Investigation of PLGF, sFlt-1 Expression in Placenta Previa, Placenta Accreta and Normotensive Placentas in the 3rd Trimester of Pregnancy
Yıl 2024,
Cilt: 21 Sayı: 3, 407 - 414
Gamze Erdoğan
,
Seval Kaya
,
Nurullah Peker
,
İbrahim İbiloğlu
,
Engin Deveci
Öz
Background: We aimed to immunohistochemically examine the expression level of Placental growth factor (PLGF) and Soluble FMS-like tyrosine kinase-1 (sFlt-1) proteins in normotensive, Placenta accreta (PA) and Placenta previa (PP).
Materials and Methods: Three groups were created for the study: 20 Nomotensive placentas, 20 PP and 20 PA from women diagnosed with placenta samples. 4-6 μm thick sections were taken from the placentas, PLGF and sFlt-1 immunostaining were applied to the obtained sections, and their expression intensities and localizations in the tissues were determined.
Results: As a result of our observations, normotensive placenta group; sFlt-1 expression was observed in hofbauer cells and syncytial nodes and PLGF positive expression was observed in nuclei of muscle cells in some tunica media region. PP and PA group; sFlt-1 expression was positive in decidua cells, hofbauer cells and dilated vascular endothelium. PP and PA group; negative PLGF expression was observed in syncytial nodes and positive PLGF expression was observed in hofbauer cells and endothelial cells. There was a significant difference between normotensive, PP and PA groups (p<0.05).
Conclusions: It can be thought that sFlt-1 and PLGF may be important signal stimulators and markers in the trophoblastic degeneration, apoptotic cells, increase in angiogenesis and imbalance in implanta-tion seen in cases of PP and PA.
Proje Numarası
TIP.23.003
Kaynakça
- 1. Knöfler M, Haider S, Saleh L, Pollheimer J, Gamage T. James J. Human placenta and trophoblast development: key molecular mechanisms and model systems. Cell Mol L Sciens. 2019;76(18):3479-96.
- 2. Napso T, Yong HEJ, Lopez-Tello J, Sferruzzi-Perri A. The role of placental hormones in mediating maternal adapta-tions to support pregnancy and lactation. Front Physiol. 2018;9:1091.
- 3. Ahn KH, Lee EH, Cho GJ, Hong SC, Oh MJ, Kim HJ. Anterior placenta previa in the mid-trimester of pregnancy as a risk factor for neonatal respiratory distress syndrome. PloS one. 2018;13(11):e0207061.
- 4. Silver RM. Branch DW, Placenta accreta spectrum. N Eng J Med. 2018;378(16):1529-36.
- 5. Silver RM. Abnormal placentation: placenta previa, vasa previa, and placenta accreta. Obstet Gynecol. 2015;126(3):654-68.
- 6. Jauniaux E, Collins S, Burton GJ. Placenta accreta spec-trum: pathophysiology and evidence-based anatomy for prenatal ultrasound imaging. Am J Obstet Gynecol. 2018;218(1):75-87.
- 7. Morlando M, Sarno L, Napolitano R, Capone A, Tessitore G, Maruotti GM, et al. Placenta accreta: incidence and risk factors in an area with a particularly high rate of cesarean section. Acta Obstet Gynecol Scandinavica. 2013;92(4):457-60.
- 8. Fitzpatrick K, Sellers S, Spark P, Kurinczuk JJ, Brocklehurst P, Knight M. The management and outcomes of placenta accreta, increta, and percreta in the UK: a population‐based descriptive study. Int J Obstet Gynecol. 2014;121(1):62-71.
- 9. Jauniaux E, Bhide A. Prenatal ultrasound diagnosis and outcome of placenta previa accreta after cesarean deliv-ery: a systematic review and meta-analysis. Am J Obstet Gynecol. 2017;217(1):27-36.
- 10. Lecarpentier É, Vieillefosse S, Haddad B, Fournier T, Leguy MC, Guibourdenche J, et al. Placental growth factor (PlGF) and sFlt-1 during pregnancy: physiology, as-say and interest in preeclampsia. Annal Bio Clin. 2016;74(3):259-67.
- 11. Liao L, Zhao X, Zhou M, Deng Y, Li Y, Peng C. sFlt-1: A Double Regulator in Angiogenesis-related Diseases. Cur-rent Pharmaceutical Design. 2021;27(40):4160-70.
- 12. Chau K, Hennessy A, Makris A. Placental growth factor and pre-eclampsia. J Hum Hypert. 2017;31(12):782-6.
- 13. Cai SN, Wu YT, Zeng L, Ding YQ. Value of 3D ultrasound flow imaging combined with serum AFP, β-hCG, sFlt-1 and CK in the diagnosis of placenta accreta. BMC Wom-en's Health. 2022;22(1):556.
