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ADM AND SFLT-1 EXPRESSION IN PLACENTAS WITH GESTATIONAL DIABETES MELLITUS

Year 2023, Volume: 6 Issue: 1, 161 - 168, 30.04.2023
https://doi.org/10.36516/jocass.1269105

Abstract

Amaç: Bu çalışmada gestasyonel diyabetes mellitusta (GDM) vasküler regülasyonda rolü saptanan iki yeni protein olan Adrenomedullin (ADM) ve soluble fms-benzeri tirozin kinaz (sFlt-1)’in ekspresyon seviyelerini incelemeyi, hastalığın histopatolojisinde bu proteinlerin ekspresyon seviyelerini karşılaştırmayı ve bu proteinlerin ekspresyon yoğunluğunun hastalıkla korelasyonunu gözlemlemeyi amaçladık.
Gereç ve Yöntem: Çalışmamızda 20 Normotansif ve 20 GDM’li plasenta örneği alındı. Histolojik takip yöntemiyle takip edildi. Bu dokulardan 5µm kalınlığında kesitler alınarak Hematoksilen-Eozin, Periodic Acid Schiff (PAS) boyamaları yapıldı. İmmunünohistokimyasal olarak ADM ve sFlt-1 antikorları çalışıldı.
Bulgular: GDM grubunda; kök villuslarındaki kan damarlarında dilatasyon ve konjesyon, endotel hücrelerinde hiperplazi görüldü. Villusların dış kısmındaki sinsitiyal köprülerde artış, mononükleer hücre infiltrasyonu, maternal bölgedeki desidual hücrelerin bazılarında piknotik nükleuslar ve sitoplazma kaybı izlendi. İmmunohistokimyasal incelemede villusların sitotrofoblast ve sinsitiyotrofoblast hücrelerinde ve sinsitiyal düğümlerde negatif ADM ekspresyonu vardı. Küçük villusların bazı sitotrofoblast hücrelerinde, damar endotel hücrelerinde ve desidual hücrelerde pozitif ADM ekspresyonu görüldü. GDM grubunda sFlt-1 ekspresyonu endotel hücrelerinde, mezenşimal bağ doku içindeki bazı Hofbauer hücrelerinde, desidual hücre nükleuslarında ve membranlarında pozitif olarak gözlendi.
Sonuç: Desidual hücre membranlarında, sitotrofoblastlarda ADM pozitif ekspresyon gösterdiğinden ADM’nin glikoz yoğunluğunun belirlenmesinde ve bununla ilişkili olarak insülin regülasyonunda önemli bir düzenleyici olabileceğini düşündürmüştür. Yine sFlt-1’in maternal ve fötal bölgelerdeki endotel hücresi üzerindeki etkileri ve Hofbauer hücrelerindeki ekspresyonu, anjiyogenik etkide bu molekülün anahtar rol alabileceği kanısını uyandırmıştır.

