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Updated: Jul 9, 2026
Isolation of Primary Human Decidual Cells from the Fetal Membranes of Term Placentae
Published on: April 30, 2018
Immune activation induced by FOLR2+ decidual macrophage deficiency impairs decidualization and angiogenesis in
Si-Man Chen1, Meng-Ying Li1, Yi-Xing Yang1
1Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Shanghai, China.
Background:
Decidual macrophages maintain immune tolerance and support decidualization at the maternal-fetal interface. However, the heterogeneity and functions of macrophage subsets in recurrent spontaneous abortion (RSA) remain unclear.
Methods:
We integrated single-cell RNA sequencing of human endometrium and decidua with clinical validation. Functional assays using THP-1-derived macrophages and the co-culture with decidual stromal cells were performed to characterize macrophage subsets and investigate their roles in decidualization and RSA pathogenesis.
Results:
A subset of FOLR2+ macrophages enriched in the decidua showed an M2-like immunoregulatory phenotype. In RSA decidua, FOLR2 expression and the proportion of FOLR2+ macrophages were markedly reduced, accompanied by increased inflammatory signaling and impaired angiogenic and adhesion interactions. Functional assays showed that FOLR2 overexpression enhanced immunoregulatory, tissue-resident, and pro-angiogenic properties, whereas FOLR2 silencing promoted inflammatory responses and impaired angiogenesis. Reciprocal crosstalk between DSCs and FOLR2+ macrophages established a positive feedback loop that promoted stromal decidualization and supported pregnancy maintenance.
Conclusions:
FOLR2+ macrophages represent an immunoregulatory subset at the maternal-fetal interface with tissue-resident and pro-angiogenic features. The loss of FOLR2+ macrophages in RSA may contribute to immune dysregulation and defective decidualization, providing new insights into the immune mechanisms underlying RSA pathogenesis.
