Acknowledgement
This work was supported by grants from the National Nature Science Foundation (82104576), the Basic andApplied Basic Research Fund of Guangdong Province (2019A1515110579), the Scientific Research Project of Guangdong Bureau of Traditional Chinese Medicine (20201292), Shenzhen Science Technology and Innovation Committee (JCYJ20210324130012031 and JCYJ20210324130013033) and the Sanming Project of Medicine inShenzhen (SZSM201612046).
References
- RPL EGGo, Bender Atik R, Christiansen OB, Elson J, Kolte AM, Lewis S, et al. 2018. ESHRE guideline: recurrent pregnancy loss. Hum. Reprod. Open 2018: hoy004. https://doi.org/10.1093/hropen/hoy004
- de Moreuil C, Alavi Z, Pasquier E. 2020. Hydroxychloroquine may be beneficial in preeclampsia and recurrent miscarriage. Br. J. Clin. Pharmacol. 86: 39-49. https://doi.org/10.1111/bcp.14131
- Larsen EC, Christiansen OB, Kolte AM, Macklon N. 2013. New insights into mechanisms behind miscarriage. BMC Med. 11: 154. https://doi.org/10.1186/1741-7015-11-154
- Grande M, Borrell A, Garcia-Posada R, Borobio V, Munoz M, Creus M, et al. 2012. The effect of maternal age on chromosomal anomaly rate and spectrum in recurrent miscarriage. Hum. Reprod. 27: 3109-3117. https://doi.org/10.1093/humrep/des251
- Garrido-Gimenez C, Alijotas-Reig J. 2015. Recurrent miscarriage: causes, evaluation and management. Postgrad. Med. J. 91: 151-162. https://doi.org/10.1136/postgradmedj-2014-132672
- Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, et al. 2000. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13: 715-725. https://doi.org/10.1016/S1074-7613(00)00070-4
- Becker C, Wirtz S, Blessing M, Pirhonen J, Strand D, Bechthold O, et al. 2003. Constitutive p40 promoter activation and IL-23 production in the terminal ileum mediated by dendritic cells. J. Clin. Invest. 112: 693-706. https://doi.org/10.1172/JCI17464
- Tonel G, Conrad C, Laggner U, Di Meglio P, Grys K, McClanahan TK, et al. 2010. Cutting edge: A critical functional role for IL-23 in psoriasis. J. Immunol. 185: 5688-5691. https://doi.org/10.4049/jimmunol.1001538
- Teng MW, Bowman EP, McElwee JJ, Smyth MJ, Casanova JL, Cooper AM, et al. 2015. IL-12 and IL-23 cytokines: from discovery to targeted therapies for immune-mediated inflammatory diseases. Nat. Med. 21: 719-729. https://doi.org/10.1038/nm.3895
- Tang C, Chen S, Qian H, Huang W. 2012. Interleukin-23: as a drug target for autoimmune inflammatory diseases. Immunology 135: 112-124. https://doi.org/10.1111/j.1365-2567.2011.03522.x
- Li N, Wu HM, Hang F, Zhang YS, Li MJ. 2017. Women with recurrent spontaneous abortion have decreased 25(OH) vitamin D and VDR at the fetal-maternal interface. Braz. J. Med. Biol. Res. 50: e6527. https://doi.org/10.1590/1414-431x20176527
- Eaton LH, Dearman RJ, Kimber I, Griffiths CE. 2016. Interleukin-17 and interleukin-23 regulate Langerhans cell migration. Br. J. Dermatol. 175: 622-624. https://doi.org/10.1111/bjd.14541
- Coulthard LR, White DE, Jones DL, McDermott MF, Burchill SA. 2009. p38(MAPK): stress responses from molecular mechanisms to therapeutics. Trends Mol. Med. 15: 369-379. https://doi.org/10.1016/j.molmed.2009.06.005
- Arthur JS, Ley SC. 2013. Mitogen-activated protein kinases in innate immunity. Nat. Rev. Immunol. 13: 679-692. https://doi.org/10.1038/nri3495
- Yong HY, Koh MS, Moon A. 2009. The p38 MAPK inhibitors for the treatment of inflammatory diseases and cancer. Expert Opin. Investig. Drugs 18: 1893-1905. https://doi.org/10.1517/13543780903321490
- Ono K, Han J. 2000. The p38 signal transduction pathway: activation and function. Cell. Signal. 12: 1-13. https://doi.org/10.1016/S0898-6568(99)00071-6
- Yu L, Hebert MC, Zhang YE. 2002. TGF-beta receptor-activated p38 MAP kinase mediates smad-independent TGF-β responses. EMBO J. 21: 3749-3759. https://doi.org/10.1093/emboj/cdf366
- Seshadri S, Allan DSJ, Carlyle JR, Zenewicz LA. 2017. Bacillus anthracis lethal toxin negatively modulates ILC3 function through perturbation of IL-23-mediated MAPK signaling. PLoS Pathog. 13: e1006690. https://doi.org/10.1371/journal.ppat.1006690
- Gao P, Zha Y, Wei L, Zhou X, Zhu S, Zhang H, et al. 2022. G-CSF: A vehicle for communication between trophoblasts and macrophages which may cause problems in recurrent spontaneous abortion. Placenta 121: 164-172. https://doi.org/10.1016/j.placenta.2022.03.125
- Wu L, Cheng B, Liu Q, Jiang P, Yang J. 2020. CRY2 suppresses trophoblast migration and invasion in recurrent spontaneous abortion. J. Biochem. 167: 79-87. https://doi.org/10.1093/jb/mvz076
- Lamptey J, Li F, Adu-Gyamfi EA, Chen XM, Czika A, Otoo A, et al. 2021. Downregulation of fascin in the first trimester placental villi is associated with early recurrent miscarriage. Exp. Cell Res. 403: 112597. https://doi.org/10.1016/j.yexcr.2021.112597
- Gu Y, Xiao ZH, Wu J, Guo M, Lv P, Dou N. 2021. Anti-atherosclerotic effect of afrocyclamin A against vascular smooth muscle cells is mediated via p38 MAPK signaling pathway. Cell J. 23: 191-198.
