title: Reduced Uterine Perfusion Pressure (RUPP) Model of Preeclampsia in Mice.
abstract: 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 sFlt-1 followed by PE. Although the reduced uterine perfusion pressure (RUPP) model is widely used in rats, investigating the role of genes on PE using genetically engineered animals has been problematic because it has been difficult to make a useful RUPP model in mice. To establish a RUPP model of PE in mice, we bilaterally ligated ovarian vessels distal to ovarian branches, uterine vessels, or both in ICR-strain mice at 14.5 days post coitum (dpc). Consequently, these 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. 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. This novel RUPP model in mice should be useful for investigating the pathogenesis of PE in genetically engineered mice and for evaluating new therapies for PE.
authors.affiliation: Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences and Faculty of Pharmaceutical Sciences, Sendai, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Fushima
authors.affiliation: Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences and Faculty of Pharmaceutical Sciences, Sendai, Japan.
authors.forename: Akiyo
authors.initials: A
authors.lastname: Sekimoto
authors.affiliation: Advanced Interdisciplinary Biomedical Engineering, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Minato
authors.affiliation: Advanced Interdisciplinary Biomedical Engineering, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Ito
authors.affiliation: Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Oe
authors.affiliation: Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Kisu
authors.affiliation: Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences and Faculty of Pharmaceutical Sciences, Sendai, Japan.|Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Sato
authors.affiliation: Japan Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai, Japan.|Institute of Fluid Science, Tohoku University, Sendai, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Funamoto
authors.affiliation: Institute of Fluid Science, Tohoku University, Sendai, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hayase
authors.affiliation: Advanced Interdisciplinary Biomedical Engineering, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Sadayoshi
authors.initials: S
authors.lastname: Ito
authors.affiliation: Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences and Faculty of Pharmaceutical Sciences, Sendai, Japan.|Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.affiliation: Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences and Faculty of Pharmaceutical Sciences, Sendai, Japan.|Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D015415:Biomarkers; D001794:Blood Pressure; D004195:Disease Models, Animal; D005260:Female; D046110:Hypertension, Pregnancy-Induced; D008026:Ligation; D008297:Male; D051379:Mice; D010477:Perfusion; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011507:Proteinuria; D012039:Regional Blood Flow; D018615:Ultrasonography, Doppler, Color; D014599:Uterus / Q000098:blood supply* / Q000000981:diagnostic imaging
chemical_list: D015415:Biomarkers