Serum copper levels in pregnancy and in pre-eclampsia.

In 1928 Krebs reported that the concentration of copper in the serum was significantly raised in the terminal stages of pregnancy. Since that time this observation has been confirmed by a number of workers (Gorter, Grendel, and Weyers, 1931; Locke, Main, and Rosbash, 1932; Sachs, Levine, and Fabian, 1935; Nielsen, 1944), who have shown that at full term the serum copper level is approximately twice the value found in non-pregnant subjects. The significance of this raised serum copper level in pregnancy is, however, still obscure. Sachs, Levine, and Fabian (1935) have concluded that it represents a normal, physiological adjustment for the transport of copper from the maternal blood to the foetus, but no evidence is presented in support of this view. Other observations in the literature suggest that the hypercupraemia of pregnancy may, in part at least, be associated with some more specific function. It is well established that certain of the plant phenol oxidases are copper-containing proteins (Kubowitz, 1937, 1938; Keilin and Mann, 1938, 1939). Baker and Nelson (1943) have described a copper protein from kidney which is capable of catalysing the oxidation of adrenaline, and Holmberg in 1944 obtainedc a blue coppercontaining protein from the "euglobulin" fraction of the serum proteins which possessed a laccase-like activity, catalysing the oxidation of p-phenylenediamine. -More recently, Holmberg and Laurell (1948) have described a blue protein containing 0.36% Cu derived from the serum globulin fraction which, when added to male plasma to give a final copper concentration of 700 ,ug. /100 ml., increased the histaminolytic activity of the plasma 400-fold. They also point out that the increase in serum copper in pregnancy runs parallel with the increase in the histaminolytic activity of the plasma. In view of this finding, and since changes in the histaminolytic activity of the plasma have been reported in pre-eclamptic toxaemia (KapellerAdler, 1944, 1947), a study of the level of serum copper in this condition has been carried out. It is known from the work of Abderhalden and Moller (1928) and Boyden and Potter (1937) that the copper in the plasma from non-pregnant subjects exists in a non-dialysable form, and Eisler, Rosdahl, and Theorell (1936), using electrophoretic methods, have stated that the rate of migration of the copper in horse serum is the same as that of the serum albumin. Cohn and Koechlin (1947), on the other hand, have described a copper-combining protein in the ,-globulin fraction of human plasma. Experiments have also been carried out therefore to determine the proportion of the copper precipitating with various protein fractions, separated by graded concentrations of sodium sulphate, from the serum of both non-pregnant and pregnant subjects.