Hofbauer cells in pregnancies complicated by gestational diabetes mellitus and pathological fetal growth
Author(s)
Type
Journal Article
Abstract
Problem
Gestational diabetes mellitus (GDM) increases the risk of large-for-gestational-age (LGA) birth and long-term cardiometabolic complications in offspring, particularly in males. These outcomes are associated with altered placental vascularisation, but the underlying mechanisms remain poorly defined. Hofbauer cells (HBCs) are fetal-origin macrophages located in the villous stroma with established roles in immune regulation and vascularisation.
Method of Study
This study investigated whether HBC abundance and phenotype are associated with fetal growth, fetal sex, and placental vascularisation in term placentae from non-GDM and GDM pregnancies. Pan-macrophage (CD14, CD68), HBC-enriched (FOLR2, VSIG4), M1 (CD86), and M2 (CD163, MRC1) markers were assessed by RT-qPCR and quantitative immunohistochemistry.
Results
In both non-GDM and GDM placentae, all markers, except CD86 were detected, supporting an M2-like HBC phenotype. In GDM placentae, the number of pan-macrophage (CD68), HBC-enriched (FOLR2), and M2-associated (CD163, MRC1) cells were reduced in terminal villi compared with non-GDM controls (p < 0.05; n = 13 non-GDM; n = 12 GDM), indicating reduced HBC abundance without phenotypic switching. Reduced expression of HBC-enriched (FOLR2, VSIG4) and M2-associated (CD163) transcripts supported these findings (p < 0.05; n = 18 non-GDM; n = 19 GDM). No further differences were observed following stratification by fetal growth or sex. HBC-related gene expression correlated positively with the endothelial marker PECAM1/CD31, in both non-GDM and GDM placentae (r ≥ 0.5, p < 0.05).
Conclusions
HBCs abundance is reduced in GDM placentae independently of fetal growth or sex, whilst HBC phenotype is preserved. Reduced HBC abundance may contribute to placental vascular alterations that are characteristic of GDM.
Gestational diabetes mellitus (GDM) increases the risk of large-for-gestational-age (LGA) birth and long-term cardiometabolic complications in offspring, particularly in males. These outcomes are associated with altered placental vascularisation, but the underlying mechanisms remain poorly defined. Hofbauer cells (HBCs) are fetal-origin macrophages located in the villous stroma with established roles in immune regulation and vascularisation.
Method of Study
This study investigated whether HBC abundance and phenotype are associated with fetal growth, fetal sex, and placental vascularisation in term placentae from non-GDM and GDM pregnancies. Pan-macrophage (CD14, CD68), HBC-enriched (FOLR2, VSIG4), M1 (CD86), and M2 (CD163, MRC1) markers were assessed by RT-qPCR and quantitative immunohistochemistry.
Results
In both non-GDM and GDM placentae, all markers, except CD86 were detected, supporting an M2-like HBC phenotype. In GDM placentae, the number of pan-macrophage (CD68), HBC-enriched (FOLR2), and M2-associated (CD163, MRC1) cells were reduced in terminal villi compared with non-GDM controls (p < 0.05; n = 13 non-GDM; n = 12 GDM), indicating reduced HBC abundance without phenotypic switching. Reduced expression of HBC-enriched (FOLR2, VSIG4) and M2-associated (CD163) transcripts supported these findings (p < 0.05; n = 18 non-GDM; n = 19 GDM). No further differences were observed following stratification by fetal growth or sex. HBC-related gene expression correlated positively with the endothelial marker PECAM1/CD31, in both non-GDM and GDM placentae (r ≥ 0.5, p < 0.05).
Conclusions
HBCs abundance is reduced in GDM placentae independently of fetal growth or sex, whilst HBC phenotype is preserved. Reduced HBC abundance may contribute to placental vascular alterations that are characteristic of GDM.
Date Issued
2026-02-01
Date Acceptance
2026-01-05
Citation
American Journal of Reproductive Immunology, 2026, 95 (2)
ISSN
1046-7408
Publisher
Wiley
Journal / Book Title
American Journal of Reproductive Immunology
Volume
95
Issue
2
Copyright Statement
© 2026 The Author(s). American Journal of Reproductive Immunology published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41691616
Subjects
GDM
Hofbauer cells
LGA
gestational diabetes mellitus
macrophages
placenta
Humans
Female
Pregnancy
Diabetes, Gestational
Fetal Development
Macrophages
Placenta
Adult
Antigens, CD
Male
Biomarkers
Publication Status
Published
Coverage Spatial
Denmark
Article Number
e70216
Date Publish Online
2026-02-15