2. Academic Validation
  3. M2 macrophage derived exosomal miR-20a-5p ameliorates trophoblast pyroptosis and placental injuries in obstetric antiphospholipid syndrome via the TXNIP/NLRP3 axis

M2 macrophage derived exosomal miR-20a-5p ameliorates trophoblast pyroptosis and placental injuries in obstetric antiphospholipid syndrome via the TXNIP/NLRP3 axis

  • Life Sci. 2025 Jun 1:370:123561. doi: 10.1016/j.lfs.2025.123561.
Hongyuan Zhang 1,  Ning Jiang 2,  Mingyang Xu 3,  Die Jing 2,  Tingting Dong 3,  Qian Liu 4,  Qingfeng Lv 5,  Ruiheng Huo 2,  Pengzheng Chen 6,  Lei Li 7,  Xietong Wang 8
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan 250021, Shandong, China; Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China; The Laboratory of Medical Science and Technology Innovation Center (Institute of Translational Medicine), Shandong First Medical University (Shandong Academy of Medical Sciences) of China, Jinan 250117, Shandong, China.
  • 2 Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China.
  • 3 Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan 250021, Shandong, China; Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China.
  • 4 Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan 250021, Shandong, China; Department of Obstetrics and Gynecology, Feixian County People's Hospital, Linyi 273400, Shandong, China.
  • 5 The Affiliated Taian City Central Hospital of Qingdao University, Taian 271000, Shandong, China.
  • 6 Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China. Electronic address: 18366118605@163.com.
  • 7 Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan 250021, Shandong, China; Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China; The Laboratory of Medical Science and Technology Innovation Center (Institute of Translational Medicine), Shandong First Medical University (Shandong Academy of Medical Sciences) of China, Jinan 250117, Shandong, China. Electronic address: lilei@sdfmu.edu.cn.
  • 8 Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan 250021, Shandong, China; Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China; The Laboratory of Medical Science and Technology Innovation Center (Institute of Translational Medicine), Shandong First Medical University (Shandong Academy of Medical Sciences) of China, Jinan 250117, Shandong, China. Electronic address: wxt65@sdfmu.edu.cn.
PMID: 40127859 DOI: 10.1016/j.lfs.2025.123561
Abstract

Aim: Obstetric antiphospholipid syndrome (OAPS) is a pregnancy-related complication characterized by trophoblast Pyroptosis and placental injury induced by antiphospholipid antibodies (aPLs). M2-polarized macrophage-derived exosomes (M2-exos) exert anti-inflammatory, immunomodulatory, and growth-promoting effects in various autoimmune diseases and tumors. However, their role in OAPS is not yet clear. Therefore, in this study, we isolated M2-exos from M2 macrophages and investigated their effects on trophoblast proliferation, death, migration, invasion, and Pyroptosis following stimulation using aPLs.

Main methods: First, we established an animal model of OAPS and thereafter treated the OAPS mice with exogenous M2-exos via injection through the tail vein. Then to clarify the roles of miR-20a-5p and thioredoxin-interacting protein (TXNIP) in OAPS, we performed gain- or loss-of-function assays, and used GraphPad Prism software to analyze the collected data with statistical significance set at P < 0.05.

Key findings: MicroRNAs (miRNAs) Sequencing revealed the enrichment of miR-20a-5p in M2-exos, and these M2-exos significantly alleviated aPLs-induced trophoblast dysfunction. Our results also indicated that M2-exos delivered miR-20a-5p to trophoblast cells directly targeted thioredoxin-interacting protein (TXNIP), and thus suppressed the TXNIP/NLRP3 pathway, reduced Pyroptosis and inflammation in trophoblast cells, and improved placental function and fetal development.

Significance: M2-exos improve pregnancy outcomes in OAPS via the miR-20a-5p/TXNIP/NLRP3 axis, and thus represent as a novel therapeutic approach for aPLs-induced OAPS.

Keywords

Exosome; M2-polarized macrophage; Obstetric antiphospholipid syndrome; Pyroptosis; TXNIP; miR-20a-5p.

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