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
  • 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: [email protected].
  • 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: [email protected].
  • 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: [email protected].
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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