Large Number of CD68/CD163 Hofbauer Cells and Characteristic Vascular Structural Alterations in the Placental Villi of Cases with Placenta Accreta Spectrum

Overview

Journal Med Mol Morphol

Publisher Springer

Specialties Cell Biology
Molecular Biology
Pathology

Date 2025 Mar 14

PMID 40082293

Authors

Hazuki Kashiwagi

Kengo Shigehara

Terufumi Kubo

Yoshihiko Hirohashi

Tasuku Mariya

Kazuhiko Matsuo

Tomoyuki Minowa

Shin-Ichi Ishioka

Kenji Murata

Takayuki Kanaseki

Tomohide Tsukahara

Tadashi Hasegawa

Tsuyoshi Saito

Toshihiko Torigoe

Affiliations

Soon will be listed here.

Abstract

Placenta accreta spectrum (PAS) is a serious disease leading to complications and maternal death. The objective of the study was to characterize the placental villi and blood vessels of PAS villi histopathologically. We investigated 10 cases of PAS (five cases of placenta increta, two cases of placenta accreta, and three cases of placenta percreta) histologically. Immunohistochemical staining using anti-CD68 or anti-CD163 antibodies was performed to detect and count Hofbauer cells. Immunohistochemical staining with an anti-CD34 antibody was used to detect vascular endothelial cells, and the number and area of vessels were analyzed. The numbers of CD68-positive or CD163-positive Hofbauer cells were larger in PAS cases compared with control cases. The vascular area in villi was smaller in PAS cases compared with control cases. The number of blood vessels in villi was slightly higher in PAS cases than in control cases. The numbers of Hofbauer cells and vessels in villi were larger in PAS cases compared with control cases, whereas the area of vessels in villi was smaller in PAS cases compared with control cases. Although their biological meaning is elusive, these findings provide novel insights into the pathogenesis of PAS, particularly regarding the role of Hofbauer cells in immune-suppressive role and angiogenesis and the alterations in vascular structure and hemodynamics in the chorionic villi.

References

Silver R, Branch D . Placenta Accreta Spectrum. N Engl J Med. 2018; 378(16):1529-1536. DOI: 10.1056/NEJMcp1709324. View

Hecht J, Baergen R, Ernst L, Katzman P, Jacques S, Jauniaux E . Classification and reporting guidelines for the pathology diagnosis of placenta accreta spectrum (PAS) disorders: recommendations from an expert panel. Mod Pathol. 2020; 33(12):2382-2396. DOI: 10.1038/s41379-020-0569-1. View

Chantraine F, Blacher S, Berndt S, Palacios-Jaraquemada J, Sarioglu N, Nisolle M . Abnormal vascular architecture at the placental-maternal interface in placenta increta. Am J Obstet Gynecol. 2012; 207(3):188.e1-9. DOI: 10.1016/j.ajog.2012.06.083. View

Wu S, Kocherginsky M, Hibbard J . Abnormal placentation: twenty-year analysis. Am J Obstet Gynecol. 2005; 192(5):1458-61. DOI: 10.1016/j.ajog.2004.12.074. View

Kashiwagi H, Mariya T, Umemoto M, Ogawa S, Hirohashi Y, Fujibe Y . Pregnancy-specific beta-1-glycoprotein 6 is a potential novel diagnostic biomarker of placenta accreta spectrum. Med Mol Morphol. 2023; 57(1):35-44. DOI: 10.1007/s00795-023-00371-y. View

Yao Y, Xu X, Jin L . Macrophage Polarization in Physiological and Pathological Pregnancy. Front Immunol. 2019; 10:792. PMC: 6476302. DOI: 10.3389/fimmu.2019.00792. View

Guenther S, Vrekoussis T, Heublein S, Bayer B, Anz D, Knabl J . Decidual macrophages are significantly increased in spontaneous miscarriages and over-express FasL: a potential role for macrophages in trophoblast apoptosis. Int J Mol Sci. 2012; 13(7):9069-9080. PMC: 3430283. DOI: 10.3390/ijms13079069. View