- 14. Alessandrini L, Aryananda R, Ariani G, Agustina B, Akbar MİA Dachlan EG, et al. The correlation between serum levels and placental tissue expression of PLGF and sFLT-1 and the FIGO grading of the placenta accreta
spectrum disorders. J Matern Fetal Neonatal Med. 2023;36(1):2183744.
- 15. Seker U, Aktas A, Nergiz Y, Zincircioglu S.B, Ketani M.A. Investigation of the protective effects of melatonin, amifostine (WR-2721), and N-acetylcysteine on radio-therapy-induced uterine tissue injury in rats. Int. J. Radia-tion Research. 2020;18(4): 791-8.
- 16. Seker U, Kavak D.E, Dokumaci F.Z, Kizildag S, Irtegun-Kandemir S. The nephroprotective effect of Quercetin in Cyclophosphamide-induced renal toxicity might be associ-ated with MAPK/ERK and NF-κB signal modulation activi-ty. Drug and Chemical Toxicology. 2024;1-10.
- 17. Sur E, Oznurlu Y, Ozaydın T. The determination of Ghrelin immunoreactivity in gastric mucosa of fundus during pregnancy in mice. Int J Bio Res. 2017;8(12):672-6.
- 18. Lecarpentier E, Zsengellér ZK, Salahuddin S, Covarrubias AE, Lo A, Haddad B, et al. Total versus free placental growth factor levels in the pathogenesis of preeclampsia. Hypertension. 2020;76(3):875-83.
- 19. Stepan H, Hund M, Andraczek T. Combining biomarkers to predict pregnancy complications and redefine preeclamp-sia: the angiogenic-placental syndrome. Hypertension. 2020;75(4):918-26.
- 20. Huhn EA, Kreienbühl A, Hoffmann I, Schoetzau A, Lange S, Martinez de Tejada B, et al. Diagnostic accuracy of differ-ent soluble fms-like tyrosine kinase 1 and placental growth factor cut-off values in the assessment of preterm and term preeclampsia: a gestational age matched case-control study. Frontiers in medicine.
2018;5:325.
- 21. Öztaş E, Özler S, Ergin M, Erel Ö, Güler B, Çağlar AT, et al. Decreased oxidative stress may contribute to the
disease process in placenta accreta. Turk J Med Sci. 2017;47(4):1180-4.
- 22. Andraweera P, Dekker G, Roberts C. The vascular endothe-lial growth factor family in adverse pregnancy outcomes. Human reproduction update. 2012;18(4):436-57.
- 23. Yamashita M, Kumasawa K, Nakamura H, Kimura T. Solu-ble FLT-1 rules placental destiny. Biochemical and bio-physical research communications. 2018;496(4):1243-9.
- 24. McMahon K, Karumanchi SA, Stillman IE, Cummings BSP, Patton D, Easterling T. Does soluble fms-like tyrosine ki-nase-1 regulate placental invasion? Insight from the inva-sive placenta. Am J Obstet Gynecol. 2014;210(1):68.e1-4.
- 25. Lumbanraja S, Yaznil MZ, Siahaan AM, Bancin BEP. Pla-cental Growth Factor-soluble FMS-like Tyrosine Kinase-1 Ratio in Placenta Accreta Spectrum Disorder: Case Control Study. Open Access Macedonian J Med Sci. 2022;10(B):848-52.
- 26. Seval Y, Korgun ET, Demir R. Hofbauer cells in early hu-man placenta: possible implications in vasculogenesis and angiogenesis. Placenta. 2007;28(8-9):841-5.
- 27. Ciğercioğullari E, Filinte D, Toz E, Avci İ, Erdem B, Eminli İ, et al., The determination of normal percentages of syn-cytiotrophoblastic knots in various regions of placenta: where to count the syncytial knots. Turk Patoloji Derg. 2015; 31(1):1-8.
- 28. Özgökçe Ç, Öcal A, Ermiş I.S. Expression of NF-κB and VEGF in normal placenta and placenta previa patients. Advance in Clin. and Exp.Med. 2023;32(3):297-306.
Gebeliğin 3. Trimestrinde Plasenta Previa, Plasenta Akreata ve Normotensif Plasentalarda PLGF, sFlt-1 ekspresyonunun incelenmesi
Yıl 2024,
Cilt: 21 Sayı: 3, 407 - 414
Gamze Erdoğan
,
Seval Kaya
,
Nurullah Peker
,
İbrahim İbiloğlu
,
Engin Deveci
Öz
Amaç: Normotensif, Plasenta akreata (PA) ve Plasenta previa (PP); Plasenta büyüme faktör (PLGF) ve Soluble Fms-Benzeri Tirozin Kinaz-1 (sFlt-1) proteinlerin ekspresyon düzeylerinin immünohistokimyasal olarak incelenmesini amaçladık.
