Marginal copper deficiency in pregnancy: Vascular responses in dams and progeny

Authors: ANDERSON, CINDY - UNIV OF NORTH DAKOTA; Johnson, William

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 5/15/2007
Publication Date: 8/30/2007
Citation: Anderson, C.M., Johnson, W.T. 2007. Marginal copper deficiency in pregnancy: Vascular responses in dams and progeny. [abstract] Presented at Aspen Perinatal Biology Symposium, August 25-28, 2007, Aspen, CO. Abstracts were not published.

Interpretive Summary:

Technical Abstract: Objectives: Copper (Cu) is essential in defense against oxidative stress and to development of connective tissue in the heart and blood vessels. The long-term effects of marginal Cu deficiency on vascular function during pregnancy have not been characterized previously. In this study, the vascular consequences of marginal Cu deficiency were determined by measurement of contractile and relaxation responses in mesenteric arteries of dams and their offspring. Residual effects perpetuated to a subsequent generation of offspring were determined in progeny of dams and sires with intrauterine exposure to marginal Cu deficiency during development and/or lactation. Methods: Pregnant dams were fed an AIN93G diet beginning 3 weeks before conception and remained on the diet throughout lactation until postnatal day (PND) 21. Dams consuming diets containing 1 mg Cu/kg were marginally Cu deficient (CuD; n=7); dams fed a diet containing 6 mg Cu/kg served as controls (CuA; n=8). To define the critical developmental window, 50 percent of pups born to CuD dams were cross-fostered to CuA dams and vice versa on PND 1. Pups that were born to and remained with their CuD birth mothers until weaning were considered CuD first generation (F1) offspring; pups born to and remaining with Cu adequate birth mothers served as CuA F1 controls. After weaning, all offspring were transitioned to rat chow containing adequate amounts of Cu. At reproductive maturity, F1 offspring were mated within groups to determine perpetuation of vascular effects resulting from Cu deficiency in a second generation (F2). A small wire myograph was used to determine mesenteric arterial responses to vasoconstrictors (phenylephrine [PE], potassium chloride [KCl]) and endothelium-dependent and -independent relaxants (acetylcholine [ACh]) and sodium nitroprusside [SNP], respectively) in dams on PND 21 and in offspring groups at 9 weeks of age (n=5-7/group). Group differences were determined by students t test or ANOVA with Tukey post hoc with a level of <0.05 considered significant. Results: There were no significant differences in vasoconstrictor or vasorelaxant responses in dams. Among F1 male offspring, vasoconstrictor responsiveness to KCl was increased when Cu deficiency was limited to the lactation period (p<0.05). Relaxation responses were impaired among female F1 offspring with Cu deficiency limited to lactation, as compared to deficiency during both intrauterine development and lactation (endothelium-dependent and independent, p<0.05), to offspring with intrauterine exposure to Cu deficiency coupled with adequate Cu during lactation (endothelium-dependent, p<0.05); and to control (endothelium-independent, p<0.05). Among F2 offspring, there were no differences in vasoconstrictor or vasorelaxant responsiveness between groups. Conclusions: Cu deficiency during early postnatal nutrition leads to altered mesenteric artery responsiveness in a gender-specific manner. Alterations in vascular function were not perpetuated to a second generation of offspring.