Supporting Institution

Dicle Üniversitesi Bilimsel Araştırma Projeleri Komisyonu

Project Number

TIP.18.032

References

  • 1. Hod M, Kapur A, Sacks DA, et al. The International Federation of Gynecology and Obstetrics (FIGO) Initiative on gestational diabetes mellitus: A pragmatic guide for diagnosis, management, and care. Int J Gynaecol Obstet. 2015;131 Suppl 3:173-211. https://doi.org/10.1016/S0020-7292(15)30033-3
  • 2. Cvitic S, Desoye G, Hiden U. Glucose, insulin, and oxygen interplay in placental hypervascularisation in diabetes mellitus. Biomed Res Int. 2014;2014:145846. https://doi.org/10.1155/2014/145846
  • 3. Pardo F, Arroyo P, Salomón C, et al. Role of equilibrative adenosine transporters and adenosine receptors as modulators of the human placental endothelium in gestational diabetes mellitus. Placenta. 2013;34(12):1121-27. https://doi.org/10.1016/j.placenta.2013.09.007
  • 4. Wadsack C, Desoye G, Hiden U. The feto-placental endothelium in pregnancy pathologies. Wien Med Wochenschr. 2012;162(9-10):220-24. https://doi.org/10.1007/s10354-012-0075-2
  • 5. Gauster M, Desoye G, Tötsch M, et al. The placenta and gestational diabetes mellitus. Curr Diab Rep. 2012;12(1):16-23. https://doi.org/10.1007/s11892-011-0244-5
  • 6. Dong Y, Betancourt A, Belfort M, et al. Targeting Adrenomedullin to Improve Lipid Homeostasis in Diabetic Pregnancies. J Clin Endocrinol Metab. 2017;102(9):3425-36. https://doi.org/10.1210/jc.2017-00920
  • 7. Di Iorio R, Marinoni E, Urban G, et al. Fetomaternal adrenomedullin levels in diabetic pregnancy. Horm Metab Res. 2001;33(8):486-90. https://doi.org/10.1055/s-2001-16942
  • 8. Farina A, Eklund E, Bernabini D, et al. A First-Trimester Biomarker Panel for Predicting the Development of Gestational Diabetes. Reprod Sci. 2017;24(6):954-59. https://doi.org/10.1177/1933719116675057
  • 9. Romero R, Erez O, Hüttemann M, et al. Metformin, the aspirin of the 21st century: its role in gestational diabetes mellitus, prevention of preeclampsia and cancer, and the promotion of longevity. Am J Obstet Gynecol. 2017;217(3):282-302. https://doi.org/10.1016/j.ajog.2017.06.003
  • 10. Aktaş A, Aşır F, Başaran SO, et al. Granulocyte colony stimulating factor (GCSF) protected in ovarian tissues against ischemia-reperfusion injury. Journal of Drug Delivery and Therapeutics. 2022;12(4):26-30. https://doi.org/10.22270/jddt.v12i4.5538
  • 11. Calderon IM, Damasceno DC, Amorin RL, et al. Morphometric study of placental villi and vessels in women with mild hyperglycemia or gestational or overt diabetes. Diabetes research and clinical practice, (2007);78(1), 65-71. https://doi.org/10.1016/j.diabres.2007.01.023
  • 12. Metzger BE, Buchanan TA, Coustan DR, et al. Summary and recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes Care. 2007;30 Suppl 2:251-60. https://doi.org/10.2337/dc07-s22513.
  • 13. Radaelli T, Varastehpour A, Catalano P, et al. Gestational diabetes induces placental genes for chronic stress and inflammatory pathways. Diabetes. 2003;52(12):2951-8. https://doi.org/10.2337/diabetes.52.12.2951
  • 14. Hauguel-de Mouzon S, Guerre-Millo M. The placenta cytokine network and inflammatory signals. Placenta. 2006;27(8):794-8. https://doi.org/10.1016/j.placenta.2005.08.009
  • 15. Jarmuzek P, Wielgos M, Bomba-Opon D. Placental pathologic changes in gestational diabetes mellitus. Neuro Endocrinol Lett. 2015;36(2):101-5.
  • 16. Sela S, Itin A, Natanson-Yaron S, et al. A novel human-specific soluble vascular endothelial growth factor receptor 1: cell type-specific splicing and implications to vascular endothelial growth factor homeostasis and preeclampsia. Circulation research. 2008;102(12):1566-74. https: /doi.org/1/ 0.1161/CIRCRESAHA.108.171504
  • 17. Desoye G. Hauguel-de mouzon S. The human placenta in gestational diabetes mellitus. Diabetes care. 2007;30:120-6. https://doi.org/10.2337/dc07-s203
  • 18. Asmussen I. Ultrastructure of the villi and fetal capillaries in placentas from smoking and nonsmoking mothers. BJOG: An International Journal of Obstetrics & Gynaecology. 1980;87(3):239-45. https://doi.org/10.1111/j.1471-0528.1980.tb04527.x
  • 19. Gheorman L, Pleşea I, Gheorman V. Histopathological considerations of placenta in pregnancy with diabetes. Rom J Morphol Embryol. 2012;53(2):329-36.
  • 20. Li N, Pan X, Zhang J, et al. Plasma levels of miR-137 and miR-124 are associated with Parkinson’s disease but not with Parkinson’s disease with depression. Neurological Sciences. 2017;38:761-7. https://doi.org/10.1007/s10072-017-2841-9
  • 21. Janota J, Pomyje J, Toth D, et al. Expression of angiopoietic factors in normal and type-I diabetes human placenta: a pilot study. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2003;111(2):153-6. https://doi.org/10.1016/S0301-2115(03)00204-5
  • 22. Dong Y, Banadakoppa M, Chauhan M, et al. Circulating adrenomedullin is elevated in gestational diabetes and its role in impaired insulin production by β-cells. The Journal of Clinical Endocrinology and Metabolism. 2019;104(3):697-706. https://doi.org/10.1210/jc.2018-01119
  • 23. Maynard SE, Min JY, Merchan J, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003;111(5):649-658. https://doi.org/10.1172/JCI17189.
  • 24. Kanenishi K, Kuwabara H, Ueno M, et al. Immunohistochemical adrenomedullin expression is decreased in the placenta from pregnancies with pre‐eclampsia. Pathology international. 2000;50(7):536-40. https://doi.org/10.1046/j.1440-1827.2000.01085.x

