陈振烈;曹羽明;张铭;张元珍;

• 1:武汉大学中南医院妇产科
• 2:湖北省产前诊断与优生临床医学研究中心

摘要(Abstract)：

目的:检测Wnt2在植入胎盘组织中的表达,分析Wnt2对滋养细胞凋亡、迁移和侵袭功能的影响。方法:收集2020年7月至2021年1月于武汉大学中南医院妇产科行剖宫产的胎盘植入孕产妇胎盘组织15例(植入组)和正常孕产妇胎盘组织15例(对照组)。RT-PCR法和Western blot法检测胎盘组织中Wnt2表达水平,采用siRNA敲低HTR-8/Svneo细胞中Wnt2表达水平,流式细胞学法检测细胞凋亡,Transwell侵袭和迁移实验评估细胞的迁移和侵袭能力,RT-PCR法和Western blot法检测β-catenin、Bcl-2、Caspase-3、MMP-2和MMP-9表达水平。结果:与对照组相比,植入组胎盘组织中Wnt2、MMP-2和MMP-9 mRNA和蛋白表达量均显著升高(均P<0.05)。转染敲低HTR-8/Svneo细胞Wnt2水平后,细胞凋亡率显著增加(P<0.05),细胞迁移和侵袭能力显著抑制(P<0.01),β-catenin、Bcl-2、MMP-2和MMP-9表达显著下降(均P<0.05),而Caspase-3表达显著升高(P<0.05)。结论:植入胎盘组织中Wnt2蛋白表达显著升高,且Wnt2可能通过wnt/β-catenin信号通路参与了胎盘滋养细胞的凋亡、迁移和侵袭。

关键词(KeyWords)： Wnt2;胎盘植入;滋养细胞;迁移;侵袭

Abstract:

Keywords:

基金项目(Foundation):

作者(Authors): 陈振烈;曹羽明;张铭;张元珍;

