Haemoglobin expression in human endometrium

BACKGROUND The general concept that haemoglobin is only a carrier protein for oxygen and carbon dioxide is challenged since recent studies have shown haemoglobin expression in non-erythroid cells and the protection of haemoglobin against oxidative and nitrosative stress. Using microarrays, we previously showed expression of haemoglobins α, β, δ and γ and the haeme metabolizing enzyme, haeme oxygenase (HO)-1 in human endometrium. METHODS Using real-time quantitative PCR, haemoglobin α, β, δ and γ, and HO-1 mRNA levels were assessed throughout the menstrual cycle (n = 30 women). Haemoglobin and HO-1 protein levels in the human endometrium were assessed with immunohistochemistry. For steroid responsiveness, menstrual and late proliferative-phase endometrial explants were cultured for 24 h in the presence of vehicle (0.1% ethanol), estradiol (17β-E2, 1 nM), progestin (Org 2058, 1 nM) or 17β-E2+Org 2058 (1 nM each). RESULTS All haemoglobins and the HO-1 were expressed in normal human endometrium. Haemoglobin mRNA and protein expression did not vary significantly during the menstrual cycle. Explant culture with Org 2058 or 17β-E2+Org 2058 increased haemoglobin γ mRNA expression (P < 0.05). HO-1 mRNA levels, and not protein levels, were significantly higher during the menstrual (M)-phase of the cycle (P < 0.05), and were down-regulated by Org 2058 in M-phase explants and by 17β-E2+Org 2058 in LP-phase explants, versus control (P < 0.05). CONCLUSIONS The haemoglobin-HO-1 system may be required to ensure adequate regulation of the bioavailability of haeme, iron and oxygen in human endometrium.