EFFECTS OF PERINATAL ZIDOVUDINE ON HEMATOPOIESIS - A COMPARISON OF EFFECTS ON PROGENITORS FROM HUMAN FETUSES VERSUS MOTHERS

Objective: To compare the effects of zidovudine (ZDV) on clonal matura tion of hematopoietic progenitors obtained from the bone marrow of wom en of child-bearing age with its effects on progenitors obtained from the marrow, liver and blood of fetuses. We also sought to determine wh ether the adverse effects of ZDV on fetal hematopoiesis resulted exclu sively from an action on progenitors, or also involved the inhibition of the production of hematopoietic growth factors. Participants: Hemat opoietic progenitors were obtained from bone-marrow aspirates of seven women of child-bearing age, from the bone marrow and liver of seven m idtrimester abortuses, and from the umbilical cord blood of seven term infants. Methods: We added increasing concentrations of ZDV to clonal assays of hematopoietic progenitors, after which we assayed clonal ma turation of progenitors, and counted the number of erythrocytes per er ythroid clone and the number of neutrophils per granulocytic clone. Li ght-density cell fractions and enriched CD34+ progenitor fractions wer e studied. In other studies we determined the effect of increasing con centrations of ZDV on production of granulocyte colony-stimulating fac tor (G-CSF) protein [enzyme-linked immunosorbent assay (ELISA)] and mR NA by fetal and maternal monocytes, and on production of erythropoieti n protein (ELISA) and mRNA by Hep3 B cells. Results: Mature erythroid progenitors were the most sensitive to the adverse effects of ZDV on c lonal maturation, and multipotent progenitors were the most resistant. Erythroid progenitors from all fetal and neonatal sources were more s ensitive to the effect of ZDV than those from the bone marrow of adult women. The inhibitory effects were explained by an action on CD34+ ce lls; no effect was observed on production of G-CSF or erythropoietin. Conclusions: We speculate that the low hematocrits of neonates deliver ed after antenatal ZDV treatment are due to reduced clonal maturation of erythroid progenitors, and that fetal erythroid progenitors are inh ibited to a greater extent than maternal progenitors.