ADM and SFLT-1 Expression in Placentas with Gestational Diabetes Mellitus

Year 2023, Volume: 6 Issue: 1, 161 - 168, 30.04.2023
https://doi.org/10.36516/jocass.1269105

Abstract

Aim: In this study, we aimed to examine the expression levels of Adrenomedullin (ADM) and soluble fms-like tyrosine kinase-1 (sFlt-1), two novel proteins found to be involved in vascular regulation in gestational diabetes mellitus (GDM), to compare the expression levels of these proteins in the histopathology of the disease and to observe the correlation of the expression intensity of these proteins with the disease.
Methods: In our study, 20 healthy and 20 GDM placenta samples were obtained. Histologic follow-up was performed. 5µm thick sections were taken from these tissues and stained with Hematoxylin-Eosin and Periodic Acid Schiff (PAS). Immunohistochemically, ADM and sFlt-1 antibodies were studied.
Results: In the GDM group, vascular dilatation and congestion in stem villus, hyperplasic endothelial cells, and increased syncytial bridges in the external part of the villi, mononuclear cell infiltration, pyknotic nuclei and cytoplasm loss in some of the decidual cells in the maternal region were observed. In the immunohistochemical examination, cytotrophoblast and syncytiotrophoblast cells of villous and syncytial nodes showed negative ADM expression. ADM was positively expressed in some cytotrophoblast cells of small villi, vascular endothelial cells and decidual cells. In the GDM group, sFlt-1 expression was positive in endothelial cells, some Hofbauer cells of mesenchymal connective tissue, decidual cell nuclei and membranes.
Conclusion: ADM may be an important receptor in insulin metabolism to determine the glucose level because we found positive ADM expression in cytotrophoblasts and membranes of decidual cells. In addition, changes in endothelial cells of maternal and fetal regions and sFlt-1 expression in Hofbauer cells suggest that this molecule possibly plays a key role in the angiogenic effect.

