
国际妇产科学杂志 ›› 2023, Vol. 50 ›› Issue (4): 409-415.doi: 10.12280/gjfckx.20230007
收稿日期:2023-01-04
出版日期:2023-08-15
发布日期:2023-08-15
通讯作者:
陈凌,E-mail: 基金资助:
LIU Bing-bing, XU Yan-ning, CHEN Ling△(
)
Received:2023-01-04
Published:2023-08-15
Online:2023-08-15
摘要:
胚胎停育是指因受精卵缺陷或母体存在不利于妊娠因素而导致妊娠早期胚胎死亡而停止继续发育的现象,是一种常见的早期病理性妊娠。其发病率逐年增加,已成为最常见的妊娠并发症,最终可导致自然流产、稽留流产的发生。胚胎停育发生与许多因素有关,其中约半数与免疫因素有关。细胞因子是一类能调节免疫反应的生物活性分子,其中与炎症有关的称为炎症细胞因子。子宫蜕膜、滋养层细胞可以分泌多种炎症细胞因子。近年研究表明,在胚胎发育过程中多种炎症细胞因子之间相互协同、依赖又相互拮抗构成细胞因子网络,参与母胎界面免疫应答,使其导致胚胎停育的确切机制及信号通路错综复杂。综述炎症细胞因子与胚胎停育的关系及相关机制,以期为胚胎停育的预防和开发靶向治疗药物奠定理论基础。
刘冰冰, 徐燕宁, 陈凌. 炎症细胞因子与胚胎停育的关系[J]. 国际妇产科学杂志, 2023, 50(4): 409-415.
LIU Bing-bing, XU Yan-ning, CHEN Ling. The Relationship between Inflammatory Cytokines and Embryo Arrest[J]. Journal of International Obstetrics and Gynecology, 2023, 50(4): 409-415.
| [1] |
季玉琴, 张玉泉. 胚胎停止发育病因与机制的研究进展[J]. 现代妇产科进展, 2010, 19(2):146-148. doi: 10.13283/j.cnki.xdfckjz.2010.02.014.
doi: 10.13283/j.cnki.xdfckjz.2010.02.014 |
| [2] |
Schummers L, Oveisi N, Ohtsuka MS, et al. Early pregnancy loss incidence in high-income settings: a protocol for a systematic review and meta-analysis[J]. Syst Rev, 2021, 10(1):274. doi: 10.1186/s13643-021-01815-1.
doi: 10.1186/s13643-021-01815-1 pmid: 34696805 |
| [3] |
Liu H, Lin XX, Huang XB, et al. Systemic Characterization of Novel Immune Cell Phenotypes in Recurrent Pregnancy Loss[J]. Front Immunol, 2021, 12:657552. doi: 10.3389/fimmu.2021.657552.
doi: 10.3389/fimmu.2021.657552 |
| [4] |
Herkiloglu D, Gokce S, Cevik O. Relationship of interferon regulator factor 5 and interferon-urrent Pregnancy Loss[J]. Front Immunol, 2022, 23(5):356. doi: 10.3892/etm.2022.11283.
doi: 10.3892/etm.2022.11283 |
| [5] |
Gu H, Li L, Du M, et al. Key Gene and Functional Pathways Identified in Unexplained Recurrent Spontaneous Abortion Using Targeted RNA Sequencing and Clinical Analysis[J]. Front Immunol, 2021, 12:717832. doi: 10.3389/fimmu.2021.717832.
doi: 10.3389/fimmu.2021.717832 |
| [6] |
Kwiatek M, Gęca T, Kwaśniewska A. Pro- and Anti-Inflammatory Cytokines in the First Trimester-Comparison of Missed Miscarriage and Normal Pregnancy[J]. Int J Environ Res Public Health, 2021, 18(16):8538. doi: 10.3390/ijerph18168538.
doi: 10.3390/ijerph18168538 |
| [7] |
Luo M, Xiao H, Wang L, et al. The expression and clinical significance of three lncRNAs in patients with a missed abortion[J]. Exp Ther Med, 2021, 21(1):8. doi: 10.3892/etm.2020.9440.
doi: 10.3892/etm.2020.9440 pmid: 33235617 |
| [8] |
Zhao Y, Man G, Zhang R, et al. A prospective study comparing the inflammation-related cytokine and chemokine profile from the day of blastocyst transfer to 7 weeks of gestation between pregnancies that did or did not result in a miscarriage[J]. J Reprod Immunol, 2022, 154:103755. doi: 10.1016/j.jri.2022.103755.