Materyal ve Metod: Çalışmaya 20 Nomotensif plasenta, 20 PP ve 20 PA tanısı konmuş kadına ait plasen-ta örnekleri olmak üzere 3 grup oluşturulmuştur. Plasentalardan 4-6 μm kalınlığında kesitler alındı, elde edilen kesitlere PLGF ve sFlt-1 immün boyama uygulanarak dokulardaki ekspresyon şiddetleri ve loka-lizasyonları belirlendi.
Bulgular: Gözlemlerimiz sonucu normotensif plasenta grubu; hofbauer hücreler ve sinsityal nodlar sFlt-1 ve bazı tunika media bölgesindeki kas hücrelerin nukleuslarında PLGF pozitif ekspresyonu izlendi. PP ve PA grubu; desidua hücreler, hofbauer hücrelerinde ve dilate damar endotelinde sFlt-1 ekspresyonu pozitif izlendi. PP ve PA grubu; sinsityal düğümlerde negatif, hofbauer hücrelerinde ve endotel hücre-lerinde pozitif PLGF ekspresyonu izlendi. Normotensif, PP ve PA grupları arasında anlamlı bir fark vardı (p<0.05).
Sonuç: PP ve PA olgularında görülen trofoblastik dejenerasyon ve apoptotik hücreler, anjiyogenezisin artmasına ve implantasyonda dengesizliğin gerçekleşmesinde sFlt-1 ve PLGF etkili olabileceğini düşün-mekteyiz.
Etik Beyan
Araştırma, Dicle Üniversitesi Tıp Fakültesi Etik Kurulu'nun 17.03.2022 tarih ve 67 sayılı onayı ile başlatılmıştır.
Destekleyen Kurum
Dicle Üniversitesi Bilimsel Araştırma Projeleri Komisyonu Başkanlığı
Proje Numarası
TIP.23.003
Teşekkür
Danışman Hocam Prof.Dr. Engin DEVECİ 'ye Desteklerinden dolayı teşekkürlerimi sunarım.
Kaynakça
- 1. Knöfler M, Haider S, Saleh L, Pollheimer J, Gamage T. James J. Human placenta and trophoblast development: key molecular mechanisms and model systems. Cell Mol L Sciens. 2019;76(18):3479-96.
- 2. Napso T, Yong HEJ, Lopez-Tello J, Sferruzzi-Perri A. The role of placental hormones in mediating maternal adapta-tions to support pregnancy and lactation. Front Physiol. 2018;9:1091.
- 3. Ahn KH, Lee EH, Cho GJ, Hong SC, Oh MJ, Kim HJ. Anterior placenta previa in the mid-trimester of pregnancy as a risk factor for neonatal respiratory distress syndrome. PloS one. 2018;13(11):e0207061.
- 4. Silver RM. Branch DW, Placenta accreta spectrum. N Eng J Med. 2018;378(16):1529-36.
- 5. Silver RM. Abnormal placentation: placenta previa, vasa previa, and placenta accreta. Obstet Gynecol. 2015;126(3):654-68.
- 6. Jauniaux E, Collins S, Burton GJ. Placenta accreta spec-trum: pathophysiology and evidence-based anatomy for prenatal ultrasound imaging. Am J Obstet Gynecol. 2018;218(1):75-87.
- 7. Morlando M, Sarno L, Napolitano R, Capone A, Tessitore G, Maruotti GM, et al. Placenta accreta: incidence and risk factors in an area with a particularly high rate of cesarean section. Acta Obstet Gynecol Scandinavica. 2013;92(4):457-60.
- 8. Fitzpatrick K, Sellers S, Spark P, Kurinczuk JJ, Brocklehurst P, Knight M. The management and outcomes of placenta accreta, increta, and percreta in the UK: a population‐based descriptive study. Int J Obstet Gynecol. 2014;121(1):62-71.
- 9. Jauniaux E, Bhide A. Prenatal ultrasound diagnosis and outcome of placenta previa accreta after cesarean deliv-ery: a systematic review and meta-analysis. Am J Obstet Gynecol. 2017;217(1):27-36.
- 10. Lecarpentier É, Vieillefosse S, Haddad B, Fournier T, Leguy MC, Guibourdenche J, et al. Placental growth factor (PlGF) and sFlt-1 during pregnancy: physiology, as-say and interest in preeclampsia. Annal Bio Clin. 2016;74(3):259-67.
