Distinct uterine artery gene expression profiles during early gestation in the stroke-prone spontaneously hypertensive rat

Abstract

During pregnancy the uterine spiral arteries undergo major vascular remodelling to ensure sufficient uteroplacental perfusion to support the fetus. In pregnancies complicated by hypertensive disorders this remodelling is deficient leading to impaired uteroplacental blood flow and poor maternal and fetal outcomes. The underlying genetic mechanisms for failed vascular remodelling are not fully understood. This study aimed to examine the early-pregnancy associated gene changes in the uterine arteries of stroke-prone spontaneously hypertensive rats (SHRSP) compared to their normotensive counterparts, Wistar-Kyoto rats (WKY). Uterine arteries from gestational day 6.5 WKY and SHRSP were processed for RNA-sequencing, along with virgin, age-matched controls for each strain. Gene expression changes were identified and biological pathways were implicated and interpretated using Ingenuity Pathway Analysis (IPA®). This study found that WKY uterine arteries from early-pregnancy exhibit a gene expression pattern that is suggestive of a pregnancy-dependent reduction in Ca2+ handling and RAAS components and an increase in ATP production. In contrast, the expression pattern of pregnant SHRSP uterine arteries was dominated by an elevated immune response and increased production of ROS and downstream effectors of the RAAS. These results suggest that in a rat model, hypertension during pregnancy impacts uterine artery gene expression patterns as early as the first week of pregnancy. The pathway changes involved may underlie or contribute to the adverse vascular remodelling and resultant placental ischaemia and systemic vascular dysfunction observed in SHRSP in late gestation.

Preexisting hypertension and pregnancy-induced hypertension reveal molecular differences in placental proteome in rodents

“…We are confident that our analysis is valid as we were able to demonstrate differential regulation of some of the key pathogenetic principles including RAAS activation and oxidative stress in these models. In line with our proteomic data, Scott et al, through transcriptomics of uterine arteries show an elevated immune response, and increased production of reactive oxygen species and downstream effectors of the RAAS in pregnant SHRSP (38).…”

Multiomics Studies Investigating Recurrent Pregnancy Loss: An Effective Tool for Mechanism Exploration

“…A recent study applying RNA sequencing of spontaneously hypertensive stroke-prone rats (SHRSP) found that the gene expression pattern of pregnant SHRSP uterine arteries was dominated by increased reactive oxygen species and downstream effectors of the renin-angiotensin-aldosterone system. The disrupted pathway involved may contribute to adverse vascular remodeling and the resultant placental ischemia and systemic vascular dysfunction ( 39 ). Uterine spiral artery remodeling is essential for promoting blood flow to the placenta and fetal development, and omics could help us better understand this process.…”