The BPH/5 Mouse Model of Superimposed Preeclampsia Is Not a Model of HELLP Syndrome

Abstract

Preeclampsia (PE) is a multisystemic disease of pregnancy affecting 2–8% of women worldwide. PE-induced liver disease is a rare but important complication of pregnancy. The pathogenesis of liver dysfunction in PE is poorly understood, but is correlated with dysregulated angiogenic, inflammatory, and hypoxic events in the early phase of placental development. Because BPH/5 mice develop the maternal and fetal hallmarks of PE during pregnancy, we hypothesized that they may also share the clinicopathologic findings of the human PE-associated hemolysis elevated liver transaminases low platelets (HELLP) syndrome. Using this model, we determined that microangiopathic hemolysis, thrombocytopenia, and elevated liver enzymes do not occur in mid to late gestation. Pregnant BPH/5 mice do not develop histologic evidence of hepatic inflammation, but they do have increased microsteatosis scores at preconception and in mid to late gestation that progress to macrosteatosis in a subset of mice in late gestation. The transcriptional upregulation of TNF-α, CXCL-10, and TLR-2 occurs in mid gestation prior to the onset of macrosteatosis. The BPH/5 female mouse is not a model of HELLP syndrome, but may be a model of fatty liver disease associated with pregnancy.

Mouse models of preeclampsia with preexisting comorbidities

“…Disruption of normal placental development and smaller fetal weight at birth suggests that this model may be similar to early-onset preeclampsia with fetal growth restriction ( Waker et al, 2021 ). Recent studies; however, have changed the context of the BPH/5 model and expanded the comorbidity beyond spontaneous chronic borderline hypertension and to now include preexisting metabolic disease, obesity, and fatty liver disease ( Sutton et al, 2017 ; Reijnders et al, 2019 ; Johnston et al, 2021 ; Sones et al, 2021 ).…”

Pathophysiological impact of CXC and CX3CL1 chemokines in preeclampsia and gestational diabetes mellitus

“…Likewise, references indicated that CXCL2 is upregulated in PE patients and the blood pressure high/5 (BPH/5) female mouse model of PE ( Yan et al, 2013 ; Batts et al, 2021 ). Interestingly, Johnston and others ( Johnston et al, 2021 ) observed that CXCL2 mRNA expression was considerably lower in PE hepatic transaminases low platelets (HELLP) mouse model syndrome. The decreasing trend of CXCL2 during late pregnancy is unknown.…”

Animal Models of Cardiovascular Complications of Pregnancy

“…However, BPH/5 mice do not develop features of severe disease, such as HELLP syndrome. 69 Many groups have attempted to study the mechanisms of why this strain develops preeclampsia-like states. Sones et al 70 have suggested that antiangiogenic sFLT1 protein was upregulated in the BPH/5 placentas and that aberrant sFLT1 expression was responsible for the complement activation and poor placentation in this model.…”