基于TGF-β1和E-Cad表达调控及相关信号通路探讨胚胎停育的发生机制

doi:10.3760/cma.j.cn441417-20250123-14004

国际医药卫生导报 ›› 2025, Vol. 31 ›› Issue (14): 2305-2309.DOI: 10.3760/cma.j.cn441417-20250123-14004

基于TGF-β1和E-Cad表达调控及相关信号通路探讨胚胎停育的发生机制

王冬亮刘玉玲

郑州大学第二附属医院妇产科，郑州 450001

收稿日期:2025-01-23 出版日期:2025-07-01 发布日期:2025-08-04
通讯作者: 刘玉玲，Email：562969399@qq.com
基金资助:
河南省医学科技攻关计划（LHGJ20200412）

Exploration on mechanism of embryo damage based on TGF-β1, E-Cad, and related signaling pathways

Wang Dongliang, Liu Yuling

Department of Obstetrics and Gynecology, Second Hospital, Zhengzhou University, Zhengzhou 450001, China

Received:2025-01-23 Online:2025-07-01 Published:2025-08-04
Contact: Liu Yuling, Email: 562969399@qq.com
Supported by:
Problem-tackling Plan of Medical Science and Technology in Henan (LHGJ20200412)

摘要/Abstract

摘要：

目的　基于转化生长因子β1（TGF-β1）和E钙黏蛋白（E-Cad）表达调控及相关信号通路探讨胚胎停育的发生机制。方法　采用成组设计研究，于2024年2月至11月完成。取处于合适孕期且确认胚胎停育的大鼠，分离其胎盘滋养细胞。构建TGF-β1过表达的滋养细胞，采用荧光定量聚合酶联反应检测细胞中的TGF-β1、E-Cad、Smad依赖信号通路（Smad2、Smad3、Smad4）和非Smad依赖信号通路［磷脂酰肌醇3-激酶（PI3K）］，并观察Smad信号激活剂（SRI-011381）、PI3K激活剂（740Y-P）对E-Cad表达的影响，采用单因素方差分析、t检验进行统计分析。结果　pcDNA3.1-TGF-β1组TGF-β1、Smad2、Smad3、Smad4、PI3K mRNA水平均高于正常组（3.15±0.21比1.00±0.15、2.12±0.19比1.00±0.13、1.94±0.22比1.00±0.09、1.73±0.20比1.00±0.14、1.98±0.24比1.00±0.11），E-Cad mRNA水平低于正常组（0.51±0.08比1.00±0.12）；SRI-011381组Smad2、Smad3、Smad4 mRNA水平均高于正常组（2.58±0.22比1.00±0.13、2.27±0.24比1.00±0.15、2.04±0.19比1.00±0.11），E-Cad mRNA水平低于正常组（0.47±0.07比1.00±0.09）；740Y-P组PI3K mRNA水平高于正常组（2.36±0.20比1.00±0.12），E-Cad mRNA水平低于正常组（0.55±0.09比1.00±0.08）；上述指标组间比较差异均有统计学意义（均P<0.05）。结论　TGF-β1可能通过激活Smad与PI3K信号通路，降低E-Cad表达，从而抑制胚胎停育。

关键词: 转化生长因子β1, E钙黏蛋白, 胚胎停育, Smad信号通路, 磷脂酰肌醇3-激酶信号通路

Abstract: Objective　To explore the mechanism of embryo damage based on transforming growth factor β1 (TGF-β1), E-cadherin (E-Cad), and related signaling pathways. Methods　The group design study was performed between February and November 2024. The rats with embryo damage during suitable pregnancy were selected to isolate placental trophocytes. The trophocytes with TGF-β1 overexpresssion were constructed. TGF-β1, E-Cad, Smad-dependent signaling pathways (Smad2, Smad3, Smad4), and non-Smad-dependent signaling pathway [phosphatidylinositol 3-kinase (PI3K)] in the cells were detected by the fluorescence quantitative polymerase chain reaction. The effects of Smad signal activator (SRI-011381) and PI3K activator (740Y-P) on E-Cad were observed. One-way analysis of variance and independent sample t test were used for the statistical analysis. Results　The levels of TGF-β1, Smad2, Smad3, Smad4, and PI3K mRNA in the pcDNA3.1-TGF-β1 group were all higher than those in the normal group (3.15±0.21 vs. 1.00±0.15, 2.12±0.19 vs. 1.00±0.13, 1.94±0.22 vs. 1.00±0.09, 1.73±0.20 vs. 1.00±0.14, and 1.98±0.24 vs. 1.00±0.11), while the level of E-Cad mRNA was lower (0.51±0.08 vs 1.00±0.12). The levels of Smad2, Smad3, and Smad4 mRNA in the SRI-011381 group were higher than those in the normal group (2.58±0.22 vs. 1.00±0.13, 2.27±0.24 vs. 1.00±0.15, and 2.04±0.19 vs. 1.00±0.11), while the level of E-Cad mRNA was lower (0.47±0.07 vs. 1.00±0.09). The level of PI3K mRNA in the 740Y-P group was higher than that in the normal group (2.36±0.20 vs. 1.00±0.12), while the level of E-Cad mRNA was lower (0.55±0.09 vs. 1.00±0.08). There were statistical differences in the above indicators between the groups (all P<0.05). Conclusion　TGF-β1 may inhibit the expression of E-Cad activating Smad and PI3K signaling pathways, and inhibit embryo damage.

