Wnt信号通路在牛胎盘发育过程中的功能研究进展

doi:10.16431/j.cnki.1671-7236.2017.01.022

摘要/Abstract

摘要：

胎盘是哺乳动物在妊娠期间胎儿和母体之间的联系枢纽，因此，胎盘发育是否正常在妊娠中起着关键的作用。Wnt信号通路在胚胎发育和胎盘形成的过程中有着重要的作用，作者通过回顾几条已经研究较为清楚的Wnt信号通路和牛早期胚胎和胎盘的形成过程，介绍了Wnt信号通路的组成部分在体细胞核移植（somatic cell nuclear transfer，SCNT）牛和正常人工授精的牛的胚胎早期表达，提出了DKK-1和Fzd4的表达对于早期胎盘形成和发育有特殊的作用。此外，抑制MAP2K和GSK3信号可以激活Wnt信号通路，增加内细胞团和滋养层细胞的数量，加速囊胚的发育。SCNT牛和正常人工授精的牛早期胎盘中E-cadherin和β-catenin蛋白的磷酸化程度相似，所以对于Wnt信号通路在牛胎盘的早期形成和发育中的作用还需进一步的了解和研究。

关键词: 牛; 胎盘; Wnt信号通路

Abstract:

Placenta is the link between the fetus and the maternal body during pregnancy.Therefore, the pregnancy outcome of the key was related by the normal development of the placenta.Wnt signaling pathway plays an important role in the development of embryo and placenta formation, several Wnt pathways which have been clear study and the formation process of early embryo and placenta in cattle are reviewed in this article,the early expression of the Wnt pathway components in the somatic cell nuclear transfer (SCNT) cattle and normal insemination of bovine embryos is introduced. The expression of DKK-1 and Fzd4 have a special role in the formation and development of early placenta, but its molecular mechanism is not clear. In addition, the Wnt signaling pathway is activated by inhibiting the MAP2K and GSK3, led to the inner cell mass and trophoblast cell number increased and blastocyst development speed. But it is similar to the extent of phosphorylation of E-cadherin and beta-catenin protein in the early placenta of cows with SCNT and normal insemination, therefore, the role of Wnt signaling pathway in the early formation and development of bovine placenta should be further understood and studied.

Key words: bovine; placenta; Wnt signaling pathway

中图分类号:

S814.6

孙宏亮, 许美花, 王瑶, 鲁文赓. Wnt信号通路在牛胎盘发育过程中的功能研究进展[J]. 《中国畜牧兽医》, 2017, 44(1): 161-166.

SUN Hong-liang, XU Mei-hua, WANG Yao, LU Wen-geng. Research Progress on the Function of Wnt Signaling Pathway in the Development of Bovine Placenta[J]. , 2017, 44(1): 161-166.

