The role of erythropoietin in prenatal erythropoiesis of congenitally anaemic flexed-tailed (f-f) mice.

Abstract

SummaryThe effects of the f gene on prenatal changes in liver cellularity, erythroid cell maturation, RNA, DNA, and haemoglobin synthesis, and sensitivity to erythropoietin have been investigated, f/f foetuses are smaller than f/+ but still develop a progressive deficiency in haemoglobin content/unit weight of tissue, which is 40% of normal at birth. Early f/f livers contain fewer erythroblasts, maximum numbers are reached later, and changes in relative proportions of early and late erythroblasts are retarded. Erythroid tissue and erythropoietin responsive cells persist longer in f/f than in f/+ livers. Erythropoietin induced RNA and DNA synthesis is higher in f/f than in f/+ foetal liver cell cultures. Erythropoietin causes multiphasic increments in haem synthesis in vitro. Maximum levels of synthesis by 13 day liver cells are reached later f/f but over 36 hr similar amounts are accumulated. Erythropoietin maintains the presence of early erythroid cells in both f/f and f/+ foetal liver cultures, and enhances the production of polychromatic cells.Circulating f/f foetal reticulocytes have a reduced capacity to utilize exogenous iron for haem synthesis. The deficient haemoglobin content of f/f foetuses could be caused by this abnormality and by reductions in erythroid precursor cell numbers. The reticulocyte abnormality may be a direct or indirect consequence of a failure of erythroid colonization of the foetal liver, and of the effects of secondary compensation for this failure.