Key words: Transforming growth factor β1, , E-cadherin, , Embryo damage, , Smad signaling pathway, , Phosphatidylinositol 3-kinase signaling pathway

王冬亮刘玉玲.

基于TGF-β1和E-Cad表达调控及相关信号通路探讨胚胎停育的发生机制 [J]. 国际医药卫生导报, 2025, 31(14): 2305-2309.

Wang Dongliang, Liu Yuling.

Exploration on mechanism of embryo damage based on TGF-β1, E-Cad, and related signaling pathways [J]. International Medicine and Health Guidance News, 2025, 31(14): 2305-2309.

参考文献

[1]李肖华,石子佳,王俊霞,等.胚胎停育患者绒毛组织染色体检测分析[J].山东医药, 2023, 63(36): 1-4. DOI:10.3969/j.issn.1002-266X.2023.36.001.

[2]赵晓娟,魏珂,董菲,等. 8693例育龄期女性胚胎停育发生率及影响因素分析[J].海南医学, 2023, 34(14):2075-2078. DOI:10.3969/j.issn.1003-6350.2023.14.023.

[3]李苗苗,江洪,蔡朋达.胚胎停育的影响因素分析及预测研究[J].国际生殖健康/计划生育杂志, 2024, 43(4):332-337. DOI:10.12280/gjszjk.20240148.

[4]黄凌佳,杨舒奇,孙欣,等.从分子生物学角度探究胚胎停育相关影响因素的研究进展[J].中国生育健康杂志, 2021, 32(1):79-82. DOI:10.3969/j.issn.1671-878X.2021.01.020.

[5]Trinh QD, Pham NTK, Takada K, et al. Roles of TGF-beta1 in viral infection during pregnancy: research update and perspectives[J]. Int J Mol Sci, 2023, 24(7):6489. DOI: 10.3390/ijms24076489.

[6]马琨,张川.调控TGF-β1-PI3K/AKT轴对骨肉瘤细胞恶性增殖和干性表达的影响[J].国际医药卫生导报, 2023, 29(19): 2750-2756. DOI:10.3760/cma.j.issn.1007-1245.2023.19.019.

[7]Dirisipam K, Madduru D, Jahan P, et al.TGF-beta1 promoter functional gene polymorphism -509 C/T in the maternal susceptibility to recurrent pregnancy loss in South Indian women[J]. Hum Immunol, 2024, 86(1): 111182. DOI:10.1016/j.humimm.2024.111182.

[8]Mohammadzadeh M, Anbari F, Aghaei S, et al. Does combination of estradiol and sesame oil improve the oocyte quality, embryo development and expressions of Zp3, E-cad, and Ctnnb1 genes in mice? An experimental study[J]. Int J Reprod Biomed, 2021, 19(8):707-714. DOI:10.18502/ijrm.v19i8.9618.

[9]王冬亮,胡滨,刘玉玲. TGF-β1和E-Cad的表达对胚胎停育的影响[J].中国卫生检验杂志, 2019, 29(11): 1372-1374, 1378.

[10]董艺超.Let-7b在胚胎停育发生中的作用及分子机制的研究[D].北京:北京协和医学院,2019.DOI:10.27648/d.cnki.gzxhu.2019.000722.

[11]王静,李芬霞,郑艳丽.汉黄芩素调控Akt/mTOR通路对流产大鼠滋养层细胞凋亡及自噬的影响[J].中国优生与遗传杂志, 2023, 31(11): 2206-2211. DOI:10.13404/j.cnki.cjbhh.2023.11.030.

[12]朱融慧,程艳香. TGF-β超家族信号在复发性流产中的研究进展[J].医学研究杂志, 2024, 53(4):181-184. DOI:10.11969/j.issn.1673-548X.2024.04.034.

[13]Martinez CA, Cambra JM, Lucas X, et al. Intrauterine infusion of TGF-beta 1 prior to insemination, alike seminal plasma, influences endometrial cytokine responses but does not impact the timing of the progression of pre-implantation pig embryo development[J]. Biology (Basel), 2021, 10(2): 159. DOI:10.3390/biology10020159.

