Increased mouse double minute X expression in human placental villous macrophages (Hofbauer cells) in gestational diabetes mellitus

Yıl 2021, Cilt: 5 Sayı: 9, 978 - 981, 01.09.2021

Sefa Arlıer , Sadik Kükrer , Cevdet Adıgüzel

https://doi.org/10.28982/josam.900943

Öz

Background/Aim: Gestational diabetes mellitus is a common metabolic problem in pregnancy, and its prevalence ranges between 5-20%. Hofbauer cells are tissue macrophages of the feto-placental component that are raised in the villous tree of the placenta during pregnancy, but their quantity falls off with growing gestational age. We theorize that Hofbauer cells play a significant role in placental pathophysiology in GDM by controlling the MDMX (mouse double minute X/MDM4/HDMX) gene.
Methods: We performed immunohistochemistry on human placental specimens to determine cell-specific expression of MDMX in Hofbauer cells (HC) among the control and GDM (n=8 in each group) groups with matching gestational ages.
Results: Immunohistochemical analysis revealed that MDMXs were secreted by Hofbauer cells in the placental villous tree and compared to the placenta got from normal pregnancies, significantly higher MDMX HSCORE levels were detected in placenta Hofbauer cells (32.8 (24.52) vs. 190.1 (32.54), P=0.001) of the GDM group.
Conclusion: We revealed Hofbauer cells to be a source of MDMX secretion in human placenta. MDM2 levels in Hofbauer cells are also increased in GDM. This study found higher levels of MDMX in the Hofbauer cells from GDM placentas, suggesting an induction of MDMX secretion. GDM interaction in placental Hofbauer cells may contribute to GDM-associated feto-placental complications. Further studies are needed to define the significance of this relationship.

Anahtar Kelimeler

Gestational Diabetes Mellitus, Mouse Double Minute X Expression, Houfbauer cells, Placenta

