MPS 13-06 APPLICATION OF NOVEL REDUCED UTERINE PERFUSION PRESSURE (RUPP) MODEL OF PREECLAMPSIA IN C57BL/6J 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. We established novel RUPP model of PE in outbred ICR-strain. The aim of the present study is to develop RUPP model ofC57BL/6J (B6)-strain mice, widely used strain in genetically engineered mice. Design and Method: We bilaterally ligated ovarian vessels distal to ovarian branches, uterine vessels, or both in B6-strain mice at 14.5 days post coitum (dpc). BP, renal phenotype and pregnancy outcome were analyzed. Results: Unlike the RUPP models in ICR-strain mice, ligation of ovarian vessels distal to ovarian branches, uterine vessels without space caused miscarriage in B6-strain mice. We next tied uterine vessels with nylon thread, followed by removal of the thread to provide a small space. This caused significant fetal growth restriction. Conclusions: Pregnancy outcome caused by RUPP in mice was different depending on mouse strains. This model is expected to be useful for investigating pathogenesis of PE in genetically engineered mice and for evaluating new therapies for PE.