Online first
Research paper
Published online: 2024-01-31

open access

Page views 227
Article views/downloads 173
Get Citation

Connect on Social Media

Connect on Social Media

The discrepancy distribution of macrophage subsets in preeclampsia placenta with or without fetal growth restriction from a small cohort

Wenhui Song1, Fengjiao Wang1, Xia Li1, Fangfang Liu1, Tianxiao Yu1, Xizhenzi Fan1, Mingwei Li1, Qing Guo12

Abstract

Objectives: To identify the effect of distribution characteristic of macrophages on placental function and angiogenesis in pregnancies with preeclampsia (PE) in presence of fetal growth restriction (FGR) or preeclampsia without FGR. Material and methods: The study tested the hypothesis that there was association between distribution characteristic of macrophage subsets (marked by CD68, CD163, respectively) and placental capillary development, leading to placental dysfunction in PE pregnancies with FGR (n = 36). Changes in placental parameters related with efficiency and angiogenesis and macrophage phenotypes (CD68 and CD163) were evaluated by immunohistochemistry. Pearson correlation analysis was performed to analysis the association between macrophage phenotype and placental function as well the CD34 staining, respectively. Additionally, the localization of CD68 and CD163 was assessed by using immunoflurorescence staining. Results: Pearson correlation analysis had shown the positive association between CD68 expression and microvessel formation and the reverse linear relationship between CD163 staining and placental sufficiency in PE + FGR placenta. The co-localization of CD163 and CD34 may pointed to the compensatory role of CD163 distribution involved in prompting neovascularization. Conclusions: The association between disturbed distribution of macrophages and placental efficiency and angiogenesis were only found in PE with FGR not in PE pregnancies without FGR, underlying the discrepancy role of macrophage subsets depending on the clinical phenotype of PE pregnancies.