Schonkeren D, van der Hoorn M, Khedoe P, Swings G, van Beelen E, Claas F . Differential distribution and phenotype of decidual macrophages in preeclamptic versus control pregnancies. Am J Pathol. 2011; 178(2):709-17. PMC: 3069820. DOI: 10.1016/j.ajpath.2010.10.011. View

Gonzalez J, Franzke C, Yang F, Romero R, Girardi G . Complement activation triggers metalloproteinases release inducing cervical remodeling and preterm birth in mice. Am J Pathol. 2011; 179(2):838-49. PMC: 3157168. DOI: 10.1016/j.ajpath.2011.04.024. View

10.

Chambers M, Rees A, Cronin J, Nair M, Jones N, Thornton C . Macrophage Plasticity in Reproduction and Environmental Influences on Their Function. Front Immunol. 2021; 11:607328. PMC: 7840613. DOI: 10.3389/fimmu.2020.607328. View

11.

Ingman K, Cookson V, Jones C, Aplin J . Characterisation of Hofbauer cells in first and second trimester placenta: incidence, phenotype, survival in vitro and motility. Placenta. 2010; 31(6):535-44. DOI: 10.1016/j.placenta.2010.03.003. View

12.

Loegl J, Hiden U, Nussbaumer E, Schliefsteiner C, Cvitic S, Lang I . Hofbauer cells of M2a, M2b and M2c polarization may regulate feto-placental angiogenesis. Reproduction. 2016; 152(5):447-55. DOI: 10.1530/REP-16-0159. View

13.

Anteby E, Natanson-Yaron S, Greenfield C, Goldman-Wohl D, Haimov-Kochman R, Holzer H . Human placental Hofbauer cells express sprouty proteins: a possible modulating mechanism of villous branching. Placenta. 2005; 26(6):476-83. DOI: 10.1016/j.placenta.2004.08.008. View

14.

Svensson J, Jenmalm M, Matussek A, Geffers R, Berg G, Ernerudh J . Macrophages at the fetal-maternal interface express markers of alternative activation and are induced by M-CSF and IL-10. J Immunol. 2011; 187(7):3671-82. DOI: 10.4049/jimmunol.1100130. View

15.

Jaiswal M, Mallers T, Larsen B, Kwak-Kim J, Chaouat G, Gilman-Sachs A . V-ATPase upregulation during early pregnancy: a possible link to establishment of an inflammatory response during preimplantation period of pregnancy. Reproduction. 2012; 143(5):713-25. DOI: 10.1530/REP-12-0036. View

16.

Mor G, Cardenas I, Abrahams V, Guller S . Inflammation and pregnancy: the role of the immune system at the implantation site. Ann N Y Acad Sci. 2011; 1221:80-7. PMC: 3078586. DOI: 10.1111/j.1749-6632.2010.05938.x. View

17.

Gustafsson C, Mjosberg J, Matussek A, Geffers R, Matthiesen L, Berg G . Gene expression profiling of human decidual macrophages: evidence for immunosuppressive phenotype. PLoS One. 2008; 3(4):e2078. PMC: 2323105. DOI: 10.1371/journal.pone.0002078. View

18.

Ning F, Liu H, Lash G . The Role of Decidual Macrophages During Normal and Pathological Pregnancy. Am J Reprod Immunol. 2016; 75(3):298-309. DOI: 10.1111/aji.12477. View

19.

Demir R, Erbengi T . Some new findings about Hofbauer cells in the chorionic villi of the human placenta. Acta Anat (Basel). 1984; 119(1):18-26. DOI: 10.1159/000145857. View

20.

Demir R, Kayisli U, Seval Y, Celik-Ozenci C, Korgun E, Demir-Weusten A . Sequential expression of VEGF and its receptors in human placental villi during very early pregnancy: differences between placental vasculogenesis and angiogenesis. Placenta. 2004; 25(6):560-72. DOI: 10.1016/j.placenta.2003.11.011. View