The Signaling Pathways Involved in Embryo Implantation

doi:10.12280/gjszjk.20220074

Abstract

Abstract:

Embryo implantation and fetal development are the process of mutual recognition and adaptation of mother and fetus. The molecular mechanisms of this process are complex. However, the exact mechanisms have not yet been elucidated. Implantation failure is one of the important causes of unexplained infertility, early miscarriage and repeated implantation failure. Embryo implantation is closely related to endometrial receptivity, and various cytokines secreted during implantation can regulate endometrial receptivity and effectively improve pregnancy outcomes. Current studies have found that the Notch, Janus kinase-signal transducer and activator of transcription, Wnt/β-catenin, mitogen activated protein kinase, nuclear factor κB and other signals are involved in embryo implantation. We review the research progress of the signaling pathways involved in embryo implantation, as a reference for exploring the mechanism of embryo implantation and improving pregnancy outcome.

Key words: Embryo implantation, Signal transduction, Janus kinases, Wnt signaling pathway, MAP kinase signaling system, NF-kappa B, Endometrial receptivity, Notch, Signal transduction and activator of transcription

ZHU Xia, LI Hui-zhen, LIU Dan, MA Tian-zhong. The Signaling Pathways Involved in Embryo Implantation[J]. Journal of International Reproductive Health/Family Planning, 2022, 41(5): 409-413.

