Whole-Genome Transcriptome Profiling in PFOS-treated Uterine Artery Endothelial Cells Isolated from Pregnant Women

Author(s): Jay S. Mishra and Sathish Kumar

Empirical evidence from human studies has demonstrated a correlative relationship between perfluorooctane sulfonate (PFOS) exposure and increased risks of preeclampsia and fetal developmental complications. Although experimental and circumstantial data suggest that PFOS induces endothelial dysfunction, leading to decreased uterine arterial blood flow and gestational hypertension, the precise regulatory mechanisms responsible for this effect remain unknown. To address this issue, we treated human uterine artery endothelial cells (hUAECs) isolated from pregnant women with 10 μmol/L PFOS or vehicle and conducted comparative transcriptomic analyses. We identified a total of 19 differentially expressed genes, 9 of which were upregulated and 10 were down-regulated in PFOS-treated pregnant hUAECs. Pre-ranked gene set enrichment analysis unveiled a distinct set of activated genes involved in osmotic stress, cellular stress response, translation regulation, metabolic regulation, and oxidationreduction processes in PFOS-treated pregnant hUAECs. Furthermore, PFOS treatment resulted in the down-regulation of genes implicated in cardiac muscle cell proliferation, embryonic morphogenesis, and muscle cell proliferation. In addition, we observed differential splicing events in 2678 genes in hUAECs exposed to PFOS, with cross-comparison analysis revealing 4 genes that were both differentially expressed and alternatively spliced and were implicated in oxidative stress and cardiac development. In conclusion, this study provides a comprehensive understanding of the molecular mechanisms underlying PFOS-induced gestational uterine artery endothelial dysfunction during pregnancy, offering a valuable resource for future research in this field.