Study of the therapeutic potential of CO during implantation in a mouse model of spontaneous abortion
We have recently proposed a very important role for Heme Oxygenase-1 (HO-1) during pregnancy. Using animal models, we showed that immunological abortion is associated with decreased local levels of HO-1. Moreover, the up-regulation of HO-1 by Cobalt protoporphirin IX (Co-PP) application or gene therapy prevented abortion in mice. Further, we confirmed a HO-1 down-regulation/deficiency in samples from patients suffering from miscarriage. Interestingly, a well established microsatellite polymorphism of the HO-1 gene (leading to low levels of HO-1 expression) is associated with idiopathic recurrent miscarriage in humans. Knowing that the protective effect of HO-1 in other pathologies is mediated by one or several of its metabolite, we tested the effect of carbon monoxide (CO) in a murine model of abortion. Interestingly, our preliminary results clearly show that CO application exclusively during implantation (days 4 + 5 of pregnancy) is able to diminish the abortion rate but has deleterious effects if applied throughout pregnancy until day 13 (days 0-13 of pregnancy). However, CO is present in cigarette smoke and it is also known to be a toxic gas. Smoking during pregnancy has been shown to be deleterious for both, mother and baby but smoking before pregnancy (including implantation time) has no detrimental effects for pregnancy as no differences in pregnancy outcome can be observed between quitters once pregnancy was confirmed and non-smokers. The major aim of this application is to analyze the putative application of CO as a therapeutic gas in preventing abortion by establishing optimal doses and time frames of application in a murine model. Possible neurotoxic effects side effects of CO will be studied in both, mother and pups. The mechanisms beyond the putative protective effects of CO will be analyzed. Gaining data on this field might help developing novel and unexpected horizons in the therapy of pregnancy complications.