Hepatic steatosis precedes pregnancy in the BPH/5 preeclampsia‐like mouse model

Abstract

BPH/5 mice represent a superimposed model of preeclampsia that spontaneously develop maternal and fetal characteristics of preeclamptic pregnancies. In women, the development of preeclampsia is associated with pre-existing dysregulation of lipid metabolism including hepatic steatosis. The study objective was tocharacterize the basal hepatic health of the female BPH/5 mouse to determine if hepatic steatosis precedes the preeclampsia-like syndrome. We hypothesized that non-pregnant female BPH/5 mice have an excess of hepatocellular lipid that promotes intrahepatic pro-inflammatory cytokine production. Blood and liver samples were collected from 8–10-week-old BPH/5 non-pregnant females (n=10) and 8–10-week-old C57Bl/6 non-pregnant females (n=6). Liver and body weight were recorded. Biochemical markers of hepatocellular function (albumin, ALT, BUN, and bilirubin) were quantified. Hepatic RNA was isolated, and qPCR was used to evaluate pro-inflammatory markers. H&E staining was used to evaluate hepatic histomorphology and lipid accumulation. There was no significant difference in albumin, ALT, BUN, or bilirubin between BPH/5 and C57Bl/6 mice. There was significantly higher hepatic CXCL-2, CXCL-10, IL-1ß, TLR2, and TLR7 mRNA expression in BPH/5 versus C57Bl/6 mice (p<0.05). There was a significantly greater liver weight in BPH/5 mice compared to C57Bl/6 mice (p=0.05). The histologic microsteatosis score was significantly increased in the BPH/5 mice (2.5) compared to C57Bl/6 mice (0.98, p=0.025). The BPH/5 mouse has basal hepatic steatosis and a pro-inflammatory hepatic phenotype that precedes pregnancy. Dysregulated lipid metabolism in the liver may contribute to the development of preeclampsia.