Mishra Jay S, Kumar Sathish
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, United States of America.
Department of Obstetrics and Gynecology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, United States of America.
J Environ Sci Public Health. 2023;7(2):79-93. doi: 10.26502/jesph.96120189. Epub 2023 May 24.
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 oxidation-reduction processes in PFOS-treated pregnant hUAECs. Furthermore, PFOS treatment resulted in the downregulation 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.
来自人体研究的经验证据表明，全氟辛烷磺酸（PFOS）暴露与子痫前期风险增加和胎儿发育并发症之间存在关联关系。尽管实验数据和间接证据表明，PFOS会导致内皮功能障碍，进而导致子宫动脉血流减少和妊娠期高血压，但造成这种影响的确切调控机制仍不清楚。为了解决这个问题，我们用10 μmol/L PFOS或溶剂处理从孕妇中分离出的人子宫动脉内皮细胞（hUAECs），并进行了比较转录组分析。我们总共鉴定出19个差异表达基因，其中9个在PFOS处理的妊娠hUAECs中上调，10个下调。预排名基因集富集分析揭示了一组在PFOS处理的妊娠hUAECs中参与渗透应激、细胞应激反应、翻译调控、代谢调控和氧化还原过程的不同激活基因。此外，PFOS处理导致参与心肌细胞增殖、胚胎形态发生和肌肉细胞增殖的基因下调。此外，我们在暴露于PFOS的hUAECs中的2678个基因中观察到差异剪接事件，交叉比较分析揭示了4个基因既差异表达又可变剪接，且与氧化应激和心脏发育有关。总之，本研究全面了解了PFOS诱导孕期妊娠子宫动脉内皮功能障碍的分子机制，为该领域的未来研究提供了宝贵资源。
