Failure of the maternal uterine vascular system to adapt to pregnancy gives rise to serious complications such as gestational hypertension and preeclampsia. Relaxin (RLX) is a potent vasodilator and regulates maternal renal vascular adaptations in early pregnancy1. We hypothesised that a lack of RLX in pregnancy results in inadequate uterine vascular remodelling and contributes to vascular complications of pregnancy.
Aims: To examine passive mechanical wall properties of the uterine artery in pregnant RLX-deficient (Rln−/−) mice, and investigate the effects of relaxin (rhRLX) treatment on uterine artery remodelling.
Methods: Main uterine arteries were collected from pregnant Rln+/+ and Rln−/− mice aged 4 and 7 months (M) on day (D) 17.5 gestation and mounted on a pressure myograph. In a second study, uterine arteries were collected from 7M Rln+/+ and Rln−/− mice that received either vehicle or 3.33μg/h/kg rhRLX subcutaneously for 5 days via osmotic minipumps implanted on D12.5 gestation. Arteries were pressurised in 10mmHg steps and vessel dimensions recorded to construct stress-strain relationships to assess passive wall stiffness. ECM and adhesion molecule gene expression was by assessed PCR Arrays (SABiosciences).
Results: There was no effect of genotype on uterine artery compliance in 4M pregnant mice. However, 7M pregnant Rln−/− mice had significantly stiffer uterine arteries compared with Rln+/+ mice. This phenotype was rescued by treatment with rhRLX. There was no significant effect of RLX deficiency on vascular collagen expression. However, we identified novel ECM and adhesion molecules that were significantly affected in uterine arteries of Rln-/- pregnant mice, including Tgfβ1, Vtn, MMPs, and Eln. Furthermore, there was an up-regulation of Rxfp1 in the uterine arteries of young Rln−/− mice, which was absent in aged mice.
Summary: These data demonstrate that RLX deficiency during pregnancy may compromise uterine artery structure and function through inadequate vascular remodelling.