Marginal copper deficiency impairs endothelium-dependent relaxation responses across two generations

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

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 11/15/2007
Publication Date: 4/15/2008
Citation: Anderson, C.M., Johnson, W.T. 2008. Marginal copper deficiency impairs endothelium-dependent relaxation responses across two generations [Abstract]. Journal of Federation of American Societies for Experimental Biology. 22:695.1.

Interpretive Summary: The generational effects of marginal copper (Cu) deficiency on vascular function have not been characterized.In this study, the vascular consequences of marginal Cu deficiency were determined by relaxation responses in mesenteric arteries of dams and two generations of offspring. Pups from dams (first generation, F1) fed AIN93G diet containing 1mgCu/kg (CuD) were cross fostered to dams fed diet with 6 mg Cu/kg (CuA) [3 weeks preconception through end of lactation] and vice versa on postnatal day (PND) 1.Control pups remained with their birth dams. After weaning, all F1 offspring were transitioned to CuA rat chow. F1 offspring were mated within groups to determine perpetuation of vascular effects from marginal Cu deficiency, resulting in second-generation offspring (F2). A small wire myograph was used to determine mesenteric arterial responses in dams on PND 21 and in F1 and F2 offspring groups at 9 weeks of age. There were no significant differences in relaxation responses in dams. In F1 offspring, CuD during lactation led to impaired endothelium-dependent relaxation. In F2 offspring, impaired endothelium-dependent relaxation occurred in male offspring born to dams with CuD in-utero. These findings indicate that future impairment of endothelium-dependent relaxation results from exposure to CuD during the critical developmental windows of lactation, propagated by CuD exposure in fetal development.

Technical Abstract: The generational effects of marginal copper (Cu) deficiency on vascular function have not been characterized.In this study, the vascular consequences of marginal Cu deficiency were determined by relaxation responses in mesenteric arteries of dams and two generations of offspring. Pups from dams (first generation, F1) fed AIN93G diet containing 1mgCu/kg (CuD) were cross fostered to dams fed diet with 6 mg Cu/kg (CuA) [3 weeks preconception through end of lactation] and vice versa on postnatal day (PND) 1.Control pups remained with their birth dams. After weaning, all F1 offspring were transitioned to CuA rat chow. F1 offspring were mated within groups to determine perpetuation of vascular effects from marginal Cu deficiency, resulting in second-generation offspring (F2). A small wire myograph was used to determine mesenteric arterial responses in dams on PND 21 and in F1 and F2 offspring groups at 9 weeks of age. There were no significant differences in relaxation responses in dams. In F1 offspring, CuD during lactation led to impaired endothelium-dependent relaxation. In F2 offspring, impaired endothelium-dependent relaxation occurred in male offspring born to dams with CuD in-utero. These findings indicate that future impairment of endothelium-dependent relaxation results from exposure to CuD during the critical developmental windows of lactation, propagated by CuD exposure in fetal development.