The Journal of Practical Medicine >
Study on the mechanism of PPARγ‐Targeted intervention in abnormal lipid Metabolism‐Induced dysfunction in placental trophoblast cells in preeclampsia and its clinical relevance
Received date: 2025-04-07
Online published: 2025-08-28
Objective To investigate the causal relationship between abnormal placental lipid metabolism and trophoblast dysfunction in patients with preeclampsia （PE）， and to explore the regulatory effects of PPARγ on trophoblast function under hypoxic conditions. Methods Placental tissues were collected from 30 patients with PE and 30 individuals with normal pregnancies at the General Hospital of Ningxia Medical University between October 2020 and November 2021 for the analysis of lipid deposition. A rat model of PE was established， comprising a sham-operated （Sham） group and a reduced uterine perfusion pressure （Rupp） group， with six rats in each group （n = 12 total）. Human trophoblast cells （HTR-8/SVneo） were cultured in vitro and randomly assigned to four experimental groups： normoxic control， hypoxia， hypoxia+PPARγ agonist （Rosiglitazone）， and hypoxia+PPARγ antagonist （T0070907）. The expression levels of lipid metabolism-related genes and transcription factors （FASN， FABP4， PPARγ， LXRα） were assessed using RT-qPCR. Western blotting was performed to determine the protein expression levels of PPARγ. Cell migration and invasion capacities were evaluated using scratch wound healing and Transwell assays， respectively. Results Placental lipid deposition in the PE group was significantly higher than that in the control group， particularly in the Rupp model mice （P < 0.001）. Under hypoxic conditions， the expression levels of FASN and FABP4 were upregulated in trophoblast cells （P < 0.001）， whereas the expression of PPARγ and LXRα was downregulated （P < 0.001）. Furthermore， treatment with the PPARγ antagonist T0070907 exacerbated the inhibitory effects of hypoxia on cell function （P < 0.001）， significantly reducing cell invasion and migration capacity （P < 0.001）. Additional siRNA-mediated knockdown experiments confirmed that PPARγ deficiency further aggravated hypoxia-induced impairments in cell migration and invasion， and this detrimental effect could not be reversed by Rosiglitazone. Conclusions Abnormal placental lipid metabolism in PE is closely linked to PPARγ-mediated enhancement of lipid synthesis and metabolic dysregulation under hypoxic conditions， which may subsequently impair trophoblast invasion and migration.
Jingrui LI , Yaoyu SUO , Tian TIAN , Ping CAO , Zhifeng DONG , Nan JIANG , Huiping ZHANG , Kai WU , Qing SHI , Guizhong. LI . Study on the mechanism of PPARγ‐Targeted intervention in abnormal lipid Metabolism‐Induced dysfunction in placental trophoblast cells in preeclampsia and its clinical relevance[J]. The Journal of Practical Medicine, 2025 , 41(16) : 2489 -2497 . DOI: 10.3969/j.issn.1006-5725.2025.16.008
| [1] | ALI M， AHMED M， MEMON M， et al. Preeclampsia： A comprehensive review［J］. Clin Chim Acta， 2024， 563（15）： 119922. doi:10.1016/j.cca.2024.119922 |