- 11. Liao L, Zhao X, Zhou M, Deng Y, Li Y, Peng C. sFlt-1: A Double Regulator in Angiogenesis-related Diseases. Cur-rent Pharmaceutical Design. 2021;27(40):4160-70.
- 12. Chau K, Hennessy A, Makris A. Placental growth factor and pre-eclampsia. J Hum Hypert. 2017;31(12):782-6.
- 13. Cai SN, Wu YT, Zeng L, Ding YQ. Value of 3D ultrasound flow imaging combined with serum AFP, β-hCG, sFlt-1 and CK in the diagnosis of placenta accreta. BMC Wom-en's Health. 2022;22(1):556.
- 14. Alessandrini L, Aryananda R, Ariani G, Agustina B, Akbar MİA Dachlan EG, et al. The correlation between serum levels and placental tissue expression of PLGF and sFLT-1 and the FIGO grading of the placenta accreta
spectrum disorders. J Matern Fetal Neonatal Med. 2023;36(1):2183744.
- 15. Seker U, Aktas A, Nergiz Y, Zincircioglu S.B, Ketani M.A. Investigation of the protective effects of melatonin, amifostine (WR-2721), and N-acetylcysteine on radio-therapy-induced uterine tissue injury in rats. Int. J. Radia-tion Research. 2020;18(4): 791-8.
- 16. Seker U, Kavak D.E, Dokumaci F.Z, Kizildag S, Irtegun-Kandemir S. The nephroprotective effect of Quercetin in Cyclophosphamide-induced renal toxicity might be associ-ated with MAPK/ERK and NF-κB signal modulation activi-ty. Drug and Chemical Toxicology. 2024;1-10.
- 17. Sur E, Oznurlu Y, Ozaydın T. The determination of Ghrelin immunoreactivity in gastric mucosa of fundus during pregnancy in mice. Int J Bio Res. 2017;8(12):672-6.
- 18. Lecarpentier E, Zsengellér ZK, Salahuddin S, Covarrubias AE, Lo A, Haddad B, et al. Total versus free placental growth factor levels in the pathogenesis of preeclampsia. Hypertension. 2020;76(3):875-83.
- 19. Stepan H, Hund M, Andraczek T. Combining biomarkers to predict pregnancy complications and redefine preeclamp-sia: the angiogenic-placental syndrome. Hypertension. 2020;75(4):918-26.
- 20. Huhn EA, Kreienbühl A, Hoffmann I, Schoetzau A, Lange S, Martinez de Tejada B, et al. Diagnostic accuracy of differ-ent soluble fms-like tyrosine kinase 1 and placental growth factor cut-off values in the assessment of preterm and term preeclampsia: a gestational age matched case-control study. Frontiers in medicine.
2018;5:325.
- 21. Öztaş E, Özler S, Ergin M, Erel Ö, Güler B, Çağlar AT, et al. Decreased oxidative stress may contribute to the
disease process in placenta accreta. Turk J Med Sci. 2017;47(4):1180-4.
- 22. Andraweera P, Dekker G, Roberts C. The vascular endothe-lial growth factor family in adverse pregnancy outcomes. Human reproduction update. 2012;18(4):436-57.
- 23. Yamashita M, Kumasawa K, Nakamura H, Kimura T. Solu-ble FLT-1 rules placental destiny. Biochemical and bio-physical research communications. 2018;496(4):1243-9.
- 24. McMahon K, Karumanchi SA, Stillman IE, Cummings BSP, Patton D, Easterling T. Does soluble fms-like tyrosine ki-nase-1 regulate placental invasion? Insight from the inva-sive placenta. Am J Obstet Gynecol. 2014;210(1):68.e1-4.
- 25. Lumbanraja S, Yaznil MZ, Siahaan AM, Bancin BEP. Pla-cental Growth Factor-soluble FMS-like Tyrosine Kinase-1 Ratio in Placenta Accreta Spectrum Disorder: Case Control Study. Open Access Macedonian J Med Sci. 2022;10(B):848-52.
- 26. Seval Y, Korgun ET, Demir R. Hofbauer cells in early hu-man placenta: possible implications in vasculogenesis and angiogenesis. Placenta. 2007;28(8-9):841-5.
- 27. Ciğercioğullari E, Filinte D, Toz E, Avci İ, Erdem B, Eminli İ, et al., The determination of normal percentages of syn-cytiotrophoblastic knots in various regions of placenta: where to count the syncytial knots. Turk Patoloji Derg. 2015; 31(1):1-8.
- 28. Özgökçe Ç, Öcal A, Ermiş I.S. Expression of NF-κB and VEGF in normal placenta and placenta previa patients. Advance in Clin. and Exp.Med. 2023;32(3):297-306.