Ontogenetic expression of erythropoietin and hypoxia-inducible factor-1 alpha genes in subterranean blind mole rats

Blind subterranean mole rats of the Spalax ehrenbergi superspecies in Israel have evolved multiple adaptive strategies to face underground hypoxia. Hypoxia-inducible factor-1alpha ( HIF-1alpha) and erythropoietin (Epo) are key factors in the development of normal erythropoiesis and angiogenesis. Here, we demonstrate via real-time polymerase chain reaction (PCR) quantification that Spalax fetal liver and kidney express higher levels of Epo mRNA than Rattus, generating reinforcement of fetal erythropoiesis underground and adapting it to life underground in an atmosphere of abrupt and sharp fluctuations of O-2 supply. In neonates, Rattus liver and kidney express higher Epo levels than Spalax under both normoxia and hypoxia, probably due to Rattus ineffective erythropoiesis during embryonic life and its birth in a poorly ventilated breeding nest under ground. Adult Rattus kidney and liver, and adult Spalax liver express similar levels of Epo mRNA under normoxia and hypoxia. However, adult Spalax hypoxic kidney, the major site of erythropoietin production in adult mammals, shows levels that were twice as high as that of Rattus. Spalax expresses remarkably higher levels of HIF-1alpha mRNA than Rattus at all developmental stages studied, which peaked in neonates, as an adaptation against hypoxia.