HIGH MATERNAL SERUM CHORIONIC-GONADOTROPIN LEVEL IN DOWNS-SYNDROME PREGNANCIES IS CAUSED BY ELEVATION OF BOTH SUBUNITS MESSENGER-RIBONUCLEIC-ACID LEVEL IN TROPHOBLASTS

A unique product of human placenta is CG. Its concentration in materna l blood rises exponentially until 9-10 weeks' gestation, thereafter, i t decreases to about 20% of the maximum, remaining constant from 16-17 until 40 weeks. High second-trimester maternal blood level indicates an increased risk for Downs' Syndrome (DS). This study's aim was to de termine whether changes occur in the genetic expression of CG subunits in cultured trisomy-21 trophoblasts compared with various gestational age controls. Second-trimester trisomy-21 trophoblasts secrete 10 tim es more CG than gestational age-matched controls during the first day in culture: 878 (range, 235-2230) IU/g vs. 87 (range, 20-150) IU/g (P < 0.05). This high secretion closely resembles quantities secreted by first-trimester normal trophoblasts: 7500 (range, 3,850-10,000) IU/g. Both subunits' messenger RNA content are substantially increased, CG b eta much more than CG alpha, although these genes are not located on c hromosome 21. We conclude that at least one cause of high second-trime ster maternal blood CG in DS pregnancies is a rise in alpha and beta C G messenger RNA levels in the trophoblast. We propose that at 12-14 we eks, when rapid decrease in maternal blood CG levels can be found, hig her than normal values may indicate an increased risk for DS.