[14]Kay N, Huang CY, Shiu LY, et al. TGF-beta1 neutralization improves pregnancy outcomes by restoring endometrial receptivity in mice with adenomyosis[J]. Reprod Sci, 2021, 28(3):877-887. DOI:10.1007/s43032-020-00308-1.

[15]崔莉,刘杰,邹歌,等. TNF-α和TGF-β1在胚胎停育患者蜕膜组织中的表达[J].重庆医学, 2024, 53(6): 861-865, 871. DOI:10.3969/j.issn.1671-8348.2024.06.011.

[16]Xue H, Jiang J, Gao J, et al. Correlation of TGF-beta signaling pathway gene polymorphisms with unexplained recurrent spontaneous abortio[J]. Medicine (Baltimore), 2023, 102(43): e35697. DOI:10.1097/MD.0000000000035697.

[17]王维,唐静,杨永红,等.妊娠期高血压疾病患者胎盘组织叶酸代谢基因MTR的表达水平及其作用机制研究[J].现代检验医学杂志, 2022, 37(4): 134-138, 173. DOI:10.3969/j.issn.1671-7414.2022.04.026.

[18]Zi Y, Ma C, He S, et al. Effects of intrauterine growth restriction during late pregnancy on the cell growth, proliferation, and differentiation in ovine fetal thymuses[J]. Anim Biosci, 2022, 35(7): 989-998. DOI:10.5713/ab.21.0414.

[19]Wu F, Tian F, Qin C, et al. Peroxiredoxin2 regulates trophoblast proliferation and migration through SPIB-HDAC2 pathway[J]. Exp Cell Res, 2023, 422(1): 113428. DOI:10.1016/j.yexcr.2022.113428.

[20]Li Y, Qin W, Liang Q, et al. Bufei huoxue capsule alleviates bleomycin-induced pulmonary fibrosis in mice via TGF-beta1/Smad2/3 signaling[J]. J Ethnopharmacol, 2023, 316: 116733. DOI:10.1016/j.jep.2023.116733.

[21]Zhao Y, Guo C, Zeng L, et al. Mesenchymal stem cells ameliorate fibrosis by enhancing autophagy via inhibiting Galectin-3/Akt/mTOR pathway and by alleviating the EMT via inhibiting Galectin-3/Akt/GSK3β/Snail pathway in NRK-52E fibrosis[J]. Int J Stem Cells, 2023, 16(1): 52-65. DOI:10.15283/ijsc22014.

[22]Tong KK, Ma TC, Kwan KM. BMP/Smad signaling and embryonic cerebellum development: stem cell specification and heterogeneity of anterior rhombic lip[J]. Dev Growth Differ, 2015, 57(2):121-134. DOI: 10.1111/dgd.12198.

[23]Li F, Tang H, Zhao S, et al. Circ-E-Cad encodes a protein that promotes the proliferation and migration of gastric cancer via the TGF-beta/Smad/C-E-Cad/PI3K/AKT pathway[J]. Mol Carcinog, 2023, 62(3): 360-368. DOI:10.1002/mc.23491.

[24]Wang H, Liang W, Wang X, et al. Notch mediates the glycolytic switch via PI3K/Akt signaling to support embryonic development[J].Cell Mol Biol Lett, 2023, 28(1): 50. DOI: 10.1186/s11658-023-00459-4.

[25]Xiong X, Yang M, Hai Z, et al. Maternal Kdm2a-mediated PI3K/Akt signaling and E-cadherin stimulate the morula-to-blastocyst transition revealing crucial roles in early embryonic development[J]. Theriogenology, 2023, 209: 60-75. DOI: 10.1016/j.theriogenology.2023.06.017.

[26]Chen X, Song QL, Wang JY, et al. FKBP5 regulates trophoblast-macrophage crosstalk in recurrent spontaneous abortion through PI3K/AKT and NF-kappaB signaling pathways[J]. Free Radic Biol Med, 2023, 209(Pt 1): 55-69. DOI: 10.1016/j.freeradbiomed.2023.10.380.

基于TGF-β1和E-Cad表达调控及相关信号通路探讨胚胎停育的发生机制

Exploration on mechanism of embryo damage based on TGF-β1, E-Cad, and related signaling pathways

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 2

编辑推荐

Metrics

[1]	阎红卫屈萍贾青鸽殷婷. 染色体微阵列分析胚胎停育中的遗传学因素及预测模型建立 [J]. 国际医药卫生导报, 2025, 31(14): 2299-2304.
[2]	鲁旭赵英娟李丹青. HMGB1、PCT、TGF-β1水平与新生儿重症肺炎病情相关性及对预后的影响 [J]. 国际医药卫生导报, 2024, 30(22): 3712-3717.