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

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.