参考文献

[1] 刘丑生, 李魁.胚胎移植技术在养牛生产中的应用研究[J].甘肃畜牧兽医,2000, 151(2):39-41.
[2] 石国庆. 动物胚胎移植与胚胎分割技术研究进展[J].黑龙江动物繁殖, 1999, 7(2):37-41.
[3] 朱玉林, 赵俊金, 赵小丽.牛胚胎移植的发展概况[J].农牧产品开发, 2001, 3:21-22.
[4] Cibelli J B, Campbell K H, Seidel G E, et al. The health profile of cloned animals[J]. Nat Biotechnol,2002,20(1):13-14.
[5] Permington K A,Schlitt J M,Jackson D L, et al. Preeclampsia:Multiple approaches for amultifactorial disease[J].Dis Model Mech, 2012, 5(1):9-18.
[6] Zhou Y, Fisher S J,Janatpour M, et al. Human cytotrophoblasts adopt a vascular phenotypeas they differentiate.A strategy for successful endovascular invasion[J].J Clin Invest,1997,99(9):2139-2151.
[7] 苏尚,吴畏. Wnt/β-catenin信号通路对靶基因转录的调控[J]. 中国科学,2014, 44(10):1029-1042.
[8] Holstein T W. The evolution of the Wnt pathway[J]. Cold Spring Harb Perspect Biol, 2012, 4(7):a007922.
[9] Niehrs C.The complex world of Wnt receptor signaling[J]. Nat Rev Mol Cell Biol,2012,13(12):767-779.
[10] Roberts D J,Post M D.The placenta in pre-eclampsia and intrauterine growth restriction[J]. J Clin Pathol, 2008, 61(12):1254-1260.
[11] Aisagbonhi O, Rai M, Ryzhov S, et al. Experimental myocardial infarction triggers canonical Wnt signaling and endothelial-to-mesenchymal transition[J]. DisModel Mech, 2011, 4(4):469-483.
[12] Poon R, Hong H, Wei X, et al. A high throughput screen identifies Nefopamas targeting cell proliferation in β-catenin driven neoplastic and reactive fibroproliferative disorders[J]. PLoS One, 2012, 7(5):e37940.
[13] Huelsken J, Birchmeier W. New aspects of Wnt signaling pathways in higher vertebrates[J].Curr Opin Genet Dev, 2011,11(5):547-553.
[14] 施剑明,邬亚华,耿书国,等. 间充质干细胞增殖、衰老及分化:Wnt信号通路经典与非经典的调控作用[J]. 中国组织工程研究, 2014, 18(41):6719-6724.
[15] Teo J L, Kahn M. The Wnt signaling pathway in cellular proliferation and differentiation:A tale of two coactivators[J].Adv Drug Deliv Rev, 2010, 62(12):1149-1155.
[16] Clevers H, Nusse R. Wnt/β-catenin signaling and disease[J].Cell, 2012, 149(6):1192-1205.
[17] Caraci F, Busceti C, Biagioni F,et al.The Wnt antagonist,Dickkopf-1, as a target for the treatment of neuro degenerative disorders[J].Neurochem Res, 2008, 33(12):2401-2406.
[18] Chilov D, Sinjushina N,Rita H, et al.Phosphorylated beta-catenin localizes to centrosomes of neuronal progenitors and is required for cell polarity and neurogenesis in developing midbrain[J]. Developmental Biology, 2011, 357(1):259-268.
[19] Bahmanyar S, Kaplan D D, Deluca J G, et al. beta-Catenin is a Nek2 substrate involved in centrosome separation[J].Genes & Development, 2008, 22(1):91-105.
[20] Fumoto K, Hoogenraad C C, Kikuchi A. GSK-3beta-regulated interaction of BICD with dynein is involved in microtubule anchorage at centrosome[J].EMBO J, 2006, 25(24):5670-5682.
[21] Acevedo N, Wang X, Dunn R L, et al. Glycogen synthase kinase-3 regulation of chromatin segregation and cytokinesis in mouse preimplantation embryos[J]. Mol Reprod Dev, 2007, 74(2):178-188.
[22] Hadjihannas M V, Bruckner M, Behrens J, et a1. Conductin/axin2 and Wnt signaling regulates centrosome cohesion[J]. EMBO Rep, 2010, 11(4):317-324.