References 33

[1]	Sehring J, Beltsos A, Jeelani R. Human implantation: The complex interplay between endometrial receptivity, inflammation, and the microbiome[J]. Placenta, 2022, 117:179-186. doi: 10.1016/j.placenta.2021.12.015. doi: 10.1016/j.placenta.2021.12.015 URL
[2]	Massimiani M, Lacconi V, La Civita F, et al. Molecular Signaling Regulating Endometrium-Blastocyst Crosstalk[J]. Int J Mol Sci, 2019, 21(1):23. doi: 10.3390/ijms21010023. doi: 10.3390/ijms21010023 URL
[3]	Moldovan GE, Miele L, Fazleabas AT. Notch signaling in reproduction[J]. Trends Endocrinol Metab, 2021, 32(12):1044-1057. doi: 10.1016/j.tem.2021.08.002. doi: 10.1016/j.tem.2021.08.002 URL
[4]	Afshar Y, Miele L, Fazleabas AT. Notch1 is regulated by chorionic gonadotropin and progesterone in endometrial stromal cells and modulates decidualization in primates[J]. Endocrinology, 2012, 153(6):2884-2896. doi: 10.1210/en.2011-2122. doi: 10.1210/en.2011-2122 pmid: 22535768
[5]	Afshar Y, Jeong JW, Roqueiro D, et al. Notch1 mediates uterine stromal differentiation and is critical for complete decidualization in the mouse[J]. FASEB J, 2012, 26(1):282-294. doi: 10.1096/fj.11-184663. doi: 10.1096/fj.11-184663 pmid: 21990372
[6]	Wu Y, He JP, Xie J, et al. Notch1 is crucial for decidualization and maintaining the first pregnancy in the mouse[J]. Biol Reprod, 2021, 104(3):539-547. doi: 10.1093/biolre/ioaa222. doi: 10.1093/biolre/ioaa222 URL
[7]	Bao H, Sun Y, Yang N, et al. Uterine Notch2 facilitates pregnancy recognition and corpus luteum maintenance via upregulating decidual Prl8a2[J]. PLoS Genet, 2021, 17(8):e1009786. doi: 10.1371/journal.pgen.1009786. doi: 10.1371/journal.pgen.1009786 URL
[8]	Zhou W, Menkhorst E, Dimitriadis E. Jagged1 regulates endometrial receptivity in both humans and mice[J]. FASEB J, 2021, 35(8):e21784. doi: 10.1096/fj.202100590R. doi: 10.1096/fj.202100590R
[9]	Marchetto NM, Begum S, Wu T, et al. Endothelial Jagged1 Antagonizes Dll4/Notch Signaling in Decidual Angiogenesis during Early Mouse Pregnancy[J]. Int J Mol Sci, 2020, 21(18):6477. doi: 10.3390/ijms21186477. doi: 10.3390/ijms21186477 URL
[10]	Jiang Y, Yuan X, Li B, et al. TOB1 modulates the decidualization of human endometrial stromal cells via the Notch pathway[J]. J Assist Reprod Genet, 2021, 38(10):2641-2650. doi: 10.1007/s10815-021-02277-z. doi: 10.1007/s10815-021-02277-z URL
[11]	Batista MR, Diniz P, Torres A, et al. Notch signaling in mouse blastocyst development and hatching[J]. BMC Dev Biol, 2020, 20(1):9. doi: 10.1186/s12861-020-00216-2. doi: 10.1186/s12861-020-00216-2 pmid: 32482162
[12]	Hu X, Li J, Fu M, et al. The JAK/STAT signaling pathway: from bench to clinic[J]. Signal Transduct Target Ther, 2021, 6(1):402. doi: 10.1038/s41392-021-00791-1. doi: 10.1038/s41392-021-00791-1 URL
[13]	Feng Q, Gao B, Huang H, et al. Growth hormone promotes human endometrial glandular cells proliferation and motion through the GHR-STAT3/5 pathway[J]. Ann Transl Med, 2020, 8(4):53. doi: 10.21037/atm.2019.12.08. doi: 10.21037/atm.2019.12.08 pmid: 32175347
[14]	Zhou C, Lv M, Wang P, et al. Sequential activation of uterine epithelial IGF1R by stromal IGF1 and embryonic IGF2 directs normal uterine preparation for embryo implantation[J]. J Mol Cell Biol, 2021, 13(9):646-661. doi: 10.1093/jmcb/mjab034. doi: 10.1093/jmcb/mjab034 pmid: 34097060
[15]	Mrozikiewicz AE, Oż arowski M, Jędrzejczak P. Biomolecular Markers of Recurrent Implantation Failure-A Review[J]. Int J Mol Sci, 2021, 22(18):10082. doi: 10.3390/ijms221810082. doi: 10.3390/ijms221810082 URL
[16]	Fukui Y, Hirota Y, Saito-Fujita T, et al. Uterine Epithelial LIF Receptors Contribute to Implantation Chamber Formation in Blastocyst Attachment[J]. Endocrinology, 2021, 162(11):bqab169. doi: 10.1210/endocr/bqab169. doi: 10.1210/endocr/bqab169 URL
