67 Application of a novel RUPP model to C57BL/6J mice

Abstract

Introduction Reduction of uterine blood flow is useful for studying pathogenesis of preeclampsia (PE). Although reduced uterine perfusion pressure (RUPP) is widely used as a model of PE in rats, investigating the genetics of PE has been slow because it has been difficult to make a useful RUPP model in mice. Moreover, rat model of RUPP does not allow one to measure BP using tail cuffs. We established a novel RUPP model of PE in outbred ICR mice, which allows one to evaluate BP using tail cuff (Fushima et al. PLOS ONE, 2016). Objectives The aim of the present study is to develop RUPP model of C57BL/6J (B6) mice, a widely used strain in genetically engineered mice. Methods We bilaterally ligated ovarian vessels distal to ovarian branches, uterine vessels, or both in B6 mice at 14.5 dpc. BP, renal phenotype and pregnancy outcome were analyzed. Results Unlike the RUPP model in ICR mice, ligation of ovarian vessels or uterine vessels caused miscarriages in B6 mice. We next tied uterine vessels with a nylon thread, followed by removal of the thread to provide a small space for a little blood flow. This caused significant fetal growth restriction. Different from ICR mice BP changes were insignificant. Conclusions Pregnancy outcome caused by RUPP is different depending on the strains of mice. This RUPP model is expected to be useful for investigating pathogenesis of PE and FGR in genetically engineered mice and for evaluating new therapies for these conditions.