doi: 10.1016/j.jri.2022.103755 |
| [9] |
Kaislasuo J, Simpson S, Petersen JF, et al. IL-10 to TNFα ratios throughout early first trimester can discriminate healthy pregnancies from pregnancy losses[J]. Am J Reprod Immunol, 2020, 83(1):e13195. doi: 10.1111/aji.13195.
doi: 10.1111/aji.13195 |
| [10] |
Löb S, Amann N, Kuhn C, et al. Interleukin-1 beta is significantly upregulated in the decidua of spontaneous and recurrent miscarriage placentas[J]. J Reprod Immunol, 2021, 144:103283. doi: 10.1016/j.jri.2021.103283.
doi: 10.1016/j.jri.2021.103283 |
| [11] |
Malyshkina AI, Sotnikova NY, Kroshkina NV, et al. Peculiarities of the content of peripheral blood cytokines in pregnant women with a habitual miscarriage[J]. Klin Lab Diagn, 2020, 65(5):299-303. doi: 10.18821/0869-2084-2020-65-5-299-303.
doi: 10.18821/0869-2084-2020-65-5-299-303 |
| [12] |
Malyshkina AI, Sotnikova NY, Grigushkina EV, et al. Prediction of the outcome of pregnancy in women with reccurent miscarriage[J]. Klin Lab Diagn, 2021, 66(10):618-622. doi: 10.51620/0869-2084-2021-66-10-618-622.
doi: 10.51620/0869-2084-2021-66-10-618-622 |
| [13] |
Vilsmaier T, Amann N, Löb S, et al. The decidual expression of Interleukin-7 is upregulated in early pregnancy loss[J]. Am J Reprod Immunol, 2021, 86(3):e13437. doi: 10.1111/aji.13437.
doi: 10.1111/aji.13437 |
| [14] |
Gupta P, Deo S, Jaiswar SP, et al. Case Control Study to Compare Serum Vascular Endothelial Growth Factor (VEGF) Level in Women with Recurrent Pregnancy Loss (RPL) Compared to Women with Term Pregnancy[J]. J Obstet Gynaecol India, 2019, 69(Suppl 2):95-102. doi: 10.1007/s13224-018-1097-5.
doi: 10.1007/s13224-018-1097-5 |
| [15] |
Zwierzchowska A, Iwan A, Hyc A, et al. Recurrent miscarriage is associated with increased ghrelin mRNA expression in the endometrium- a case-control study[J]. Reprod Biol, 2018, 18(1):12-17. doi: 10.1016/j.repbio.2017.11.003.
doi: S1642-431X(17)30239-5 pmid: 29221937 |
| [16] |
Sajjadi MS, Ghandil P, Shahbazian N, et al. Association of vascular endothelial growth factor A polymorphisms and aberrant expression of connexin 43 and VEGFA with idiopathic recurrent spontaneous miscarriage[J]. J Obstet Gynaecol Res, 2020, 46(3):369-375. doi: 10.1111/jog.14192.
doi: 10.1111/jog.14192 |
| [17] |
Herkiloglu D, Gokce S, Cevik O. Relationship of interferon regulator factor 5 and interferon-γ with missed abortion[J]. Exp Ther Med, 2022, 23(5):356. doi: 10.3892/etm.2022.11283.
doi: 10.3892/etm.2022.11283 pmid: 35493426 |
| [18] |
Comba C, Bastu E, Dural O, et al. Role of inflammatory mediators in patients with recurrent pregnancy loss[J]. Fertil Steril, 2015, 104(6):1467-1474.e1. doi: 10.1016/j.fertnstert.2015.08.011.
doi: 10.1016/j.fertnstert.2015.08.011 pmid: 26368793 |
| [19] |
He Y, Sun Q. IFN-γ induces upregulation of TNF-α, downregulation of MMP-2 and MMP-9 expressions in abortion rat[J]. Eur Rev Med Pharmacol Sci, 2018, 22(15):4762-4767. doi: 10.26355/eurrev_ 201808_15609.
doi: 10.26355/eurrev_ 201808_15609 |
| [20] |
Liu J, Dong P, Jia N, et al. The expression of intracellular cytokines of decidual natural killer cells in unexplained recurrent pregnancy loss[J]. J Matern Fetal Neonatal Med, 2022, 35(16):3209-3215. doi: 10.1080/14767058.2020.1817369.
doi: 10.1080/14767058.2020.1817369 |
| [21] |
李昕, 吴培莉, 朱靓雯, 等. TNF-α及其抑制剂依那西普对URSA患者绒毛外滋养细胞侵袭力的调控作用及机制[J]. 中华妇产科杂志, 2021, 56(10):705-711. doi: 10.3760/cma.j.cn112141-20210610-00315.