[17]	Hamelin-Morrissette J, Dallagi A, Girouard J, et al. Leukemia inhibitory factor regulates the activation of inflammatory signals in macrophages and trophoblast cells[J]. Mol Immunol, 2020, 120:32-42. doi: 10.1016/j.molimm.2020.01.021. doi: S0161-5890(19)30602-9 pmid: 32045772
[18]	Liu J, Xiao Q, Xiao J, et al. Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities[J]. Signal Transduct Target Ther, 2022, 7(1):3. doi: 10.1038/s41392-021-00762-6. doi: 10.1038/s41392-021-00762-6 URL
[19]	Sidrat T, Rehman ZU, Joo MD, et al. Wnt/β-catenin Pathway-Mediated PPARδ Expression during Embryonic Development Differentiation and Disease[J]. Int J Mol Sci, 2021, 22(4):1854. doi: 10.3390/ijms22041854. doi: 10.3390/ijms22041854
[20]	Chen Q, Ni Y, Han M, et al. Integrin-linked kinase improves uterine receptivity formation by activating Wnt/β-catenin signaling and up-regulating MMP-3/9 expression[J]. Am J Transl Res, 2020, 12(6):3011-3022. pmid: 32655826
[21]	Zhang FL, Huang YL, Zhou XY, et al. Telocytes enhanced in vitro decidualization and mesenchymal-epithelial transition in endometrial stromal cells via Wnt/β-catenin signaling pathway[J]. Am J Transl Res, 2020, 12(8):4384-4396.
[22]	Oghbaei F, Zarezadeh R, Jafari-Gharabaghlou D, et al. Epithelial-mesenchymal transition process during embryo implantation[J]. Cell Tissue Res, 2022, 388(1):1-17. doi: 10.1007/s00441-021-03574-w. doi: 10.1007/s00441-021-03574-w URL
[23]	Li Q, Shi J, Liu W. The role of Wnt/β-catenin-lin28a/let-7 axis in embryo implantation competency and epithelial-mesenchymal transition (EMT)[J]. Cell Commun Signal, 2020, 18(1):108. doi: 10.1186/s12964-020-00562-5. doi: 10.1186/s12964-020-00562-5 pmid: 32650795
[24]	Guo YJ, Pan WW, Liu SB, et al. ERK/MAPK signalling pathway and tumorigenesis[J]. Exp Ther Med, 2020, 19(3):1997-2007. doi: 10.3892/etm.2020.8454. doi: 10.3892/etm.2020.8454
[25]	马铭艳, 杨美霞, 韩晓敏, 等. MAPK信号通路在自然流产中机制研究进展[J]. 中国计划生育学杂志, 2020, 28(9):1504-1508. doi: 10.3969/j.issn.1004-8189.2020.09.043. doi: 10.3969/j.issn.1004-8189.2020.09.043
[26]	Goryszewska-Szczurek E, Baryla M, Kaczynski P, et al. Prokineticin 1-prokineticin receptor 1 signaling in trophoblast promotes embryo implantation and placenta development[J]. Sci Rep, 2021, 11(1):13715. doi: 10.1038/s41598-021-93102-1. doi: 10.1038/s41598-021-93102-1 pmid: 34215801
[27]	胡世福, 夏伟, 朱长虹. P38αMAPK在雌性生殖系统中的研究进展[J]. 国际生殖健康/计划生育杂志, 2015, 34(1):64-68.
[28]	Williams LM, Gilmore TD. Looking Down on NF-κB[J]. Mol Cell Biol, 2020, 40(15):e00104-20. doi: 10.1128/MCB.00104-20. doi: 10.1128/MCB.00104-20
[29]	Zhu C, Hu W, Zhao M, et al. The Pre-Implantation Embryo Induces Uterine Inflammatory Reaction in Mice[J]. Reprod Sci, 2021, 28(1):60-68. doi: 10.1007/s43032-020-00259-7. doi: 10.1007/s43032-020-00259-7 URL
[30]	Sakowicz A. The role of NFκB in the three stages of pregnancy - implantation, maintenance, and labour: a review article[J]. BJOG, 2018, 125(11):1379-1387. doi: 10.1111/1471-0528.15172. doi: 10.1111/1471-0528.15172 URL
[31]	Zhang Q, Lenardo MJ, Baltimore D. 30 Years of NF-κB: A Blossoming of Relevance to Human Pathobiology[J]. Cell, 2017, 168(1/2):37-57. doi: 10.1016/j.cell.2016.12.012. doi: 10.1016/j.cell.2016.12.012 URL
[32]	Ersahin A, Acet M, Acet T, et al. Disturbed endometrial NF-κB expression in women with recurrent implantation failure[J]. Eur Rev Med Pharmacol Sci, 2016, 20(24):5037-5040.
[33]	Feng R, Qin X, Li Q, et al. Progesterone regulates inflammation and receptivity of cells via the NF-κB and LIF/STAT3 pathways[J]. Theriogenology, 2022, 186:50-59. doi: 10.1016/j.theriogenology.2022.04.005. doi: 10.1016/j.theriogenology.2022.04.005 pmid: 35430548