Evidence of proteinuria, but no other characteristics of pre-eclampsia, in relaxin-deficient mice

Abstract

Pre-eclampsia (PE) is a leading cause of maternal and fetal death, characterised by an imbalance of placental growth factors and hypertension at >20 weeks gestation. Impaired maternal systemic vascular adaptations and fetal growth restriction are features of both PE and pregnant relaxin-deficient (Rln–/–) mice. The aim of the present study was to investigate whether these phenotypes in Rln–/– mice are associated with abnormal placental growth factor expression, increased soluble fms-like tyrosine kinase-1 (sFlt-1), proteinuria and/or hypertension during pregnancy. In addition, we examined relaxin and relaxin receptor (relaxin/insulin like family peptide receptor 1 (RXFP1)) mRNA expression in placentas of women with PE. There was no significant difference in placental vascular endothelial growth factor A (VegfA) and placenta growth factor (Plgf) gene expression between Rln–/– and wild-type mice. Circulating plasma sFlt-1 concentrations in pregnant mice of both genotypes and ages were increased compared with non-pregnant mice but were lower in younger pregnant Rln–/– mice compared with aged-matched Rln+/+ mice. Aged pregnant Rln–/– mice had higher urinary albumin : creatinine ratios compared with age-matched Rln+/+ mice, indicative of proteinuria. Systolic and diastolic blood pressures did not differ between genotypes. In addition, PE in women was not associated with altered placental mRNA expression of RLN2 or RXFP1 at term. Overall, the data demonstrate that pregnant Rln–/– mice do not have the typical characteristics of PE. However, these mice show evidence of proteinuria, but we suggest that this results from systemic renal vascular dysfunction before pregnancy.