Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA.
Department of Obstetrics and Gynecology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792, USA.
Int J Mol Sci. 2020 Mar 18;21(6):2079. doi: 10.3390/ijms21062079.
During pregnancy, the uterine artery (UA) undergoes extensive remodeling to permit a 20-40 fold increase in blood flow with associated changes in the expression of a multitude of genes. This study used next-gen RNA sequencing technology to identify pathways and genes potentially involved in arterial adaptations in pregnant rat UA (gestation day 20) compared with non-pregnant rat UA (diestrus). A total of 2245 genes were differentially expressed, with 1257 up-regulated and 970 down-regulated in pregnant UA. Gene clustering analysis revealed a unique cluster of suppressed genes implicated in calcium signaling pathway and vascular smooth muscle contraction in pregnant UA. Transcription factor binding site motif scanning identified C2H2 ZF, AP-2 and CxxC as likely factors functional on the promoters of down-regulated genes involved in calcium signaling and vascular smooth muscle contraction. In addition, 1686 genes exhibited alternative splicing that were mainly implicated in microtubule organization and smooth muscle contraction. Cross-comparison analysis identified novel genes that were both differentially expressed and alternatively spliced; these were involved in leukocyte and B cell biology and lipid metabolism. In conclusion, this first comprehensive study provides a valuable resource for understanding the molecular mechanism underlying gestational uterine arterial adaptations during pregnancy.
在妊娠期间，子宫动脉 (UA) 经历广泛的重塑，以允许血液流量增加 20-40 倍，同时伴随大量基因表达的变化。本研究使用下一代 RNA 测序技术，比较了妊娠大鼠 UA（妊娠第 20 天）与非妊娠大鼠 UA（间情期）中可能参与动脉适应的途径和基因。共有 2245 个基因差异表达，妊娠 UA 中有 1257 个上调和 970 个下调。基因聚类分析显示，妊娠 UA 中存在一个独特的受抑制基因簇，涉及钙信号通路和血管平滑肌收缩。转录因子结合位点 motif 扫描确定 C2H2 ZF、AP-2 和 CxxC 可能是参与钙信号和血管平滑肌收缩的下调基因启动子上的功能因子。此外，1686 个基因表现出剪接体的选择性剪接，主要涉及微管组织和平滑肌收缩。交叉比较分析确定了既差异表达又选择性剪接的新基因；这些基因参与白细胞和 B 细胞生物学和脂质代谢。总之，这项首次全面研究为理解妊娠期间子宫动脉适应性的分子机制提供了有价值的资源。