[23] Mbom B C, Siemers K A, Ostrowski M A, et al.Nek2 phosphorylates and stabilizes β-catenin at mitotic centrosomes ownstream of Plk1[J].Mol Biol Cell, 2014, 25(7):977-991.
[24] 孟道林, 何跃君, 徐海, 等.结肠癌组织Wnt/PCP信号通路相关因子表达及其意义[J].中国肿瘤外科杂志, 2016, 8(1):19-22.
[25] 胡成龙,孙洁文, 侯烨,等.Wnt信号通路在造血干细胞自我更新和扩增中的作用[J].中国细胞生物学学报, 2014, 36(11):1532-1542.
[26] Nishita M, Itsukushima S, Nomachi A, et al. Ror2/Frizzled complex mediates Wnt5a-induced AP-1 activation by regulating dishevelled polymerization[J].Mol Cell Biol, 2010, 30(14):3610-3619.
[27] Gebruers E, Cordero-Maldonado M L, Gray A I, et al. Aphenotypic screen in zebrafish identifyes a novel small-molecule inducer of ectopic tail formation suggestive of alterations in non-canonical Wnt/PCP signaling[J].PLoS One,2013, 8(12):e83293.
[28] De A. Wnt/Ca²⁺ signaling pathway:A brief overview[J].Acta Biochim Biophys Sin (Shanghai), 2011, 43(10):745-756.
[29] Sassi N, Laadhar L, Allouche M, et al.Wnt signaling and chondrocytes:From cell fate determination to osteoarthritis physiopathology[J].J Recept Signal Transduct Res, 2014, 34(2):73-80.
[30] Kim J, Kim D W, Chang W, et al. Wnt5a is secreted by follicular dendritic cells to protect germinal center B cells via Wnt/Ca²⁺/NFAT/NF-κB-B cell lymphoma 6 signaling[J].J Immunol, 2012, 188(1):182-189.
[31] 刘娜, 李华, 张洋, 等.炎症微环境作用下非经典Wnt/Ca²⁺ 信号通路对牙周膜干细胞成骨分化的影响[J].中华老年口腔医学杂志, 2015, 13(5):257-262.
[32] 杨利国.动物繁殖学[M]. 北京.中国农业出版社,2003.
[33] 李瑞梅, 陈秀荔,靳亚平. 胚胎植入及其分子机制研究进展[J]. 动物医学进展, 2006, 27(4):22-25.
[34] 甘潇, 侯蓉, 张明,等.哺乳动物滋养层细胞在胚胎植入中的作用[J].四川动物, 2005, 24(4):660-664.
[35] 姜怀志,李金艳,马宁,等. 反刍动物的胚胎着床与妊娠识别过程的研究进展[J].吉林农业大学学报, 2003,25(5):578-582.
[36] 吕芳,王丽丽,贺斌,等. 胎盘发育及功能评价的研究进展[J]. 生殖医学杂志, 2012, 21(1):73-76.
[37] 敖政,刘德武,蔡更元,等. 克隆哺乳动物的胎盘发育缺陷[J]. 遗传, 2016, 38(5):402-410.
[38] 张玉玲,夏银可,靳丽军,等.micro与胎盘发育关系的研究进展[J]. 中国畜牧兽医, 2011, 38(8):43-47.
[39] Rena V, Flores-Martín J, Angeletti S, et al. StarD7 gene expression in trophoblast cells:Contribution of SF-1 and Wnt-β-catenin signaling[J]. Mol Endocrinol, 2011, 25(8):1364-1375.
[40] Kohan-Ghadr H R, Smith L C, Arnold D R, et al. Aberrant expression of E-cadherin and beta-catenin proteins in placenta of bovine embryos derived from somatic cell nuclear transfer[J].Reprod Fertil Dev, 2012, 24(4):588-598.
[41] Lu W, Tu Z, Wang S, et al. Spatiotemporal expression of Wnt signaling pathway components during bovine placental development[J]. Theriogenology, 2013, 80(8):893-902.
[42] Ye X, Wang Y, Cahill H, et al. Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization[J]. Cell, 2009, 139(2):285-298.
[43] Ledgard A, Lee R S, Couldrey C, et al. Dickkopf-1 expression during early bovine placentation and its down-regulation in somatic cell nuclear transfer (SCNT) pregnancies[J]. J Reprod Dev, 2009, 55(5):467-474.
[44] Daina H, Huang B, Oback B. Inhibition of MAP2K and GSK3 signaling promotes bovine blastocyst development and epiblast-associated expression of pluripotency factors[J].Biol Reprod, 2013, 88(3):74-84.
[45] McLean Z, Meng F, Henderson H, et al. Increased MAP kinase inhibition enhances epiblast-specific gene expression in bovine blastocysts[J].Biol Reprod, 2014, 91(2):49-59.