more susceptible to altered insulin responsiveness and increased BP following gestational undernutrition. The Wistar strain exhibited a later onset of elevated (BP) than did the Sprague Dawley strain, with increases evidentat 26 weeks of age compared to 10weeks of age in the Sprague Dawley strain. Nephron endowment in Sprague Dawley, but not Wistar off spring, was lower in the UNI0-21 groups. The glucocorticoid and RAS pathways were not altered. In conclusion, the strongest effect of maternal undernutrition was elevated blood pressure in offspring. Notably, we did not observe obesity in offspring of any group. Sprague Dawley rats were slightly, more sensitive than the Wistar strain for effects on BP and nephron endowment. Long-term health effects occured with undernutrition during either window examined in this study, but the UNI0-21 period resulted in lower birth weight and more severe effects later in life.