Article available in PDF format

View PDF Download PDF file

References

  1. Wu JL, Jia J, He MZ, et al. Placental Origins of Preeclampsia: Potential Therapeutic Targets. Curr Med Sci. 2019; 39(2): 190–195.
  2. Raguema N, Moustadraf S, Bertagnolli M. Immune and Apoptosis Mechanisms Regulating Placental Development and Vascularization in Preeclampsia. Front Physiol. 2020; 11: 98.
  3. Sánchez-Aranguren LC, Prada CE, Riaño-Medina CE, et al. Endothelial dysfunction and preeclampsia: role of oxidative stress. Front Physiol. 2014; 5: 372.
  4. Michalczyk M, Celewicz A, Celewicz M, et al. The Role of Inflammation in the Pathogenesis of Preeclampsia. Mediators Inflamm. 2020; 2020: 3864941.
  5. Aisagbonhi O, Morris GP. Human Leukocyte Antigens in Pregnancy and Preeclampsia. Front Genet. 2022; 13: 884275.
  6. Laskowska M, Laskowska K, Oleszczuk J. Interleukin-18 concentrations in pregnancies complicated by preeclampsia with and without IUGR: A comparison with normotensive pregnant women with isolated IUGR and healthy pregnant women. Pregnancy Hypertens. 2011; 1(3-4): 206–212.
  7. Leavey K, Grynspan D, Cox BJ. Both "canonical" and "immunological" preeclampsia subtypes demonstrate changes in placental immune cell composition. Placenta. 2019; 83: 53–56.
  8. Brown MB, von Chamier M, Allam AB, et al. M1/M2 macrophage polarity in normal and complicated pregnancy. Front Immunol. 2014; 5: 606.
  9. Egbor M, Ansari T, Morris N, et al. Morphometric placental villous and vascular abnormalities in early- and late-onset pre-eclampsia with and without fetal growth restriction. BJOG. 2006; 113(5): 580–589.
  10. Mayhew TM, Wijesekara J, Baker PN, et al. Morphometric evidence that villous development and fetoplacental angiogenesis are compromised by intrauterine growth restriction but not by pre-eclampsia. Placenta. 2004; 25(10): 829–833.
  11. Liang G, Zhou C, Jiang X, et al. De novo generation of macrophage from placenta-derived hemogenic endothelium. Dev Cell. 2021; 56(14): 2121–2133.e6.
  12. Loegl J, Hiden U, Nussbaumer E, et al. Hofbauer cells of M2a, M2b and M2c polarization may regulate feto-placental angiogenesis. Reproduction. 2016; 152(5): 447–455.
  13. Durst JK, Tuuli MG, Stout MJ, et al. Degree of obesity at delivery and risk of preeclampsia with severe features. Am J Obstet Gynecol. 2016; 214(5): 651.e1–651.e5.
  14. Medeiros LTL, Peraçoli JC, Bannwart-Castro CF, et al. Monocytes from pregnant women with pre-eclampsia are polarized to a M1 phenotype. Am J Reprod Immunol. 2014; 72(1): 5–13.
  15. Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin Summary, Number 222. Obstet Gynecol. 2020; 135(6): 1492–1495.
  16. Vayssière C, Sentilhes L, Ego A, et al. Fetal growth restriction and intra-uterine growth restriction: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians. Eur J Obstet Gynecol Reprod Biol. 2015; 193: 10–18.
  17. Marques MR, Grandi C, Nascente LM, et al. Placental morphometry in hypertensive disorders of pregnancy and its relationship with birth weight in a Latin American population. Pregnancy Hypertens. 2018; 13: 235–241.
  18. Kalra J, Dragowska WH, Bally MB. Using Pharmacokinetic Profiles and Digital Quantification of Stained Tissue Microarrays as a Medium-Throughput, Quantitative Method for Measuring the Kinetics of Early Signaling Changes Following Integrin-Linked Kinase Inhibition in an In Vivo Model of Cancer. J Histochem Cytochem. 2015; 63(9): 691–709.
  19. Mao Q, Chu S, Shapiro S, et al. Increased placental expression of angiotensin-converting enzyme 2, the receptor of SARS-CoV-2, associated with hypoxia in twin anemia-polycythemia sequence (TAPS). Placenta. 2021; 105: 7–13.
  20. Seo H, Bazer FW, Burghardt RC, et al. Immunohistochemical Examination of Trophoblast Syncytialization during Early Placentation in Sheep. Int J Mol Sci. 2019; 20(18).
  21. Erlebacher A. Immunology of the maternal-fetal interface. Annu Rev Immunol. 2013; 31: 387–411.
  22. Miller D, Motomura K, Galaz J, et al. Cellular immune responses in the pathophysiology of preeclampsia. J Leukoc Biol. 2022; 111(1): 237–260.
  23. Yang SW, Cho EH, Choi SoY, et al. DC-SIGN expression in Hofbauer cells may play an important role in immune tolerance in fetal chorionic villi during the development of preeclampsia. J Reprod Immunol. 2017; 124: 30–37.
  24. Milosevic-Stevanovic J, Krstic M, Radovic-Janosevic D, et al. Number of decidual natural killer cells & macrophages in pre-eclampsia. Indian J Med Res. 2016; 144(6): 823–830.
  25. Nakao S, Noda K, Zandi S, et al. VAP-1-mediated M2 macrophage infiltration underlies IL-1β- but not VEGF-A-induced lymph- and angiogenesis. Am J Pathol. 2011; 178(4): 1913–1921.
  26. Ito Y, Matsuoka K, Uesato T, et al. Increased expression of perforin, granzyme B, and C5b-9 in villitis of unknown etiology. Placenta. 2015; 36(5): 531–537.
  27. Bezemer RE, Schoots MH, Timmer A, et al. Altered Levels of Decidual Immune Cell Subsets in Fetal Growth Restriction, Stillbirth, and Placental Pathology. Front Immunol. 2020; 11: 1898.
  28. Vinnars MTN, Rindsjö E, Ghazi S, et al. The number of CD68(+) (Hofbauer) cells is decreased in placentas with chorioamnionitis and with advancing gestational age. Pediatr Dev Pathol. 2010; 13(4): 300–304.
  29. Jetten N, Verbruggen S, Gijbels MJ, et al. Anti-inflammatory M2, but not pro-inflammatory M1 macrophages promote angiogenesis in vivo. Angiogenesis. 2014; 17(1): 109–118.
  30. Lash GE, Pitman H, Morgan HL, et al. Decidual macrophages: key regulators of vascular remodeling in human pregnancy. J Leukoc Biol. 2016; 100(2): 315–325.
  31. Liu X, Fei H, Yang C, et al. Trophoblast-Derived Extracellular Vesicles Promote Preeclampsia by Regulating Macrophage Polarization. Hypertension. 2022; 79(10): 2274–2287.