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.

中文翻译：

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易中风自发性高血压大鼠妊娠早期不同的子宫动脉基因表达谱

在怀孕期间，子宫螺旋动脉经历了主要的血管重塑，以确保有足够的子宫胎盘灌注来支持胎儿。在合并高血压疾病的妊娠中，这种重塑不足会导致子宫胎盘血流受损以及母婴结局不佳。血管重塑失败的潜在遗传机制尚不完全清楚。本研究旨在检查与正常血压大鼠 Wistar-Kyoto 大鼠 (WKY) 相比，易中风自发性高血压大鼠 (SHRSP) 子宫动脉中早期妊娠相关基因的变化。来自妊娠第 6.5 天 WKY 和 SHRSP 的子宫动脉被处理用于 RNA 测序，以及每种菌株的原始、年龄匹配的对照。^®）。这项研究发现，来自早期妊娠的 WKY 子宫动脉表现出一种基因表达模式，表明妊娠依赖性 Ca ²⁺处理和 RAAS 成分减少以及 ATP 产生增加。相比之下，妊娠 SHRSP 子宫动脉的表达模式主要由免疫反应升高和 ROS 和 RAAS 下游效应物的产生增加主导。这些结果表明，在大鼠模型中，妊娠期高血压早在妊娠第一周就会影响子宫动脉基因表达模式。所涉及的通路变化可能是或促成在妊娠晚期 SHRSP 中观察到的不良血管重塑和由此产生的胎盘缺血和全身血管功能障碍。