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Research Article

Related genes and characteristic analysis of trophoblast cells during early embryo developmental cessation

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  • 1. Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China
    2. West China School of Basic Medical Sciences & Forensic Medicine, Chengdu 610041, China;
    3. Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China

Received date: 2020-08-08

  Revised date: 2020-10-02

  Online published: 2020-10-15

Supported by

Supported by the National Nature Science Foundation of China No(31771662);the National Science and Technology Major Project No(2018YFC1002803-3)

Abstract

Trophoblast cells play essential roles in the maintenance of normal embryo implantation, growth and development. The study of abnormal gene changes in trophoblastic cells from arrested embryos is helpful to understand the developmental mechanism of embryo developmental cessation or adverse pregnancy outcomes. In this study, we sequenced and analyzed the transcriptomes of the villi from ten women who have undergone abortion with either normal pregnancy or embryo development cessation. We found that there were 436 differentially expressed genes, of which 406 mRNA were significantly up-regulated and 32 mRNA were significantly down-regulated. Gene enrichment analysis showed that these genes were significantly enriched in immune-related functions and intercellular adhesion, such as lymphocyte activation, myeloid cell activation, extracellular matrix and collagen junction. And their potential regulatory pathways were enriched in terms of complement and coagulation cascade, extracellular matrix degradation. In addition, in this study the co-expression analysis of WGCNA was used to obtain the lncRNA with co-expression relationship with the differential genes. According to the different functions of the modules, two network diagrams were drawn, and four key genes were obtained, namely VSIG4, C1QC, CD36 and SPP1. These differential genes obtained in this study can be used as key molecules with potential effects on embryo development cessation. The enriched entries can provide a theoretical basis and new direction for further understanding of the etiology and mechanism of embryo development cessation or adverse pregnancy outcomes.

Cite this article

Yue Zhang, Ying Feng, Fang Ma . Related genes and characteristic analysis of trophoblast cells during early embryo developmental cessation[J]. Hereditas(Beijing), 2020 , 42(10) : 1004 -1016 . DOI: 10.16288/j.yczz.20-144

