Erythropoietin gene expression in fetal and adult sheep kidney

The exact location of the cells which express erythropoietin (Epo) in the kidney is still controversial, with conflicting reports suggesting that both peritubular interstitial cells or proximal tubular epithelial cells are possible sites of Epo expression. In the present study we have examined the location of Epo-expressing cells in fetal and adult sheep kidneys after Epo expression was stimulated by anaemia. In situ hybridization histochemistry was performed using synthetic oligonucleotide probes complementary to part of the sheep Epo cDNA sequence or a riboprobe (cRNA) for ovine Epo of 520 bases. Epo expression was confined to peritubular cells of the kidney cortex, in general in the area close to the cortico-medullary junction. In some severely anaemic adult sheep kidneys, Epo-expressing cells were also found in the outer cortex. In addition we located Epo-expressing cells in the kidneys not only of anaemic fetuses (89-140 d of gestation, term = 150d) but also in kidneys from normal fetuses 60-110d of gestation. Again, Epo expression was seen only in peritubular cells of the kidney cortex. These findings confirm that the kidney is an important site of Epo production, in the sheep, from at least 0.4 gestation, but also show that there is no ontogenic change in the cellular site of production within the kidney.