No conflicts of interest were declared.
Haem oxygenase-1 dictates intrauterine fetal survival in mice via carbon monoxide†
Article first published online: 8 JUL 2011
Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 225, Issue 2, pages 293–304, October 2011
How to Cite
Zenclussen, M. L., Casalis, P. A., El-Mousleh, T., Rebelo, S., Langwisch, S., Linzke, N., Volk, H.-D., Fest, S., Soares, M. P. and Zenclussen, A. C. (2011), Haem oxygenase-1 dictates intrauterine fetal survival in mice via carbon monoxide. J. Pathol., 225: 293–304. doi: 10.1002/path.2946
- Issue published online: 6 SEP 2011
- Article first published online: 8 JUL 2011
- Accepted manuscript online: 30 MAY 2011 08:13AM EST
- Manuscript Accepted: 25 MAY 2011
- Manuscript Revised: 18 MAY 2011
- Manuscript Received: 13 JAN 2011
- haem oxygenase;
- carbon monoxide;
- intrauterine growth restriction
Pregnancy establishment implies the existence of a highly vascularized and transient organ, the placenta, which ensures oxygen supply to the fetus via haemoproteins. Haem metabolism, including its catabolism by haem oxygenase-1 (HO-1), should be of importance in maintaining the homeostasis of haemoproteins and controlling the deleterious effects associated with haem release from maternal or fetal haemoglobins, thus ensuring placental function and fetal development. We demonstrate that HO-1 expression is essential to promote placental function and fetal development, thus determining the success of pregnancy. Hmox1 deletion in mice has pathological consequences for pregnancy, namely suboptimal placentation followed by intrauterine fetal growth restriction (IUGR) and fetal lethality. These pathological effects can be mimicked by administration of exogenous haem in wild-type mice. Fetal and maternal HO-1 is required to prevent post-implantation fetal loss through a mechanism that acts independently of maternal adaptive immunity and hormones. The protective HO-1 effects on placentation and fetal growth can be mimicked by the exogenous administration of carbon monoxide (CO), a product of haem catabolism by HO-1 that restores placentation and fetal growth. In a clinical relevant model of IUGR, CO reduces the levels of free haem in circulation and prevents fetal death. We unravel a novel physiological role for HO-1/CO in sustaining pregnancy which aids in understanding the biology of pregnancy and reveals a promising therapeutic application in the treatment of pregnancy pathologies. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.