| [2] | 于素美， 张玉月， 马丽文， 等. MiR?15a?5p对子痫前期胎盘滋养细胞自噬的影响［J］. 实用医学杂志， 2024， 40（12）： 1631-1636. |
| [3] | ROBERTS J M. Preeclampsia epidemiology （ies） and pathophysiology （ies）［J］. Best Pract Res Clin Obstet Gynaecol， 2024，94： 102480. doi:10.1016/j.bpobgyn.2024.102480 |
| [4] | CHEN A， YU R， JIANG S， et al. Recent advances of microRNAs， long non-coding RNAs， and circular RNAs in preeclampsia［J］. Front Physiol， 2021， 12： 659638. doi:10.3389/fphys.2021.659638 |
| [5] | NEGRE-SALVAYRE A， SWIADER A， SALVAYRE R， et al. Oxidative stress， lipid peroxidation and premature placental senescence in preeclampsia［J］. Arch Biochem Biophys， 2022， 730： 109416. doi:10.1016/j.abb.2022.109416 |
| [6] | ZHAO Y， ZHAO G， LI W. MicroRNA-495 suppresses pre-eclampsia via activation of p53/PUMA axis［J］. Cell Death Discov， 2022， 8（1）： 132. doi:10.1038/s41420-022-00874-0 |
| [7] | 黄洁， 韩健， 郭建新， 等. 子痫前期发病机制研究新进展［J］. 解放军医学杂志， 2025，50（3）： 1-12. |
| [8] | MULDER J W， KUSTERS D M， VAN LENNEP J E R， et al. Lipid metabolism during pregnancy： Consequences for mother and child［J］. Curr Opin Lipidol， 2024， 35（3）： 133-140. doi:10.1097/mol.0000000000000927 |
| [9] | BOTTA M， AUDANO M， SAHEBKAR A， et al. PPAR agonists and metabolic syndrome： An established role？［J］. Int J Mol Sci， 2018， 19（4）： 1197. doi:10.3390/ijms19041197 |
| [10] | 黄文亭， 曾子纯， 王冬菊， 等. 改良减少子宫血流灌注法建立子痫前期大鼠模型［J］. 中国实验动物学报， 2019， 27（6）： 776-780. |
| [11] | ZHOU W， WANG H， YANG Y， et al. Trophoblast cell subtypes and dysfunction in the placenta of individuals with preeclampsia revealed by single-cell RNA sequencing［J］. Mol Cells， 2022， 45（5）： 317-328. doi:10.14348/molcells.2021.0211 |
| [12] | HE B， LIU Y， MAURYA M R， et al. The maternal blood lipidome is indicative of the pathogenesis of severe preeclampsia ［J］. Lipid Res， 2021， 62： 100118. doi:10.1016/j.jlr.2021.100118 |
| [13] | KHAIRE A A， THAKAR S R， WAGH G N， et al. Placental lipid metabolism in preeclampsia［J］. J Hypertens， 2021， 39（1）： 127-134. doi:10.1097/hjh.0000000000002596 |
| [14] | 吴允， 高颖， 王芳， 等. 糖脂代谢状况与子痫前期合并胎儿生长受限的相关性分析［J］. 贵州医药， 2025， 49（5）： 792-794. |
| [15] | HU M， LI J， BAKER P N， et al. Revisiting preeclampsia： A metabolic disorder of the placenta ［J］. FEBS J， 2022， 289（2）： 336-354. doi:10.1111/febs.15745 |
| [16] | WANG Y， SSENGONZI R， TOWNLEY-TILSON W D， et al. The Roles of Obesity and ASB4 in Preeclampsia Pathogenesis［J］. Int J Mol Sci， 2024， 25（16）： 9017. doi:10.3390/ijms25169017 |
| [17] | 肖燕璇， 张立力， 黎嘉琪， 等. 单胎子痫前期孕妇产前体质量指数与母婴结局关系探讨［J］. 实用医学杂志， 2023， 39（18）： 2357-2361. |
| [18] | DUTTA S， LAI A， SCHOLZ-ROMERO K， et al. Hypoxia-induced small extracellular vesicle proteins regulate proinflammatory cytokines and systemic blood pressure in pregnant rats［J］. Clin Sci， 2020， 134（6）： 593-607. doi:10.1042/cs20191155 |
| [19] | BAKRANIA B A， GEORGE E M， GRANGER J P. Animal models of preeclampsia： Investigating pathophysiology and therapeutic targets［J］. Am J Obstet Gynecol， 2022， 226（2）： S973-S987. doi:10.1016/j.ajog.2020.10.025 |
