Background: Hypercoagulability plays an important role in recurrent abortion. We developed a plasminogen activator inhibitor (PAI-1) antagonist (Neuropharmacology 2010; 58: 972-80) that binds to tPA and inhibits its interaction with PAI-1, thereby increasing fibrinolysis.
Objective: To examine the role of PAI-1 in recurrent abortion in mice model of CBA/J (Females) X DBA/2 (Males).
Materials and methods: CBA/J female and DBA/2 male mice (purchased from Harlan Laboratories, Israel) were mated. Pregnancy day 0.5 was determined by the presence of a vaginal plug. CBA/J pregnant mice were euthanized on day 14.5 after. Resorbed and normal fetoplacental units were scored and the proportion of resorbed fetuses was evaluated: R% = 100 • Re/(Re+F) (Re: the number of resorbed embryos; F: the number of viable ones). Group 1 consisted of non-treated pregnant mice, group 2 was treated by an intra-peritoneal injection of saline and group 3 was treated twice daily with an intra-peritoneal injection of the antagonist (1mg/kg).
Results: The administration of PAI-1 significantly reduced the abortion rate. The R% in group 1(4 mice) was 30.3% (10 out of 33). In group 2 (3 mice) the R% was 27.8% (5 out of 18). The combined R% in the 2 control groups 1 and 2 was 29.4% (15 out of 51). In group 3 (5 mice) the R% was 13.9% (5 out of 36). The difference was statistically significant (P=0.02).
Conclusions: The results are very encouraging, should be confirmed in a larger scale experiment, and if found significant, may in the future be applied to humans.
Shani Ben Haroush1, Marwan Odeh1, Eilam Palzur2, Abd Al-Roof Higazi3, Jacob Bornstein1
Department of Obstetrics and Gynecology1 and Eliachar research Laboratory2 Western Galilee Hospital, Nahariya and, Department of Clinical Biochemistry, Hebrew University-Hadassah Medical Center, Jerusalem, Israel3.