The features of the E-cadherin/β-catenin signaling pathway in the placenta and peripheral blood of pregnant women with fetal growth restriction
- 作者: Krasnyi A.M.1, Khachaturyan A.A.1, Tyutyunnik V.L.1, Sorokina L.E.1, Kan N.E.1, Borisova A.G.1, Krasnova L.D.2, Sorivko E.R.3
-
隶属关系:
- Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
- N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
- Melitopol Regional Perinatal Center
- 期: 编号 5 (2025)
- 页面: 48-55
- 栏目: Original Articles
- URL: https://journals.eco-vector.com/0300-9092/article/view/685538
- DOI: https://doi.org/10.18565/aig.2025.43
- ID: 685538
如何引用文章
开放存取
##reader.subscriptionAccessGranted##
详细
It is known that reduced placental size, abnormal development of placental villi and reduced E-cadherin expression are observed in pregnancies with fetal growth restriction.
Objective: To identify the features of the E-cadherin/β-catenin signaling pathway in the placenta and peripheral blood of pregnant women by determining expression of the MMP-9, CCND1 and BIRC5 genes induced by the nuclear β-catenin translocation, as well as WNT2 gene expression, and to analyze the features of apoptosis of the placental cells.
Materials and methods: The study included 82 patients. The main group consisted of 46 women with the postnatal diagnosis of fetal growth restriction without hypertension complications. The control group consisted of 36 patients with normal pregnancy. Investigation of the features of the E-cadherin/β-catenin signaling pathway was carried out by determining expression of the MMP-9, CCND1 and BIRC5 genes induced by the nuclear β-catenin translocation, and WNT2 gene expression in the placental tissue and peripheral blood, as well as analyzing the features of apptosis of placental cells.
Results: It was found that MMP-9 and BIRC5 expression levels in the placenta were significantly higher in fetal growth restriction (p=0.03 and p=0.02, respectively). MMP-9 expression level in the peripheral blood was lower in fetal growth restriction (p=0.001). Increased apoptosis of the placental cells was observed in fetal growth restriction (p=0.03). Excessive apoptosis of trophoblast cells was in fetal growth restriction compared with normal pregnancy (p=0.017).
Conclusion: Lower level of E-cadherin expression in the placenta in fetal growth restriction can be associated with activation of the E-cadherin/β-catenin signaling pathway and development of apoptosis of placental trophoblast cells.
全文:
作者简介
Aleksey Krasnyi
Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
编辑信件的主要联系方式.
Email: alexred@list.ru
ORCID iD: 0000-0001-7883-2702
PhD, Head of the Cytology Laboratory
俄罗斯联邦, MoscowAnuta Khachaturyan
Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: x.anyt37@mail.ru
ORCID iD: 0009-0007-3767-9343
PhD student
俄罗斯联邦, MoscowVictor Tyutyunnik
Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: tioutiounnik@mail.ru
ORCID iD: 0000-0002-5830-5099
SPIN 代码: 1963-1359
Professor, Dr. Med. Sci., Leading Researcher at the Center of Scientific and Clinical Researches
俄罗斯联邦, MoscowLeia Sorokina
Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: leya.sorokina@mail.ru
ORCID iD: 0000-0002-1862-6816
Junior Researcher at the Cytology Laboratory
俄罗斯联邦, MoscowNatalia Kan
Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: kan-med@mail.ru
ORCID iD: 0000-0001-5087-5946
SPIN 代码: 5378-8437
Dr. Med. Sci., Honored Scientist of the Russian Federation, Deputy Director of Science
俄罗斯联邦, MoscowAnastasia Borisova
Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: vvv92@list.ru
ORCID iD: 0009-0004-5234-1584
PhD student
俄罗斯联邦, MoscowLidia Krasnova
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Email: li.kr.2402@gmail.com
ORCID iD: 0009-0009-2718-3672
5th year student of the Institute of Clinical Medicine, majoring in General Medicine
俄罗斯联邦, MoscowEvgeny Sorivko
Melitopol Regional Perinatal Center
Email: awwgxtf@gmail.com
obstetrician-gynecologist
俄罗斯联邦, Melitopol参考
- Министерство здравоохранения Российской Федерации. Клинические рекомендации. Недостаточный рост плода, требующий предоставления медицинской помощи матери (задержка роста плода). 2022. [Ministry of Health of the Russian Federation. Clinical guidelines. Insufficient growth of the fetus, requiring the provision of medical care to the mother (fetal growth retardation). 2022. (in Russian)].
