Zhang Hongya, Li Huihui, Yao Jiatong, Zhao Miaomiao, Zhang Cong
Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, China.
Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China.
iScience. 2024 Jan 31;27(2):108899. doi: 10.1016/j.isci.2024.108899. eCollection 2024 Feb 16.
Preeclampsia (PE) is a pregnancy-specific hypertensive disorder that severely impairs maternal and fetal health. However, its pathogenesis remains elusive. NOP2/Sun5 (NSUN5) is an RNA methyltransferase. This study discovered a significant correlation between rs77133388 of and PE in a cohort of 868 severe PE patients and 982 healthy controls. To further explore this association, the researchers generated single-base mutant mice (NSUN5 R295C) at rs77133388. The pregnant NSUN5 R295C mice exhibited PE symptoms. Additionally, compared to the controls, the decidual area of the placenta was significantly reduced in NSUN5 R295C mice, and their decidualization was impaired with a significantly decrease in polyploid cell numbers after artificially induced decidualization. The study also found a decrease in phosphorylated JAK2, STAT3, and IL-11Rα, Cyclin D3 expression in NSUN5 R295C mice. Overall, these findings suggest that NSUN5 mutation potentially alters decidualization through the IL-11Rα/JAK2/STAT3/Cyclin D3 pathway, ultimately impairing placental development and contributing to PE occurrence.
子痫前期（PE）是一种妊娠期特有的高血压疾病，严重损害母婴健康。然而，其发病机制仍不清楚。NOP2/Sun5（NSUN5）是一种RNA甲基转移酶。本研究在868例重度子痫前期患者和982例健康对照组成的队列中发现了rs77133388与子痫前期之间存在显著相关性。为了进一步探究这种关联，研究人员构建了rs77133388位点的单碱基突变小鼠（NSUN5 R295C）。怀孕的NSUN5 R295C小鼠表现出子痫前期症状。此外，与对照组相比，NSUN5 R295C小鼠胎盘的蜕膜面积显著减小，人工诱导蜕膜化后其蜕膜化受损，多倍体细胞数量显著减少。该研究还发现NSUN5 R295C小鼠中磷酸化的JAK2、STAT3和IL-11Rα以及细胞周期蛋白D3的表达降低。总体而言，这些发现表明NSUN5突变可能通过IL-11Rα/JAK2/STAT3/细胞周期蛋白D3途径改变蜕膜化，最终损害胎盘发育并导致子痫前期的发生。