doi: 10.3760/cma.j.cn112141-20210610-00315 |
| [22] |
Lv J, Shan X, Yang H, et al. Single Cell Proteomics Profiling Reveals That Embryo-Secreted TNF-α Plays a Critical Role During Embryo Implantation to the Endometrium[J]. Reprod Sci, 2022, 29(5):1608-1617. doi: 10.1007/s43032-021-00833-7.
doi: 10.1007/s43032-021-00833-7 |
| [23] |
Fonseca BM, Cunha SC, Gonçalves D, et al. Decidual NK cell-derived conditioned medium from miscarriages affects endometrial stromal cell decidualisation: endocannabinoid anandamide and tumour necrosis factor-α crosstalk[J]. Hum Reprod, 2020, 35(2):265-274. doi: 10.1093/humrep/dez260.
doi: 10.1093/humrep/dez260 |
| [24] |
Zhang Y, Zhang Y, Li C, et al. NOD1 modulates decidual stromal cell function to maintain pregnancy in the early trimester[J]. Cell Biochem Funct, 2019, 37(7):464-473. doi: 10.1002/cbf.3417.
doi: 10.1002/cbf.3417 pmid: 31396989 |
| [25] |
Samudra AN, Dwyer KM, Selan C, et al. CD39 and CD73 activity are protective in a mouse model of antiphospholipid antibody-induced miscarriages[J]. J Autoimmun, 2018, 88:131-138. doi: 10.1016/j.jaut.2017.10.009.
doi: S0896-8411(17)30591-7 pmid: 29103803 |
| [26] |
Yang SL, Tan HX, Niu TT, et al. Kynurenine promotes the cytotoxicity of NK cells through aryl hydrocarbon receptor in early pregnancy[J]. J Reprod Immunol, 2021, 143:103270. doi: 10.1016/j.jri.2020.103270.
doi: 10.1016/j.jri.2020.103270 |
| [27] |
Huang Q, Ding J, Gong M, et al. Effect of miR-30e regulating NK cell activities on immune tolerance of maternal-fetal interface by targeting PRF1[J]. Biomed Pharmacother, 2019, 109:1478-1487. doi: 10.1016/j.biopha.2018.09.172.
doi: S0753-3322(18)33170-6 pmid: 30551399 |
| [28] |
Stavros S, Mavrogianni D, Papamentzelopoulou M, et al. Association of Tumor Necrosis Factor-α -308G>A, -238G>A and -376G>A polymorphisms with recurrent pregnancy loss risk in the Greek population[J]. Fertil Res Pract, 2021, 7(1):9. doi: 10.1186/s40738-021-00101-x.
doi: 10.1186/s40738-021-00101-x |
| [29] |
Logiodice F, Lombardelli L, Kullolli O, et al. Decidual Interleukin-22-Producing CD4+ T Cells (Th17/Th0/IL-22+ and Th17/Th2/IL-22+, Th2/IL-22+, Th0/IL-22+), Which Also Produce IL-4, Are Involved in the Success of Pregnancy[J]. Int J Mol Sci, 2019, 20(2):428. doi: 10.3390/ijms20020428.
doi: 10.3390/ijms20020428 |
| [30] |
Zhang Q, Tian P, Xu H. MicroRNA-155-5p regulates survival of human decidua stromal cells through NF-κB in recurrent miscarriage[J]. Reprod Biol, 2021, 21(3):100510. doi: 10.1016/j.repbio.2021.100510.
doi: 10.1016/j.repbio.2021.100510 |
| [31] |
Zhao L, Han L, Hei G, et al. Diminished miR-374c-5p negatively regulates IL (interleukin)-6 in unexplained recurrent spontaneous abortion[J]. J Mol Med (Berl), 2022, 100(7):1043-1056. doi: 10.1007/s00109-022-02178-3.
doi: 10.1007/s00109-022-02178-3 pmid: 35689099 |
| [32] |
He S, Ning Y, Ma F, et al. IL-23 Inhibits Trophoblast Proliferation, Migration, and EMT via Activating p38 MAPK Signaling Pathway to Promote Recurrent Spontaneous Abortion[J]. J Microbiol Biotechnol, 2022, 32(6):792-799. doi: 10.4014/jmb.2112.12056.
doi: 10.4014/jmb.2112.12056 |
| [33] |
Li M, Sun F, Qian J, et al. Tim-3/CTLA-4 pathways regulate decidual immune cells-extravillous trophoblasts interaction by IL-4 and IL-10[J]. FASEB J, 2021, 35(8):e21754. doi: 10.1096/fj.202100142R.
doi: 10.1096/fj.202100142R |
| [34] |
Li M, Peng X, Qian J, et al. Galectin-9 regulates HTR8/SVneo function via JNK signaling[J]. Reproduction, 2021, 161(1):1-10. doi: 10.1530/REP-19-0543.