- Gęca T., Stupak A., Nawrot R., Goździcka-Józefiak A., Kwaśniewska A., Kwaśniewski W. Placental proteome in late-onset of fetal growth restriction. Mol. Med. Rep. 2022; 26(6): 356. https://dx.doi.org/10.3892/ mmr.2022.12872
- Malhotra A., Allison B.J., Castillo-Melendez M., Jenkin G., Polglase G.R., Miller S.L. Neonatal morbidities of fetal growth restriction: pathophysiology and impact. Front. Endocrinol. (Lausanne). 2019; 10: 55. https://dx.doi.org/10.3389/fendo.2019.00055
- Закурина А.Н., Павлова Н.Г. Внутриплацентарный кровоток в III триместре беременности, осложненной плацентарной недостаточностью. Журнал акушерства и женских болезней. 2014; 63(5): 51-7. [Zakurina A.N., Pavlova N.G. Intraplacental blood flow in third trimester of placental insufficiency pregnancy. Journal of Obstetrics and Women's Diseases. 2014; 63(5): 51-7. (in Russian)]. https://dx.doi.org/10.17816/JOWD63551-57
- Knöfler M, Pollheimer J. Human placental trophoblast invasion and differentiation: A particular focus on Wnt signaling. Front. Genet. 2013; 4: 190. https://dx.doi.org/10.3389/fgene.2013.00190
- Matsuura K., Jigami T., Taniue K., Morishita Y., Adachi S., Senda T. et al. Identification of a link between Wnt/β-catenin signalling and the cell fusion pathway. Nat. Commun. 2011; 2: 548. https://dx.doi.org/10.1038/ ncomms1551
- Aoki M., Mieda M., Ikeda T., Hamada Y., Nakamura H., Okamoto H. R-spondin3 is required for mouse placental development. Dev. Biol. 2007; 301(1): 218-26. https://dx.doi.org/10.1016/j.ydbio.2006.08.018
- Clevers H., Nusse R. Wnt/b-catenin signaling and disease. Cell. 2012; 149(6): 1192-205. https://dx.doi.org/10.1016/j.cell.2012.05.012
- Liu J., Xiao Q., Xiao J., Niu C., Li Y., Zhang X. et al. Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities. Signal Transduct. Target Ther. 2022; 7(1): 3. https://dx.doi.org/10.1038/s41392-021-00762-6
- Sonderegger S., Husslein H., Leisser C., Knöfler M. Complex expression pattern of Wnt ligands and frizzled receptors in human placenta and its trophoblast subtypes. Placenta. 2007; 28 Suppl A(Suppl A): S97-S102. https://dx.doi.org/10.1016/j.placenta.2006.11.003
- Du W., Liu X., Fan G., Zhao X., Sun Y., Wang T. et al. From cell membrane to the nucleus: an emerging role of E-cadherin in gene transcriptional regulation. J. Cell. Mol. Med. 2014; 18(9): 1712-9. https://dx.doi.org/10.1111/ jcmm.12340
- Xu W., Kimelman D. Mechanistic insights from structural studies of β-catenin and its binding partners. J. Cell Sci. 2007; 120(Pt 19): 3337-44. https://dx.doi.org/10.1242/jcs.013771
- Красный А.М., Хачатурян А.А., Кан Н.Е., Хачатрян З.В., Тютюнник В.Л., Волгина Н.Е., Ганичкина М.Б., Мантрова Д.А., Садекова А.А. Роль Е-кадгерина в формировании задержки роста плода. Акушерство и гинекология. 2018; 6: 38-43. [Krasnyi A.M., Khachaturyan A.A., Kan N.E., Khachatryan Z.V., Tyutyunnik V.L., Volgina N.E., Ganichkina M.B., Mantrova D.A., Sadekova A.A. The role of E-kadherin in the formation of intrauterine growth restriction. Obstetrics and Gynecology. 2018; (6): 38-43. (in Russian)]. https://dx.doi.org/10.18565/aig.2018.6.38-43
- Han H.J., Kwon H.Y., Sohn E.J., Ko H., Kim B., Jung K. et al. Suppression of E-cadherin mediates gallotannin induced apoptosis in Hep G2 hepatocelluar carcinoma cells. Int. J. Biol. Sci. 2014; 10(5): 490-9. https://dx.doi.org/10.7150/ijbs.7495
- Sola I.M., Karin-Kujundzic V., Paic F., Lijovic L., Glibo M., Serman N. et al. WNT5A, β-catenin and SUFU expression patterns, and the significance of microRNA deregulation in placentas with intrauterine growth restriction. Mol. Med. Rep. 2023; 27(2): 28. https://dx.doi.org/10.3892/mmr.2022.12914
- Sola I.M., Serman A., Karin-Kujundzic V., Paic F., Skrtic A., Slatina P. et al. Dishevelled family proteins (DVL1-3) expression in intrauterine growth restriction (IUGR) placentas. Bosn. J. Basic Med. Sci. 2021; 21(4): 447-53. https://dx.doi.org/10.17305/bjbms.2020.5422
- Gan X.Q., Wang J.Y., Xi Y., Wu Z.L., Li Y.P., Li L. Nuclear Dvl, c-Jun, beta-catenin, and TCF form a complex leading to stabilization of beta-catenin-TCF interaction. J. Cell Biol. 2008; 180(6): 1087-100. https://dx.doi.org/10.1083/jcb.200710050
- Manicone A.M., McGuire J.K. Matrix metalloproteinases as modulators of inflammation. Semin. Cell Dev. Biol. 2008; 19(1): 34-41. https://dx.doi.rg/10.1016/j.semcdb.2007.07.003
- Crocker I.P., Cooper S., Ong S.C., Baker P.N. Differences in apoptotic susceptibility of cytotrophoblasts and syncytiotrophoblasts in normal pregnancy to those complicated with preeclampsia and intrauterine growth restriction. Am. J. Pathol. 2003; 162(2): 637-43. https://dx.doi.org/10.1016/ S0002-9440(10)63857-6
- Smith S.C., Baker P.N., Symonds E.M. Increased placental apoptosis in intrauterine growth restriction. Am. J. Obstet. Gynecol. 1997; 177(6): 1395-401. https://dx.doi.org/10.1016/s0002-9378(97)70081-4
- Ishihara N., Matsuo H., Murakoshi H., Laoag-Fernandez J.B., Samoto T., Maruo T. Increased apoptosis in the syncytiotrophoblast in human term placentas complicated by either preeclampsia or intrauterine growth retardation. Am. J. Obstet. Gynecol. 2002; 186(1): 158-66. https://dx.doi.org/10.1067/mob.2002.119176
补充文件