- Guenther S, Vrekoussis T, Heublein S, Bayer B, Anz D, Knabl J, et al. 2012. Decidual macrophages are significantly increased in spontaneous miscarriages and over-express FasL: a potential role for macrophages in trophoblast apoptosis. Int. J. Mol. Sci. 13: 9069-9080. https://doi.org/10.3390/ijms13079069
- Red-Horse K, Zhou Y, Genbacev O, Prakobphol A, Foulk R, McMaster M, et al. 2004. Trophoblast differentiation during embryo implantation and formation of the maternal-fetal interface. J. Clin. Invest. 114: 744-754. https://doi.org/10.1172/JCI22991
- Li M, Zhang H, Kong Q. 2021. Long non-coding RNA IGF2-AS promotes trophoblast cell proliferation, migration, and invasion by regulating miR-520g/N-cadherin axis. J. Obstet. Gynaecol. Res. 47: 3047-3059. https://doi.org/10.1111/jog.14886
- Bulmer JN, Williams PJ, Lash GE. 2010. Immune cells in the placental bed. Int. J. Dev. Biol. 54: 281-294. https://doi.org/10.1387/ijdb.082763jb
- Zong S, Li C, Luo C, Zhao X, Liu C, Wang K, et al. 2016. Dysregulated expression of IDO may cause unexplained recurrent spontaneous abortion through suppression of trophoblast cell proliferation and migration. Sci. Rep. 6: 19916. https://doi.org/10.1038/srep19916
- Huang W, Lu W, Li Q, Zhang Y, Xie B, Luo S, et al. 2020. Effects of cyclosporine A on proliferation, invasion and migration of HTR-8/SVneo human extravillous trophoblasts. Biochem. Biophys. Res. Commun. 533: 645-650. https://doi.org/10.1016/j.bbrc.2020.09.072
- Li Z, Zhou G, Jiang L, Xiang H, Cao Y. 2018. Effect of STOX1 on recurrent spontaneous abortion by regulating trophoblast cell proliferation and migration via the PI3K/AKT signaling pathway. J. Cell. Biochem. 120: 8291-8299. https://doi.org/10.1002/jcb.28112
- Li S, Zhai J, Liu J, Hong Y, Zhao W, Zhao A, et al. 2017. BMAL1 facilitates trophoblast migration and invasion via SP1-DNMT1/DAB2IP pathway in recurrent spontaneous abortion. Oncotarget 8: 89451-89464. https://doi.org/10.18632/oncotarget.20702
- Liang H, Zhang Q, Lu J, Yang G, Tian N, Wang X, et al. 2016. MSX2 Induces trophoblast invasion in human placenta. PLoS One 11: e0153656. https://doi.org/10.1371/journal.pone.0153656
- Kalluri R, Weinberg RA. 2009. The basics of epithelial-mesenchymal transition. J. Clin. Invest. 119: 1420-1428. https://doi.org/10.1172/JCI39104
- Heerboth S, Housman G, Leary M, Longacre M, Byler S, Lapinska K, et al. 2015. EMT and tumor metastasis. Clin. Transl. Med. 4: 6. https://doi.org/10.1186/s40169-015-0048-3
- Lamouille S, Xu J, Derynck R. 2014. Molecular mechanisms of epithelial-mesenchymal transition. Nat. Rev. Mol. Cell Biol. 15: 178-196. https://doi.org/10.1038/nrm3758
- Zhang S, Ding J, Wang J, Yin T, Zhang Y, Yang J. 2021. CXCL5 Downregulation in villous tissue is correlated with recurrent spontaneous abortion. Front. Immunol. 12: 717483. https://doi.org/10.3389/fimmu.2021.717483
- Kim MS, Lee EJ, Kim HR, Moon A. 2003. p38 kinase is a key signaling molecule for H-Ras-induced cell motility and invasive phenotype in human breast epithelial cells. Cancer Res. 63: 5454-5461.
- Wang Z, Liu M, Nie X, Zhang Y, Chen Y, Zhu L, et al. 2015. NOD1 and NOD2 control the invasiveness of trophoblast cells via the MAPK/p38 signaling pathway in human first-trimester pregnancy. Placenta 36: 652-660. https://doi.org/10.1016/j.placenta.2015.03.004
- Zhao H, Li Y, Dong N, Zhang L, Chen X, Mao H, et al. 2021. LncRNA LINC01088 inhibits the function of trophoblast cells, activates the MAPK-signaling pathway and associates with recurrent pregnancy loss. Mol. Hum. Reprod. 27: gaab047. https://doi.org/10.1093/molehr/gaab047
- Underwood DC, Osborn RR, Kotzer CJ, Adams JL, Lee JC, Webb EF, et al. 2000. SB 239063, a potent p38 MAP kinase inhibitor, reduces inflammatory cytokine production, airways eosinophil infiltration, and persistence. J. Pharmacol. Exp. Ther. 293: 281-288.