Maternal Copper Deficiency Perpetuates Altered Vascular Function in Sprague-Dawley Rat Offspring

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

Submitted to: Journal of Developmental Origins of Health and Disease
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/11/2010
Publication Date: 2/11/2010
Citation: Anderson, C.M., Johnson, W.T. 2010. Maternal Copper Deficiency Perpetuates Altered Vascular Function in Sprague-Dawley Rat Offspring. Journal of Developmental Origins of Health and Disease. 1(2):131-140.

Interpretive Summary: Estimates of usual copper intakes from food indicate that up to 90% of pregnant women and up to 95% of lactating women do not meet either the estimated average requirement (EAR) or recommended dietary allowance (RDA) for copper. These results indicate that copper intakes below the EAR and RDA are not uncommon for pregnant and lactating women. It is known that copper deficiency can influence blood pressure by altering vascular responses to signals that regulate blood pressure. It is also known that maternal nutrition during pregnancy and lactation is a determinant for the development of disease in offspring. However, it is not known whether low copper intake during pregnancy and lactation increases the risk for cardiovascular disease in offspring. This study shows that low copper intake during pregnancy and lactation in rats alters the way blood vessels respond to signals that regulate blood pressure in offspring even though the offspring are not copper-deficient. Furthermore, the offspring of the first generation offspring whose mothers had low copper intake during pregnancy and lactation also showed signs of altered vascular signaling. This indicates that adequate copper intake during pregnancy is essential for the development of vascular signaling pathways in offspring and that low copper intake during pregnancy causes persistent changes in vascular responses that may increase the risk for cardiovascular disease across several generations.

Technical Abstract: Little is known about the consequences of maternal Cu (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 Cu-deficient Sprague-Dawley rat dams and from offspring directly exposed to maternal Cu deficiency during development and lactation and perpetuation of the effects in a second generation of offspring. Dams were fed a diet with 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. At reproductive maturity, F1 pairs were bred within groups resulting in second generation (F2) offspring. At nine weeks of age, mesenteric artery (200'm) isometric tension was determined in response to vasoconstrictors and vasorelaxants using a small wire myograph. Cu deficiency did not alter vascular function in dams. In F1 offspring, increased responsiveness to KCl was due to direct exposure to maternal Cu deficiency in the birth mother, while enhanced endothelial dependent and independent relaxation responses resulted from postnatal exposure to maternal Cu deficiency. Enhanced responses to phenylephrine and acetylcholine was seen among F2 female offspring born to F1 dams whose mothers were exposured to Cu deficiency, and enhanced responsiveness to sodium nitroprusside among those born to F1 dams whose mothers were exposed to Cu deficiency. These data indicate that exposure to maternal Cu deficiency during critical windows of development alter vascular function and that alterations are propagated in a sex-dependent manner.