References

[1] Staud F, Karahoda R . Trophoblast: The central unit of fetal growth, protection and programming. Int J Biochem Cell Biol, 2018,105:35-40.
[2] Moser G, Windsperger K, Pollheimer J, de Sousa Lopes SC, Huppertz B,. Human trophoblast invasion: new and unexpected routes and functions. Histochem Cell Biol, 2018,150(4):361-370.
[3] Baines KJ, Renaud SJ . Transcription factors that regulate trophoblast development and function. Prog Mol Biol Transl Sci, 2017,145:39-88.
[4] Harris LK, Jones CJ, Aplin JD . Adhesion molecules in human trophoblast - a review. II. extravillous trophoblast. Placenta, 2009,30(4):299-304.
[5] Chung TW, Park MJ, Kim HS, Choi HJ, Ha KT . Integrin αVβ3 and αVβ5 are required for leukemia inhibitory factor-mediated the adhesion of trophoblast cells to the endometrial cells. Biochem Biophys Res Commun, 2016,469(4):936-940.
[6] Huppertz B . Traditional and new routes of trophoblast invasion and their implications for pregnancy diseases. Int J Mol Sci, 2019,21(1):289.
[7] Malik A, Pal R, Gupta SK . Interdependence of JAK-STAT and MAPK signaling pathways during EGF-mediated HTR-8/SVneo cell invasion. PLoS One, 2017,12(5):e0178269.
[8] Huang ZY, Li SW, Fan W, Ma QH . Transforming growth factor β1 promotes invasion of human JEG-3 trophoblast cells via TGF-β/Smad3 signaling pathway. Oncotarget, 2017,8(20):33560-33570.
[9] Chitu V, Stanley ER . Regulation of embryonic and postnatal development by the CSF-1 receptor. Curr Top Dev Biol, 2017,123:229-275.
[10] Ding JL, Yin TL, Yan NN, Cheng YX, Yang J . FasL on decidual macrophages mediates trophoblast apoptosis: A potential cause of recurrent miscarriage. Int J Mol Med, 2019,43(6):2376-2386.
[11] Shaik R, Ramakrishna W . Genes and Co-Expression modules common to drought and bacterial stress responses in arabidopsis and rice. PLoS One, 2013,8(10):e77261.
[12] Robinson MD, McCarthy DJ, Smyth GK,. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics, 2010,26(1):139-140.
[13] Takeshita A, Kusakabe KT, Hiyama M, Kuniyoshi N, Kondo T, Kano K, Kiso Y, Okada T . Dynamics and reproductive effects of complement factors in the spontaneous abortion model of CBA/J×DBA/2 mice. Immunobiology, 2014,219(5):385-391.
[14] Huang J, Qin H, Yang YH, Chen XY, Zhang JM, Laird S, Wang CC, Chan TF, Li TC . A comparison of transcriptomic profiles in endometrium during window of implantation between women with unexplained recurrent implantation failure and recurrent miscarriage. Reproduction, 2017,153(6):749-758.
[15] Yurdakan G, Ekem TE, Bahadir B, Gun BD, Kuzey GM, Ozdamar SO . Expression of adhesion molecules in first trimester spontaneous abortions and their role in abortion pathogenesis. Acta Obstet Gynecol Scand, 2008,87(7):775-782.
[16] Soylu Karap?nar O, Benk ?ilfeler D, Dolap??o?lu K, Keskin Kurt R, Beyaz?t A . The effect of molar pregnancies on platelet parameters. J Obstet Gynaecol, 2016,36(7):912-915.
[17] Girardi G, Salmon JB . The role of complement in pregnancy and fetal loss. Autoimmunity, 2003,36(1):19-26.
[18] Kouser L, Madhukaran SP, Shastri A, Saraon A, Ferluga J, Al-Mozaini M, Kishore U . Emerging and novel functions of complement protein C1q. Front Immunol, 2015,6:317.
[19] Liu FL, Zhou J, Zhang W, Wang H . Epigenetic regulation and related diseases during placental development. Hereditas (Beijing), 2017,39(4):263-275.
[19] 刘福林, 周瑾, 张蔚, 汪晖 . 胎盘发育过程中的表观遗传学改变及其相关疾病. 遗传, 2017,39(4):263-275.
[20] Lai XM, Wang YX . Trophoblastic invasion and its regulatory factors. Chin J Birth Heal Hered, 2007,15(3):1-3.
[20] 赖雪梅, 王应雄 . 滋养层侵袭力及其调控因素. 中国优生与遗传杂志, 2007,15(3):1-3.
[21] Burton GJ, Jauniaux E . Pathophysiology of placental- derived fetal growth restriction. Am J Obstet Gynecol, 2018,218(2S):S745-S761.
[22] James-Allan LB, Whitley GS, Leslie K, Wallace A, Cartwright JE . Decidual cell regulation of trophoblast is altered in pregnancies at risk of pre-eclampsia. J Mol Endocrinol, 2018.
[23] Zadrozna M, Nowak B, Marcinek A, Duc J . Villous trophoblast cell turnover in placentas from preterm pregnancy and pregnancy complicated by intrauterine growth restriction (IUGR). Folia Biol (Krakow), 2009,58(1-2):79-83.
[24] Check JH, Aly J, Chang E . Improving the chance of successful implantation-Part I-Embryo attachment to the endometrium and adequate trophoblast invasion. Clin Exp Obstet Gynecol, 2016,43(6):787-791.
