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Updated: Jul 22, 2026

Isolation of Leukocytes from the Human Maternal-fetal Interface
08:19

Isolation of Leukocytes from the Human Maternal-fetal Interface

Published on: May 21, 2015

16.6K

Reciprocal activation between M1 macrophages and trophoblasts through CXCL9/STAT1/ZEB1/CCL2 axis promotes recurrent

Sisi Yan1, Xiang Wang1, Qiuji Wu1

  • 1Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.

Frontiers in Immunology
|November 24, 2025
PubMed
Abstract

Insights

M1 macrophages inhibit trophoblast function in recurrent spontaneous abortion (RSA) by releasing CXCL9, a key factor in this immune-related pregnancy complication. This interaction highlights a novel pathway impacting early pregnancy health.

Area of Science:

  • Immunology
  • Reproductive Biology
  • Cell Biology

Background:

  • Crosstalk between macrophages and trophoblasts is critical in recurrent spontaneous abortion (RSA).
  • M1 macrophages (M1-Mφ) are found in RSA decidual tissues, but their specific effects on trophoblasts are unclear.
  • Understanding this interaction is key to addressing RSA pathogenesis.

Purpose of the Study:

  • To investigate the functional impact of M1 macrophages on trophoblast behavior in RSA.
  • To elucidate the molecular mechanisms underlying M1-Mφ and trophoblast crosstalk.
  • To identify potential therapeutic targets for RSA.

Main Methods:

  • Established an M1-Mφ-trophoblast coculture system.
  • Quantified CXCL9 expression using qPCR, ELISA, and immunofluorescence.
  • Assessed trophoblast migration and invasion via wound healing and Transwell assays.
  • Conducted rescue experiments and an in vivo animal model.

Main Results:

  • M1-Mφ inhibited trophoblast migration and invasion through CXCL9 release.
  • CXCL9 expression was elevated in RSA decidual tissues.
  • CXCL9 activated the CXCR3-JAK/STAT1 pathway, leading to ZEB1 upregulation via IRF1.
  • ZEB1 promoted CCL2 release, enhancing macrophage recruitment.
  • In vivo, CXCL9 inhibition reduced embryo resorption and macrophage infiltration.

Conclusions:

  • Identified a novel M1-Mφ-mediated mechanism regulating trophoblast function in RSA via the CXCL9/STAT1/IRF1/ZEB1 axis.
  • This axis promotes macrophage recruitment through CCL2, exacerbating RSA.
  • Highlights a new aspect of macrophage-trophoblast interaction in pregnancy complications.
Keywords:
CXCL9EMTM1-Mφmigration and invasionrecurrent spontaneous abortiontrophoblasts

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