Embryonic, Fetal,and Neonatal Hemoglobin Synthesis: Relationship to Abortion and Thalassemia.

摘要

In the embryo and fetus,the events and genetic mechanisms regulating the production of the five different globin chains account for several molecular species of intrauterine and neonatal hemoglobins. Strikingly intricate,synchronized correlations with reference to onset,peak level,and disappearance of: (1) five distinct globin chains; (2) five molecular species of hemoglobin; (3) three distinct intrauterine erythropoietic cell lines;ad (4) erythropoiesis in three specific embryonic and fetal organs are noted and result in new insights and findings. It is shown on the basis of correlated published data in the literature that under normal conditions of embryonic and fetal hemoglobin synthesis: (1) the erythroblasts in the yolk sac in the first trimester synthesize alpha and epsilon globin chains and so produce hemoglobins Gower-1and Gower-2; (2) the erythroblasts in the liver in the second trimester synthesize alpha and gamma globin chains predominantly and so produce hemoglobin F;and (3) the erythroblasts in the bone marrow in the second trimester initially and in the third trimester more intensely synthesize alpha,beta,and delta globin chains and so produce hemoglobins A and A2predominantly. Important clinical insights are gained by an understanding of these genetic,biochemical,and embryologic correlations of intrauterine erythropoiesis,including the basis: (1) for the well-known but presently unexplained peak incidence of abortions at the end of the first trimester; (2) for the delayed postnatal morphologic expression of S hemoglobin; (3) for the appearance of hemoglobinopathies Bart's and H;and (4) for the thalassemia syndromes. (Author)