[25] Burton GJ, Jauniaux E . The cytotrophoblastic shell and complications of pregnancy. Placenta, 2017,60:134-139.
[26] Yang WM, Lu ZY, Zhi ZF, Liu LL, Deng LJ, Jiang XL, Pang LH . High-throughput transcriptome-Seq and small RNA-Seq reveal novel functional genes and microRNAs for early embryonic arrest in humans. Gene, 2019,697:19-25.
[27] Pan HT, Ding HG, Fang M, Yu B, Cheng Y, Tan YJ, Fu QQ, Lu BB, Cai HG, Jin X, Xia XQ, Zhang T . Proteomics and bioinformatics analysis of altered protein expression in the placental villous tissue from early recurrent miscarriage patients. Placenta, 2018,61:1-10.
[28] Atanasova MA, Konova EI, Aleksovska TA, Todorova KN, Georgieva MN, Lukanov TH . Anti-fibrillin-1 autoantibodies in normal pregnancy and recurrent pregnancy loss. Autoimmun Rev, 2011,10(3):131-136.
[29] Vogt L, Schmitz N, Kurrer MO, Bauer M, Hinton HI, Behnke S, Gatto D, Sebbel P, Beerli RR, Sonderegger I, Kopf M, Saudan P, Bachmann MF . VSIG4, a B7 family-related protein, is a negative regulator of T cell activation. J Clin Invest, 2006,116(10):2817-2826.
[30] Helmy KY, Katschke KJ, Gorgani NN, Kljavin NM, Elliott JM, Diehl L, Scales SJ, Ghilardi N, van Lookeren Campagne M,. CRIg: A macrophage complement receptor required for phagocytosis of circulating pathogens. Cell, 2006,124(5):915-927.
[31] Kim DD, Miwa T, Kimura Y, Schwendener RA, van Lookeren Campagne M, Song WC,. Deficiency of decay- accelerating factor and complement receptor 1-related gene/protein y on murine platelets leads to complement- dependent clearance by the macrophage phagocytic receptor CRIg. Blood, 2008,112(4):1109-1119.
[32] Mascarell L, Airouche S, Berjont N, Gary C, Gueguen C, Fourcad G, Bellier B, Togbe D, Ryffel B, Klatzmann D, Baron-Bodo V, Moingeon P . The regulatory dendritic cell marker C1q is a potent inhibitor of allergic inflammation. Mucosal Immunol, 2016,10(3):695-704.
[33] Girardi G . Complement inhibition keeps mothers calm and avoids fetal rejection. Immunol Invest, 2008,37(5):645-659.
[34] Girardi G, Prohászka Z, Bulla R, Tedesco F, Scherjon S . Complement activation in animal and human pregnancies as a model for immunological recognition. Mol Immunol, 2011,48(14):1621-1630
[35] Teiril? L, Heikkinen-Eloranta J, Kotimaa J, Meri S, Lokki AI . Regulation of the complement system and immunological tolerance in pregnancy. Semin Immunol, 2019,45:101337.
[36] Sun J, Jin L . Trophinin, tastin, bystin complex binds to embryo initiation. Chin J Birth Heal Hered, 2005,13(5):113-114.
[36] 孙虹, 靳镭 . Trophinin, tastin, bystin复合体与胚胎起始黏附. 中国优生与遗传杂志, 2005,13(5):113-114.
[37] Oz HS, Ebersole JL, de Villiers WJS,. The macrophage pattern recognition scavenger receptors SR-A and CD36 protect against microbial induced pregnancy loss. Inflamm Res, 2011,60(1):93-97.
[38] Silverstein RL, Febbraio M . CD36, a scavenger receptor involved in immunity, metabolism, angiogenesis, behavior. SciSignal, 2009, 2(72): re3.
[39] Abumrad NA, Goldberg IJ . CD36 actions in the heart: Lipids, calcium, inflammation, repair and more? Biochim Biophys Acta, 2016,1861(10):1442-1449.
[40] Wang JC, Li YS . CD36 tango in cancer: signaling pathways and functions. Theranostics, 2019,9(17):4893-4908.
[41] Johnson GA, Burghardt RC, Bazer FW, Spencer TE . Osteopontin: Roles in implantation and placentation. Biol Reprod, 2003,69(5):1458-1471.
[42] Yu QB, Wang YX . Cell adhesion molecules to the embryo implantatio. Chin J Birth Heal Hered, 2005,13(1):6-8.
[42] 余秋波, 王应雄 . 细胞粘附分子与胚胎着床. 中国优生与遗传杂志, 2005,13(1):6-8.
[43] Nardo LG, Nikas G, Makrigiannakis A . Molecules in blastocyst implantation. Role of matrix metalloproteinases, cytokines and growth factors. J Reprod Med, 2003,48(3):137-147.
[44] Gonzalez I, Munita R, Agirre E, Dittmer TA, Gysling K, Misteli T, Luco RF . A lncRNA regulates alternative splicing via establishment of a splicing-specific chromatin signature . Nat Struct Mol Biol, 2015,22(5):370-376.
[45] Lieberman J . Tapping the RNA world for therapeutics. Nat Struct Mol Biol, 2018,25(5):357-364.
[46] Pérez-Palacios R, Fauque P, Teissandier A, Bourc'his D. Deciphering the early mouse embryo transcriptome by Low-Input RNA-Seq. Methods Mol Biol, 2021,2214:189-205.
[47] Svensson V, Natarajan KN, Ly LH, Miragaia RJ, Labalette C, Macaulay IC, Cvejic A, Teichmann SA . Power analysis of single-cell RNA-sequencing experiments. Nat Methods, 2017,14(4):381-387.
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