| [20] | GUERBY P， TASTA O， SWIADER A， et al. Role of oxidative stress in the dysfunction of the placental endothelial nitric oxide synthase in preeclampsia［J］. Redox Biol， 2021， 40： 101861. doi:10.1016/j.redox.2021.101861 |
| [21] | SCHWARTZ K S， SUN M， JALAL D I， et al. Reduced AT2R Signaling Contributes to Endothelial Dysfunction After Preeclampsia［J］. Hypertension， 2025， 82（5）： 904-913. doi:10.1161/hypertensionaha.124.24098 |
| [22] | LI Y， MA L， HE R， et al. Pregnancy Metabolic Adaptation and Changes in Placental Metabolism in Preeclampsia［J］. Geburtshilfe Frauenheilkd， 2024，84（11）：1033-1042. doi:10.1055/a-2403-4855 |
| [23] | MILLEN K R， BUHIMSCHI C， TABBAH S， et al. 741： Fatty acid synthase （FASN） expression in reproductive tissues and amniotic fluid free fatty acids （FFA） in pregnancies complicated by preeclampsia （PE）［J］. Am J Obstet Gynecol， 2015， 212（1）： S362. doi:10.1016/j.ajog.2014.10.947 |
| [24] | ZHANG Y， LIANG J， GU H， et al. Activation of LXRα attenuates 2-Ethylhexyl diphenyl phosphate （EHDPP） induced placental dysfunction［J］. Ecotoxicol Environ Saf， 2023， 266： 115605. doi:10.1016/j.ecoenv.2023.115605 |
| [25] | LEE J M， HAMMARéN H M， SAVITSKI M M， et al. Control of protein stability by post-translational modifications［J］. Nat Commun， 2023， 14（1）： 201. doi:10.1038/s41467-023-35795-8 |
| [26] | NIKOLSKY K S， KULIKOVA L I， PETROVSKIY D V， et al. Analysis of structural changes in the protein near the phosphorylation site［J］. Biomolecules， 2023， 13（11）： 1564. doi:10.3390/biom13111564 |
| [27] | BRUNMEIR R， XU F. Functional regulation of PPARs through post-translational modifications［J］. Int J Mol Sci， 2018， 19（6）： 1738. doi:10.3390/ijms19061738 |
| [28] | YANG N， WANG Y， TIAN Q， et al. Blockage of PPARγ T166 phosphorylation enhances the inducibility of beige adipocytes and improves metabolic dysfunctions［J］. Cell Death Differ， 2023， 30（3）： 766-778. doi:10.1038/s41418-022-01077-x |
| [29] | ZHOU J， JIANG S， LIU D， et al. Bidirectional Mendelian Randomization Analysis of Genetic Proxies of Plasma Fatty Acids and Pre-Eclampsia Risk［J］. Nutrients， 2024， 16（21）： 3748. doi:10.3390/nu16213748 |
| [30] | HUDA S S， FORREST R， PATERSON N， et al. In preeclampsia， maternal third trimester subcutaneous adipocyte lipolysis is more resistant to suppression by insulin than in healthy pregnancy［J］. Hypertension， 2014， 63（5）： 1094-1101. doi:10.1161/hypertensionaha.113.01824 |
| [31] | ABDELZAHER W Y， MOSTAFA-HEDEAB G， BAHAA H A， et al. Leukotriene receptor antagonist， montelukast ameliorates L-Name-induced pre-eclampsia in rats through suppressing the IL-6/Jak2/STAT3 signaling pathway［J］. Pharmaceuticals， 2022， 15（8）： 914. doi:10.3390/ph15080914 |
| [32] | 刘静， 朱文秀， 孟金来， 等. 胎盘植入性疾病发病机制的研究进展［J］. 现代妇产科进展， 2025， 34（02）： 147-149+154. |
| [33] | LAI W， YU L， DENG Y. PPARγ alleviates preeclampsia development by regulating lipid metabolism and ferroptosis［J］. Commun Biol， 2024， 7（1）： 429. doi:10.1038/s42003-024-06063-2 |
/
| 〈 |
|
〉 |