OS 21-08 NOVEL REDUCED UTERINE PERFUSION PRESSURE (RUPP) MODEL OF PREECLAMPSIA IN MICE

Abstract

Objective: Preeclampsia (PE) is a pregnancy-induced hypertension with proteinuria that typically develops after 20 weeks of gestation. A reduction in uterine blood flow causes placental ischemia and placental release of anti-angiogenic factors such as soluble fms-like tyrosine kinase (sFlt-1) followed by PE. Although the reduced uterine perfusion pressure (RUPP) model is widely used in rats, investigating the genetics of PE has been problematic because it has been difficult to make a useful RUPP model in mice. The aim of the present study is to establish a novel PE model using an improved RUPP method in mice. Design and Method: As shown in the Figure 1B, we bilaterally ligated ovarian vessels distal to ovarian branches, uterine vessels, or both in ICR-strain mice at 14.5 days post coitum (dpc). BP, renal phenotype and pregnancy outcome were analyzed. Results: Unlike the RUPP models described in the literature, this model did not constrict the abdominal aorta, which allowed BP to be measured with a tail cuff. RUPP in mice had elevated BP, increased urinary albumin excretion, severe endotheliosis, and mesangial expansion. They also had an increased incidence of miscarriage and premature delivery. Embryonic weight at 18.5 dpc was significantly lower than that in sham mice. The closer to the ligation site the embryos were, the higher the resorption rate and the lower the embryonic weight. The phenotype was more severe in the order of ligation at the ovarian vessels < uterine vessels < both. Conclusions: We developed a novel RUPP mouse model that recapitulates the phenotype of PE. This model is expected to be useful for investigating pathogenesis of PE in genetically engineered mice and for evaluating new therapies for PE.