Therapeutic Strategy for Recurrent Spontaneous Abortion

DESCRIPTION (provided by applicant): Recurrent spontaneous abortion (RSA) is a serious medical condition that affects approximately 1-3% of reproductive age women. At present, there is no FDA approved treatment for RSA. We hypothesize that failure to suppress Th1 cytokine production early in pregnancy is a major cause of RSA. We hypothesize that recombinant human granulocyte colony stimulating factor (rhG-CSF) will prevent RSA caused by Th1 cytokine overproduction because rhG-CSF is known to cause an orchestrated shift from Th1 to Th2 cytokine predominance. Th2 cytokine predominance is associated with successful pregnancy outcome. In the current application, we propose to evaluate rhG-CSF as a treatment for RSA in a widely used mouse model of spontaneous abortion. Specifically, we plan to: 1. Test the hypothesis that rhG-CSF administered to CBA female mice at the time of conception will prevent spontaneous abortion. 2. To test the hypothesis that the protective effect of G-CSF against miscarriage is mediated by changes in the immune system as opposed to changes in the decidua and the placenta, where G-CSF and its receptor are normally expressed during pregnancy. Successful completion of the experiments described in this application will pave the way for a future human trial of rhG-CSF for the treatment of RSA.