Hum. Reprod. Advance Access originally published online on January 23, 2008
Human Reproduction 2008 23(3):635-641; doi:10.1093/humrep/dem430
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Haemoglobin expression in human endometrium
1 Research Institute GROW, University Hospital Maastricht/University Maastricht, Peter Debyelaan 25, 6229 HX Maastricht, The Netherlands 2 Department of Pathology, University Hospital Maastricht/University Maastricht, Peter Debyelaan 25, 6229 HX Maastricht, The Netherlands 3 Department of Pharmacology, Organon N.V., Oss, The Netherlands 4 Department of Obstetrics and Gynaecology, University Hospital Maastricht/University Maastricht, Peter Debyelaan 25, 6229 HX Maastricht, The Netherlands 5 Present address: Department of Molecular Diagnostics, Philips Research, High Tech Campus 11, 5656 AE Eindhoven, The Netherlands 6 Present address: Department of Pharmacology, Organon N.V., PO Box 20, 5340 BH Oss, The Netherlands
7 Correspondence address. E-mail: g.dunselman{at}og.unimaas.nl (G.D.)
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 
, β, 
and 
and the haeme metabolizing enzyme, haeme oxygenase (HO)-1 in human endometrium.
METHODS: Using real-time quantitative PCR, haemoglobin , β, and , 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 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.
Key words: haemoglobin/haeme oxygenase/human endometrium/menstrual cycle/iron
Submitted on August 8, 2007; resubmitted on November 24, 2007; accepted on December 17, 2007.