Kaynakça

• 1. Pantham P, Aye ILMH, Powell TL. Inflammation in maternal obesity and gestational diabetes mellitus. Placenta. 2015 Jul 1;36(7):709–15.
• 2. Sisino G, Bouckenooghe T, Aurientis S, Fontaine P, Storme L, Vambergue A. Diabetes during pregnancy influences Hofbauer cells, a subtype of placental macrophages, to acquire a pro-inflammatory phenotype. Biochim Biophys Acta, Mol Basis Dis. 2013 Dec 1;1832(12):1959–68.
• 3. Grigoriadis C, Tympa A, Creatsa M, Bakas P, Liapis A, Kondi-Pafiti A, Creatsas G. Hofbauer cells morphology and density in placentas from normal and pathological gestations. Rev Bras Ginecol e Obstet [Internet]. 2013 Sep [cited 2021 Mar 20];35(9):407–12. Available from: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-72032013000900005&lng=en&nrm=iso&tlng=en
• 4. Finch RA, Donoviel DB, Potter D, Shi M, Fan A, Freed DD, Wang CY, Zambrowicz BP, Ramirez-Solis R, Sands AT, Zhang N. mdmx is a negative regulator of p53 activity in vivo. Cancer Res. 2002;62(11):3221–5.
• 5. Schonkeren D, Van Der Hoorn ML, Khedoe P, Swings G, Van Beelen E, Claas F, Van Kooten C, De Heer E, Scherjon S. Differential distribution and phenotype of decidual macrophages in preeclamptic versus control pregnancies. Am J Pathol. 2011 Feb 1;178(2):709–17.
• 6. Arlier S, Murk W, Guzeloglu-Kayisli O, Semerci N, Larsen K, Tabak MS, Arici A, Schatz F, Lockwood CJ, Kayisli UA. The extracellular signal-regulated kinase 1/2 triggers angiogenesis in human ectopic endometrial implants by inducing angioblast differentiation and proliferation. Am J Reprod Immunol. 2017;78(6).
• 7. Kim SH, Lee HW, Kim YH, Koo YH, Chae HD, Kim CH, Lee PR, Kang BM. Down-regulation of p21-activated kinase 1 by progestin and its increased expression in the eutopic endometrium of women with endometriosis. Hum Reprod [Internet]. 2009 [cited 2021 Mar 7];24(5):1133–41. Available from: https://academic.oup.com/humrep/article/24/5/1133/711053
• 8. Lee KW, Ching SM, Ramachandran V, Yee A, Hoo FK, Chia YC, Wan Sulaiman WA, Suppiah S, Mohamed MH, Veettil SK. Prevalence and risk factors of gestational diabetes mellitus in Asia: A systematic review and meta-analysis. BMC Pregnancy Childbirth [Internet]. 2018 Dec 14 [cited 2021 Mar 1];18(1):1–20. Available from: https://doi.org/10.1186/s12884-018-2131-4
• 9. Basmaeil YS, Al Subayyil AM, Khatlani T, Bahattab E, Al-Alwan M, Abomaray FM, Kalionis B, Alshabibi MA, Alaskar AS, Abumaree MH. Human chorionic villous mesenchymal stem/stromal cells protect endothelial cells from injury induced by high level of glucose. Stem Cell Res Ther [Internet]. 2018 Sep 21 [cited 2021 Mar 1];9(1):238. Available from: https://pubmed.ncbi.nlm.nih.gov/30241570/
• 10. Gonzalez E, Jawerbaum A. Diabetic Pregnancies: The Challenge of Developing in a Pro-Inflammatory Environment. Curr Med Chem [Internet]. 2006 Jul 24 [cited 2021 Mar 2];13(18):2127–38. Available from: https://pubmed.ncbi.nlm.nih.gov/16918343/
• 11. Radaelli T, Varastehpour A, Catalano P, Hauguel-De Mouzon S. Gestational Diabetes Induces Placental Genes for Chronic Stress and Inflammatory Pathways. Diabetes [Internet]. 2003 Dec [cited 2021 Mar 2];52(12):2951–8. Available from: https://pubmed.ncbi.nlm.nih.gov/14633856/
• 12. Chen B, Ge Y, Wang H, Zhu H, Xu J, Wu Z, Tang S. Expression of mitofusin 2 in placentae of women with gestational diabetes mellitus. J Genet [Internet]. 2018 Dec 1 [cited 2021 Mar 2];97(5):1289–94. Available from: https://link.springer.com/article/10.1007/s12041-018-1030-9
• 13. Barke TL, Goldstein JA, Sundermann AC, Reddy AP, Linder JE, Correa H, Velez-Edwards DR, Aronoff DM. Gestational diabetes mellitus is associated with increased CD163 expression and iron storage in the placenta. Am J Reprod Immunol [Internet]. 2018 Oct 1 [cited 2021 Mar 2];80(4):e13020. Available from: https://pubmed.ncbi.nlm.nih.gov/29984475/
• 14. Qi S, Wang X. Decreased expression of miR-185 in serum and placenta of patients with gestational diabetes mellitus. Clin Lab [Internet]. 2019 [cited 2021 Mar 2];65(12):2361–7. Available from: https://pubmed.ncbi.nlm.nih.gov/31850721/
• 15. Reyes L, Golos TG. Hofbauer cells: Their role in healthy and complicated pregnancy [Internet]. Vol. 9, Frontiers in Immunology. Frontiers Media S.A.; 2018 [cited 2021 Mar 1]. p. 2628. Available from: https://www.frontiersin.org/article/10.3389/fimmu.2018.02628/full
• 16. Chun CZ, Sood R, Ramchandran R. Vasculogenesis and Angiogenesis. In 2016. p. 77–99.
• 17. Regnault TRH, Galan HL, Parker TA, Anthony R V. Placental development in normal and compromised pregnancies - A review. Placenta. 2002;23(SUPPL. 1).
• 18. Zulu MZ, Martinez FO, Gordon S, Gray CM. The Elusive Role of Placental Macrophages: The Hofbauer Cell [Internet]. Vol. 11, Journal of Innate Immunity. S. Karger AG; 2019 [cited 2021 Mar 2]. p. 447–56. Available from: https://pubmed.ncbi.nlm.nih.gov/30970346/
• 19. Yu J, Zhou Y, Gui J, Li AZ, Su XL, Feng L. Assessment of the number and function of macrophages in the placenta of gestational diabetes mellitus patients. J Huazhong Univ Sci Technol - Med Sci [Internet]. 2013 Oct 1 [cited 2021 Mar 2];33(5):725–9. Available from: https://pubmed.ncbi.nlm.nih.gov/24142727/
• 20. Chen X, Gohain N, Zhan C, Lu WY, Pazgier M, Lu W. Structural basis of how stress-induced MDMX phosphorylation activates p53. Oncogene. 2016 Apr 14;35(15):1919–25.
• 21. Heazell AEP, Sumathi GM, Bhatti NR. What investigation is appropriate following maternal perception of reduced fetal movements? J Obstet Gynaecol (Lahore) [Internet]. 2005 Oct 1 [cited 2021 Mar 3];25(7):648–50. Available from: https://pubmed.ncbi.nlm.nih.gov/16263536/