doi: 10.1530/REP-19-0543 pmid: 33112295 |
| [35] |
Salimi E, Karimi-Zarchi M, Dastgheib SA, et al. Association of Promoter Region Polymorphisms of IL-6 and IL-18 Genes with Risk of Recurrent Pregnancy Loss: A Systematic Review and Meta-Analysis[J]. Fetal Pediatr Pathol, 2020, 39(4):346-359. doi: 10.1080/15513815.2019.1652379.
doi: 10.1080/15513815.2019.1652379 pmid: 31437073 |
| [36] |
Soleimani-Jadidi S, Abbasi H, Javaheri A, et al. Cumulative Evidence for Association of IL-10 -1082G>A Polymorphism with Susceptibility to Recurrent Pregnancy Loss: A Systematic Review and Meta-Analysis[J]. Fetal Pediatr Pathol, 2021, 40(5):471-485. doi: 10.1080/15513815.2020.1716903.
doi: 10.1080/15513815.2020.1716903 |
| [37] |
Demir R, Seval Y, Huppertz B. Vasculogenesis and angiogenesis in the early human placenta[J]. Acta Histochem, 2007, 109(4):257-265. doi: 10.1016/j.acthis.2007.02.008.
doi: 10.1016/j.acthis.2007.02.008 pmid: 17574656 |
| [38] |
Liu T, Yan M, Liu F, et al. The role of p53-MDM2 signaling in missed abortion and possible pathogenesis[J]. J Obstet Gynaecol Res, 2022, 48(11):2686-2696. doi: 10.1111/jog.15385.
doi: 10.1111/jog.15385 |
| [39] |
Jing G, Yao J, Dang Y, et al. The role of β-HCG and VEGF-MEK/ERK signaling pathway in villi angiogenesis in patients with missed abortion[J]. Placenta, 2021, 103:16-23. doi: 10.1016/j.placenta.2020.10.005.
doi: 10.1016/j.placenta.2020.10.005 pmid: 33068962 |
| [40] |
Zhi Z, Yang W, Liu L, et al. Early missed abortion is associated with villous angiogenesis via the HIF-1α/VEGF signaling pathway[J]. Arch Gynecol Obstet, 2018, 298(3):537-543. doi: 10.1007/s00404-018-4802-9.
doi: 10.1007/s00404-018-4802-9 pmid: 29951709 |
| [41] |
Zhou G, Li Z, Hu P, et al. miR-219a suppresses human trophoblast cell invasion and proliferation by targeting vascular endothelial growth factor receptor 2 (VEGFR2)[J]. J Assist Reprod Genet, 2021, 38(2):461-470. doi: 10.1007/s10815-020-02022-y.
doi: 10.1007/s10815-020-02022-y |
| [42] |
Amin I, Pandith AA, Manzoor U, et al. Implications of VEGF gene sequence variations and its expression in recurrent pregnancy loss. Reprod Biomed Online[J]. Reprod Biomed Online, 2021, 43(6):1035-1044. doi: 10.1016/j.rbmo.2021.08.009.
doi: 10.1016/j.rbmo.2021.08.009 pmid: 34716101 |
| [43] |
Liang W, Zhu T, Tan N, et al. In missed abortion the decrease of IGF-1 down-regulates PI3K/AKT signaling pathway reducing the secretion of progesterone and β-hCG[J]. Growth Horm IGF Res, 2022, 65:101479. doi: 10.1016/j.ghir.2022.101479.
doi: 10.1016/j.ghir.2022.101479 |
| [44] |
Ardeshir F, Keshavarz L, Asadian F, et al. Role of the 820 A/G variant in the IGF-2 gene and recurrent spontaneous abortion in southern Iran: A cross-sectional study[J]. Int J Reprod Biomed, 2020, 18(9):747-754. doi: 10.18502/ijrm.v13i9.7669.
doi: 10.18502/ijrm.v13i9.7669 |
| [45] |
Yang Y, Wu J, Wang X, et al. Circulating fibroblast growth factor 21 as a potential biomarker for missed abortion in humans[J]. Fertil Steril, 2021, 116(4):1040-1049. doi: 10.1016/j.fertnstert.2021.05.098.
doi: 10.1016/j.fertnstert.2021.05.098 pmid: 34167789 |
| [46] |
Ding J, Yang C, Zhang Y, et al. M2 macrophage-derived G-CSF promotes trophoblasts EMT, invasion and migration via activating PI3K/Akt/Erk1/2 pathway to mediate normal pregnancy[J]. J Cell Mol Med, 2021, 25(4):2136-2147. doi: 10.1111/jcmm.16191.
doi: 10.1111/jcmm.16191 pmid: 33393205 |
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