DOI: 10.13283/j.cnki.xdfckjz.2022.02.002

参考文献(References)：

• [1] 中华医学会围产医学分会，中华医学会妇产科学分会产科学组.胎盘植入诊治指南(2015)[J].中华产科急救电子杂志，2016,5(1):26-31
• [2] 王芊芸，黄贝尔，杨慧霞.胎盘植入发病机制的研究进展[J].中华围产医学杂志，2019,22(1):66-69
• [3] Shainker SA,Coleman B,Timor-Tritsch IE,et al.Special Report of the Society for Maternal-Fetal Medicine Placenta Accreta Spectrum Ultrasound Marker Task Force:Consensus on definition of markers and approach to the ultrasound examination in pregnancies at risk for placenta accreta spectrum[J].Am J Obstet Gynecol,2021,224(1):B2-b14
• [4] Fonseca A,Ayres de Campos D.Maternal morbidity and mortality due to placenta accreta spectrum disorders[J].Best Pract Res Clin Obstet Gynaecol,2021,72:84-91
• [5] Committee opinion no.529:placenta accreta[J].Obstet Gynecol,2012,120(1):207-211
• [6] Jauniaux E,Kingdom JC,Silver RM.A comparison of recent guidelines in the diagnosis and management of placenta accreta spectrum disorders[J].Best Pract Res Clin Obstet Gynaecol,2021,72:102-116
• [7] Bloomfield V,Rogers S,Leyland N.Placenta accreta spectrum[J].Cmaj,2020,192(34):E980
• [8] Duzyj CM,Buhimschi IA,Motawea H,et al.The invasive phenotype of placenta accreta extravillous trophoblasts associates with loss of E-cadherin[J].Placenta,2015,36(6):645-651
• [9] Gajos-Michniewicz A,Czyz M.WNT Signaling in Melanoma[J].Int J Mol Sci,2020,21(14):4852
• [10] Zhang Y,Wang X.Targeting the Wnt/β-catenin signaling pathway in cancer[J].J Hematol Oncol,2020,13(1):165
• [11] Zhan T,Rindtorff N,Boutros M.Wnt signaling in cancer[J].Oncogene,2017,36(11):1461-1473
• [12] Matsuoka K,Bakiri L,Wolff LI,et al.Wnt signaling and Loxl2 promote aggressive osteosarcoma[J].Cell Res,2020,30(10):885-901
• [13] Martin-Orozco E,Sanchez-Fernandez A,Ortiz-Parra I,et al.WNT signaling in tumors:the way to evade drugs and immunity[J].Front Immunol,2019,10:2854
• [14] Unterleuthner D,Neuhold P,Schwarz K,et al.Cancer-associated fibroblast-derived WNT2 increases tumor angiogenesis in colon cancer[J].Angiogenesis,2020,23(2):159-177
• [15] Kramer N,Schmollerl J,Unger C,et al.Autocrine WNT2 signaling in fibroblasts promotes colorectal cancer progression[J].Oncogene,2017,36(39):5460-5472
• [16] Zhao HJ,Chang HM,Klausen C,et al.Bone morphogenetic protein 2 induces the activation of WNT/β-catenin signaling and human trophoblast invasion through up-regulating BAMBI[J].Cell Signal,2020,67:109489
• [17] Bao H,Liu D,Xu Y,et al.Hyperactivated Wnt-β-catenin signaling in the absence of sFRP1 and sFRP5 disrupts trophoblast differentiation through repression of Ascl2[J].BMC Biol,2020,18(1):151
• [18] Takahashi H,Ogoyama M,Nagayama S,et al.Extravillous trophoblast invasion accelerated by WNT3A,5A,and 10B via CD44[J].J Matern Fetal Neonatal Med,2019:1-9
• [19] Wu S,Kocherginsky M,Hibbard JU.Abnormal placentation:twenty-year analysis[J].Am J Obstet Gynecol,2005,192(5):1458-1461
• [20] Sonderegger S,Pollheimer J,Knofler M.Wnt signalling in implantation,decidualisation and placental differentiation-review[J].Placenta,2010,31(10):839-847
• [21] Monkley SJ,Delaney SJ,Pennisi DJ,et al.Targeted disruption of the Wnt2 gene results in placentation defects[J].Development,1996,122(11):3343-3353
• [22] Boyer A,Goff AK,Boerboom D.WNT signaling in ovarian follicle biology and tumorigenesis[J].Trends Endocrinol Metab,2010,21(1):25-32
• [23] Li N,Li S,Wang Y,et al.Decreased expression of WNT2 in villi of unexplained recurrent spontaneous abortion patients may cause trophoblast cell dysfunction via downregulated Wnt/β-catenin signaling pathway[J].Cell Biol Int,2017,41(8):898-907
• [24] Kocarslan S,Incebiyik A,Guldur ME,et al.What is the role of matrix metalloproteinase-2 in placenta percreta?[J].J Obstet Gynaecol Res,2015,41(7):1018-1022
• [25] Sonderegger S,Haslinger P,Sabri A,et al.Wingless (Wnt)-3A induces trophoblast migration and matrix metalloproteinase-2 secretion through canonical Wnt signaling and protein kinase B/AKT activation[J].Endocrinol,2010,151(1):211-220
• [26] Zeng Y,Wei L,Lali MS,et al.miR-150-5p mediates extravillous trophoblast cell migration and angiogenesis functions by regulating VEGF and MMP9[J].Placenta,2020,93:94-100
• [27] Jauniaux E,Collins S,Burton GJ.Placenta accreta spectrum:pathophysiology and evidence-based anatomy for prenatal ultrasound imaging[J].Am J Obstet Gynecol,2018,218(1):75-87
• [28] Tantbirojn P,Crum CP,Parast MM.Pathophysiology of placenta creta:the role of decidua and extravillous trophoblast[J].Placenta,2008,29(7):639-645