Altered placental macrophage numbers and subsets in pregnancies complicated with intrahepatic cholestasis of pregnancy (ICP) compared to healthy pregnancies

Altered placental macrophage numbers and subsets in pregnancies complicated with intrahepatic cholestasis of pregnancy (ICP) compared to healthy pregnancies

Intrahepatic cholestasis of pregnancy (ICP) can result in adverse outcomes for both mother and fetus. Inflammatory (M1 subset) or anti-inflammatory (M2 subset) macrophage polarisation is associated with various complications of pregnancy. However, the influence of ICP on macrophage numbers and polar...

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Bibliographic Details
Published in:Placenta (Eastbourne) Vol. 153; pp. 22 - 30
Main Authors: Brenøe, J.E., van Hoorn, E.G.M., Beck, L., Bulthuis, M., Bezemer, R.E., Gordijn, S.J., Schoots, M.H., Prins, J.R.
Format: Journal Article
Language:English
Published: Netherlands Elsevier Ltd 01-08-2024
Subjects:
Adult
Case-Control Studies
Cholestasis, Intrahepatic - blood
Cholestasis, Intrahepatic - immunology
Cholestasis, Intrahepatic - metabolism
Cholestasis, Intrahepatic - pathology
Female
Humans
Immunology
Intrahepatic cholestasis of pregnancy (ICP)
Macrophages
Macrophages - immunology
Macrophages - metabolism
Macrophages - pathology
Placenta - immunology
Placenta - metabolism
Placenta - pathology
Pregnancy
Pregnancy Complications - immunology
Pregnancy Complications - pathology
Ursodeoxycholic Acid - therapeutic use
Intrahepatic cholestasis of pregnancy (ICP)
Pregnancy
Immunology
Macrophages
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Summary:Intrahepatic cholestasis of pregnancy (ICP) can result in adverse outcomes for both mother and fetus. Inflammatory (M1 subset) or anti-inflammatory (M2 subset) macrophage polarisation is associated with various complications of pregnancy. However, the influence of ICP on macrophage numbers and polarisation remains unknown. This study analyses macrophage density and distribution in placentas of patients with ICP compared to controls. Clinical parameters were correlated to macrophage distribution and ursodeoxycholic acid use (UDCA). This study included routinely collected placental tissue samples of 42 women diagnosed with ICP and of 50 control pregnancies. Immunohistochemical staining was performed on placental tissue using CD68 antibody as a pan-macrophage marker, CD206 antibody as an M2 and HLA-DR antibody as an M1 macrophage marker. Macrophage density (cells/mm2) and distribution (CD206+/CD68+ or CD206+/CD68+HLA-DR+) in both decidua (maternal tissue) and villous parenchyma (fetal tissue) were compared between groups. Macrophage density and distribution were correlated to clinical parameters for ICP patients. The density of CD68+ macrophages differed significantly between groups in villous parenchyma. In both decidua and villous parenchyma, CD206+/CD68+ ratio was significantly lower in ICP patients compared to controls (p = 0.003 and p=<0.001, respectively). No difference was found based on UDCA use or in CD68+HLA-DR+ cell density. Significant correlations were found between macrophage density and peak serum bile acids and liver enzymes. In ICP patients, an immune shift was observed in both decidual and villous tissue, indicated by a lower CD206+/CD68+ ratio. ICP seems to affect placental tissue, however more research is required to understand its consequences. [Display omitted] •Increased numbers of macrophages in the villous parenchyma tissue of ICP patients.•A lower CD206/CD68 ratio in placentas of ICP patients.•A positive correlation between serum bile acid concentration and macrophage numbers.•A positive correlation between serum ASAT/ALAT concentration and macrophage numbers.
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ISSN:0143-4004
1532-3102
1532-3102
DOI:10.1016/j.placenta.2024.05.129