Hung Shao-Chi, Chan Te-Fu, Chan Hsiu-Chuan, Wu Chia-Ying, Chan Mei-Lin, Jhuang Jie-Yang, Tan Ji-Qin, Mei Jia-Bin, Law Shi-Hui, Ponnusamy Vinoth Kumar, Chan Hua-Chen, Ke Liang-Yin
Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 807378, Taiwan.
Graduate Institute of Medicine, College of Medicine & Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807378, Taiwan.
Antioxidants (Basel). 2024 Aug 19;13(8):1007. doi: 10.3390/antiox13081007.
Gestational diabetes mellitus (GDM) is a common pregnancy disorder associated with an increased risk of pre-eclampsia and macrosomia. Recent research has shown that the buildup of excess lipids within the placental trophoblast impairs mitochondrial function. However, the exact lipids that impact the placental trophoblast and the underlying mechanism remain unclear. GDM cases and healthy controls were recruited at Kaohsiung Medical University Hospital. The placenta and cord blood were taken during birth. Confocal and electron microscopy were utilized to examine the morphology of the placenta and mitochondria. We determined the lipid composition using liquid chromatography-mass spectrometry in data-independent analysis mode (LC/MS). In vitro studies were carried out on choriocarcinoma cells (JEG3) to investigate the mechanism of trophoblast mitochondrial dysfunction. Results showed that the GDM placenta was distinguished by increased syncytial knots, chorangiosis, lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) overexpression, and mitochondrial dysfunction. Lysophosphatidylcholine (LPC) 16:0 was significantly elevated in the cord blood LDL of GDM patients. In vitro, we demonstrated that LPC dose-dependently disrupts mitochondrial function by increasing reactive oxygen species (ROS) levels and HIF-1α signaling. In conclusion, highly elevated LPC in cord blood plays a pivotal role in GDM, contributing to trophoblast impairment and pregnancy complications.
妊娠期糖尿病（GDM）是一种常见的妊娠疾病，与子痫前期和巨大儿风险增加有关。最近的研究表明，胎盘滋养层细胞内过量脂质的积累会损害线粒体功能。然而，影响胎盘滋养层细胞的确切脂质及其潜在机制仍不清楚。在高雄医学大学医院招募了GDM病例和健康对照。在分娩时采集胎盘和脐带血。利用共聚焦显微镜和电子显微镜检查胎盘和线粒体的形态。我们采用液相色谱-质谱联用的数据非依赖分析模式（LC/MS）测定脂质组成。对绒毛膜癌细胞（JEG3）进行体外研究，以探讨滋养层细胞线粒体功能障碍的机制。结果显示，GDM胎盘的特征是合体结节增加、绒毛膜血管增多、凝集素样氧化低密度脂蛋白（LDL）受体-1（LOX-1）过表达以及线粒体功能障碍。GDM患者脐带血低密度脂蛋白中的溶血磷脂酰胆碱（LPC）16:0显著升高。在体外，我们证明LPC通过增加活性氧（ROS）水平和缺氧诱导因子-1α（HIF-1α）信号传导，以剂量依赖的方式破坏线粒体功能。总之，脐带血中高度升高的LPC在GDM中起关键作用，导致滋养层细胞损伤和妊娠并发症。
