Assessment of the contribution of the spleen to granulocytopoiesis and erythropoiesis of the mid-gestation human fetus

Several current textbooks of hematology describe the spleen of the mid-gestation human fetus as a granulocytopoietic and an erythropoietic organ. Although studies in fetal rodents support this view, a convincing demonstration of such in normal human fetuses is lacking. We tested the hypothesis that the human mid-gestation fetal spleen is normally (1) a site of active granulocytopoiesis and erythropoiesis, or (2) a site of production of specific granulocytopoietic or erythropoietic growth factors. This was accomplished using the spleens, livers, and long-bones of 18 human fetuses, 13-22 weeks gestation, immediately following elective, induced, pregnancy terminations. Organs of some of the abortuses were placed directly into formalin for histologic evaluation. Organs from others were subjected to RNA extraction for subsequent probing for specific hematopoietic growth factor mRNA. Cell suspensions were created from the organs of other abortuses for quantification of the absolute number of neutrophils and erythrocytes and their precursors and progenitors. Evidence of active hematopoiesis was present in marrow and liver but not spleen. Transcripts for granulocyte colony-stimulating factor (G-CSF) were detected in the marrow but not the spleen or liver, and transcripts for erythropoietin (Epo) were detected in the liver but not the spleen or marrow. The populations of hematopoietic progenitor cells and normoblasts in the fetal spleen cell were similar to those in fetal blood. Thus, it is likely that the hematopoietic progenitors recovered from fetal spleen cell suspensions are the result of blood within the spleen, rather than from hematopoiesis within the organ. The spleen of mid-gestation human fetuses, unlike the spleen of fetal rats, does not normally function as an active site of granulocytopoiesis or erythropoiesis, nor is it an active site for production of G-CSF or Epo.