Characterisation of the Selective Reduced Uteroplacental Perfusion (sRUPP) Model of Preeclampsia

Abstract

Preeclampsia is a complication of pregnancy characterised by gestational hypertension, proteinuria and/or end organ disease. The reduced uteroplacental perfusion (RUPP) model, via partial occlusion of the lower abdominal aorta, mimics insufficient placental perfusion as a primary causal characteristic of preeclampsia. However, a major limitation of the RUPP model is that perfusion is reduced to the entire hindquarters of the rat resulting in hindlimb ischemia. We hypothesised that clipping the uterine and ovarian arteries in the selective (s)RUPP model would provoke signs of preeclampsia while avoiding systemic ischemia. Sham, RUPP or sRUPP procedures were performed in pregnant Sprague Dawley rats on gestational day (GD)14. On GD21 uterine blood flow was significantly reduced in both the RUPP and sRUPP models while aortic flow was reduced only in RUPP. Both models resulted in increased MAP, increased vascular oxidative stress (superoxide generation), increased pro-inflammatory (RANTES) and reduced pro-angiogenic (endoglin) mediators. Vascular compliance and constriction were unaltered in either RUPP or sRUPP groups. In summary, refinements to the RUPP model simultaneously maintain the characteristic phenotype of preeclampsia and avoid peripheral ischemia; providing a useful tool which may be used to increase our knowledge and bring us closer to a solution for women affected by preeclampsia.

Role of B1 and B2 lymphocytes in placental ischemia-induced hypertension

“…A most recent study by Morgan et al (57) used telemetry to continuously monitor mean arterial pressure from GD7-21 in the rat RUPP model and reports an approximate 10-mmHg increase that peaks at GD17.5-18.5. Reported MAP in sham surgical controls or normal pregnant animals ranges from 92 to 108 mmHg, whereas RUPP MAP ranges from 101 to 137 mmHg (5,26,31,38,57). The statistically significant increase in MAP in our study, coupled with the decreased fetal and placental weight, indicate the validity of the RUPP procedure.…”

Hydrogen sulfide releasing molecule MZe786 inhibits soluble Flt-1 and prevents preeclampsia in a refined RUPP mouse model

“…Attempts to improve the model by restricting the blood flow specifically to the uteroplacental units in rats resulted in increased blood pressure. However, many of the prominent features of preeclampsia including elevated sFlt-1 levels and renal damage were absent [ 35 , 36 ]. An earlier report of RUPP in C57Bl/6 J mice used restriction of abdominal aorta and ovarian arteries making the preeclamptic symptoms unspecific to uteroplacental perfusion [ 18 ].…”

Acid Sensing Ion Channel 2a Is Reduced in the Reduced Uterine Perfusion Pressure Mouse Model and Increases Seizure Susceptibility in Pregnant Mice

“…The current study used a version of the RUPP described by Fushima et al where the authors reported several characteristics similar to the preeclampsia patient and the rat RUPP model [ 19 ]. While the majority of studies utilizing RUPP surgery are performed in rats [ 22 , 23 , 24 , 25 ], the use of a mouse RUPP model allows investigators to directly test the involvement of specific pathways by using genetic mouse models. Hallmarks of the rat RUPP model mimic features of clinical preeclampsia and include increased blood pressure; increased fetal demise; and an imbalance of maternal angiogenic factors PlGF, VEGF, and sFlt1 [ 26 , 27 , 28 , 29 ].…”