Project Number

TIP.18.032

References

  • 1. Hod M, Kapur A, Sacks DA, et al. The International Federation of Gynecology and Obstetrics (FIGO) Initiative on gestational diabetes mellitus: A pragmatic guide for diagnosis, management, and care. Int J Gynaecol Obstet. 2015;131 Suppl 3:173-211. https://doi.org/10.1016/S0020-7292(15)30033-3
  • 2. Cvitic S, Desoye G, Hiden U. Glucose, insulin, and oxygen interplay in placental hypervascularisation in diabetes mellitus. Biomed Res Int. 2014;2014:145846. https://doi.org/10.1155/2014/145846
  • 3. Pardo F, Arroyo P, Salomón C, et al. Role of equilibrative adenosine transporters and adenosine receptors as modulators of the human placental endothelium in gestational diabetes mellitus. Placenta. 2013;34(12):1121-27. https://doi.org/10.1016/j.placenta.2013.09.007
  • 4. Wadsack C, Desoye G, Hiden U. The feto-placental endothelium in pregnancy pathologies. Wien Med Wochenschr. 2012;162(9-10):220-24. https://doi.org/10.1007/s10354-012-0075-2
  • 5. Gauster M, Desoye G, Tötsch M, et al. The placenta and gestational diabetes mellitus. Curr Diab Rep. 2012;12(1):16-23. https://doi.org/10.1007/s11892-011-0244-5
  • 6. Dong Y, Betancourt A, Belfort M, et al. Targeting Adrenomedullin to Improve Lipid Homeostasis in Diabetic Pregnancies. J Clin Endocrinol Metab. 2017;102(9):3425-36. https://doi.org/10.1210/jc.2017-00920
  • 7. Di Iorio R, Marinoni E, Urban G, et al. Fetomaternal adrenomedullin levels in diabetic pregnancy. Horm Metab Res. 2001;33(8):486-90. https://doi.org/10.1055/s-2001-16942
  • 8. Farina A, Eklund E, Bernabini D, et al. A First-Trimester Biomarker Panel for Predicting the Development of Gestational Diabetes. Reprod Sci. 2017;24(6):954-59. https://doi.org/10.1177/1933719116675057
  • 9. Romero R, Erez O, Hüttemann M, et al. Metformin, the aspirin of the 21st century: its role in gestational diabetes mellitus, prevention of preeclampsia and cancer, and the promotion of longevity. Am J Obstet Gynecol. 2017;217(3):282-302. https://doi.org/10.1016/j.ajog.2017.06.003
  • 10. Aktaş A, Aşır F, Başaran SO, et al. Granulocyte colony stimulating factor (GCSF) protected in ovarian tissues against ischemia-reperfusion injury. Journal of Drug Delivery and Therapeutics. 2022;12(4):26-30. https://doi.org/10.22270/jddt.v12i4.5538
  • 11. Calderon IM, Damasceno DC, Amorin RL, et al. Morphometric study of placental villi and vessels in women with mild hyperglycemia or gestational or overt diabetes. Diabetes research and clinical practice, (2007);78(1), 65-71. https://doi.org/10.1016/j.diabres.2007.01.023
  • 12. Metzger BE, Buchanan TA, Coustan DR, et al. Summary and recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes Care. 2007;30 Suppl 2:251-60. https://doi.org/10.2337/dc07-s22513.
  • 13. Radaelli T, Varastehpour A, Catalano P, et al. Gestational diabetes induces placental genes for chronic stress and inflammatory pathways. Diabetes. 2003;52(12):2951-8. https://doi.org/10.2337/diabetes.52.12.2951
  • 14. Hauguel-de Mouzon S, Guerre-Millo M. The placenta cytokine network and inflammatory signals. Placenta. 2006;27(8):794-8. https://doi.org/10.1016/j.placenta.2005.08.009
  • 15. Jarmuzek P, Wielgos M, Bomba-Opon D. Placental pathologic changes in gestational diabetes mellitus. Neuro Endocrinol Lett. 2015;36(2):101-5.
  • 16. Sela S, Itin A, Natanson-Yaron S, et al. A novel human-specific soluble vascular endothelial growth factor receptor 1: cell type-specific splicing and implications to vascular endothelial growth factor homeostasis and preeclampsia. Circulation research. 2008;102(12):1566-74. https: /doi.org/1/ 0.1161/CIRCRESAHA.108.171504
  • 17. Desoye G. Hauguel-de mouzon S. The human placenta in gestational diabetes mellitus. Diabetes care. 2007;30:120-6. https://doi.org/10.2337/dc07-s203
  • 18. Asmussen I. Ultrastructure of the villi and fetal capillaries in placentas from smoking and nonsmoking mothers. BJOG: An International Journal of Obstetrics & Gynaecology. 1980;87(3):239-45. https://doi.org/10.1111/j.1471-0528.1980.tb04527.x
  • 19. Gheorman L, Pleşea I, Gheorman V. Histopathological considerations of placenta in pregnancy with diabetes. Rom J Morphol Embryol. 2012;53(2):329-36.
  • 20. Li N, Pan X, Zhang J, et al. Plasma levels of miR-137 and miR-124 are associated with Parkinson’s disease but not with Parkinson’s disease with depression. Neurological Sciences. 2017;38:761-7. https://doi.org/10.1007/s10072-017-2841-9
  • 21. Janota J, Pomyje J, Toth D, et al. Expression of angiopoietic factors in normal and type-I diabetes human placenta: a pilot study. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2003;111(2):153-6. https://doi.org/10.1016/S0301-2115(03)00204-5
  • 22. Dong Y, Banadakoppa M, Chauhan M, et al. Circulating adrenomedullin is elevated in gestational diabetes and its role in impaired insulin production by β-cells. The Journal of Clinical Endocrinology and Metabolism. 2019;104(3):697-706. https://doi.org/10.1210/jc.2018-01119
  • 23. Maynard SE, Min JY, Merchan J, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003;111(5):649-658. https://doi.org/10.1172/JCI17189.
  • 24. Kanenishi K, Kuwabara H, Ueno M, et al. Immunohistochemical adrenomedullin expression is decreased in the placenta from pregnancies with pre‐eclampsia. Pathology international. 2000;50(7):536-40. https://doi.org/10.1046/j.1440-1827.2000.01085.x
There are 24 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Articles
Authors

Necat Arslan 0000-0002-5703-9892

Sevda Soker 0000-0001-6453-0033

Süreyya Özdemir Başaran 0000-0003-0734-2428

Özge Kaplan 0000-0001-5203-9650

Fırat Aşır 0000-0002-6384-9146

Engin Deveci 0000-0002-2353-1184

Uğur Şeker 0000-0002-1693-6378

Project Number TIP.18.032
Publication Date April 30, 2023
Acceptance Date April 19, 2023
Published in Issue Year 2023 Volume: 6 Issue: 1

Cite

APA Arslan, N., Soker, S., Özdemir Başaran, S., Kaplan, Ö., et al. (2023). ADM and SFLT-1 Expression in Placentas with Gestational Diabetes Mellitus. Journal of Cukurova Anesthesia and Surgical Sciences, 6(1), 161-168. https://doi.org/10.36516/jocass.1269105

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