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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Healthy Body Weight Research » Research » Publications at this Location » Publication #242408

Title: Maternal Copper Deficiency Perpetuates Altered Vascular Function Across Two Generations of Sprague-Dawley Rat Offspring

item ANDERSON, CINDY - University Of North Dakota
item Johnson, William

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 8/1/2009
Publication Date: 11/25/2009
Citation: Anderson, C.M., Johnson, W.T. 2009. Maternal Copper Deficiency Perpetuates Altered Vascular Function Across Two Generations of Sprague-Dawley Rat Offspring. [Meeting Abstract]. Journal of Developmental Origins of Health and Disease (Vol. 1 Suppl 1).

Interpretive Summary:

Technical Abstract: Objective: Several studies provide evidence of impaired macronutrient availability on future disease and highlight the tissue-specificity and timing of the nutritional insult on adult phenotype, though less is known about the long-term effects of micronutrient deficiencies. Further, little is known about the consequences of maternal copper (Cu) deficiency on the vascular function of offspring or on perpetuation of vascular effects to a second generation. We examined vascular functional responses in mesenteric arteries from copper deficient Sprague-Dawley rat dams and from offspring directly exposed to maternal copper deficiency during development and lactation and perpetuation of the effects in a second generation of offspring. Methods: Dams were fed an AIN-93 G diet formulated with CuSO4•5H20 to contain either marginal (1 mg Cu/kg) or adequate (6 mg Cu/kg) Cu 3 weeks prior to conception and throughout pregnancy and lactation periods. Half of the first generation (F1) litters were cross-fostered. F1 pairs were bred within groups resulting in second generation (F2) offspring. Offspring were fed a diet adequate in copper after weaning. Hepatic Cu concentrations were analyzed by atomic absorption spectroscopy in dams and F1 male and female pups at weaning and repeated at 9 weeks in F1 offspring. Plasma ceruloplasmin activity was determined in dams and offspring at time of hepatic Cu measurement. Mesenteric artery (200'm) isometric tension was determined in response to vasoconstrictors and vasorelaxants using a small wire myograph at weaning in dams and at nine weeks of age in offspring. Approval obtained from the Animal Care and Use Committee of the GFHNRC in accordance with National Research Council Guidelines. Results: At weaning, dams fed the Cu deficient diet had significantly lower liver Cu concentrations and ceruloplasmin activities compared to dams consuming Cu adequate diet. Hepatic Cu concentrations were significantly lower on in F1 offspring postnatal day 21, the effect limited to those born to dams on the Cu deficient diet. At 9 weeks of age, no differences in F1 Cu status were evident. Cu deficiency did not alter vascular function in dams. In F1 offspring, increased responsiveness to potassium chloride in male offspring was due to direct exposure to maternal copper deficiency in the birth mother, while enhanced endothelial dependent and independent relaxation responses in female offspring resulted from postnatal and combined in-utero and postnatal exposure to maternal copper deficiency, respectively. Altered relaxation responses were perpetuated to a second generation of male offspring, consistent with the maternal F1 phenotype. Conclusions: Low hepatic Cu concentrations in offspring of dams fed Cu-deficient diet were established prenatally and were not readily reversed by allowing the offspring to suckle dams that were fed Cu-adequate diet. As F1 dams and sires were copper replete at the time of conception and F2 offspring were not subjected to dietary intervention, alterations in F2 vascular function represent the influence of the persistence of F1 exposure to prenatal and/or postnatal maternal Cu deficiency. These data indicate that exposure to maternal Cu deficiency during critical windows of development alter vascular function which are propagated to a second generation of offspring.