Whole-Genome Uterine Artery Transcriptome Profiling and Alternative Splicing Analysis in Rat Pregnancy

Abstract

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.