子宫内膜容受性与白血病抑制因子的相关性

doi:10.12280/gjszjk.20220168

摘要/Abstract

摘要：

子宫内膜容受性在胚胎植入中起关键作用,约2/3的胚胎植入失败是由于子宫内膜容受性不佳。白血病抑制因子（leukemia inhibitory factor,LIF）是子宫内膜容受性的重要生物学标志物之一,其在种植窗子宫内膜腺上皮高表达,参与调控胚胎植入过程中子宫上皮细胞的信号转导,将子宫内膜从非接受状态转化为接受状态。LIF表达异常可使子宫内膜容受性受损,与不孕症的发生密切相关,且其表达具有类固醇激素依赖性,并受多种细胞因子和生长因子调控。综述LIF在子宫内膜容受性的建立、胚胎植入、子宫内膜蜕膜化过程中的表达、相关信号转导通路及影响因素的研究进展,以期为子宫内膜容受性的诊治提供新的思路。

关键词: 白血病抑制因子, 胚胎植入, 蜕膜, 信号传导, 子宫内膜容受性

Abstract:

Endometrial receptivity plays a key role in embryo implantation, and 2/3 of embryo implantation failures are due to poor endometrial receptivity. Leukemia inhibitory factor (LIF) is an important biological marker of endometrial receptivity. The expression of LIF is highly upregulated in the endometrial glandular epithelium during the implantation window. LIF participates in the regulation of signal transduction of endometrial epithelial cells during embryo implantation, which may transform the endometrium from a non-receptive state to a receptive state. Abnormal expression of LIF impaires endometrial receptivity, which is closely related to the occurrence of infertility. Studies have showed that the expression of LIF is steroid-dependent, and that the expression can also be regulated by a variety of cytokines and growth factors. This paper describes the expression of LIF, signal transduction pathway and influencing factors of LIF expression in the establishment of endometrial receptivity, embryo implantation and decidualization, providing new ideas for the diagnosis and treatment of endometrial receptivity.

Key words: Leukemia inhibitory factor, Embryo implantation, Decidua, Signal transduction, Endometrial receptivity

张晓轩, 翟超, 李光璨, 任春娥. 子宫内膜容受性与白血病抑制因子的相关性[J]. 国际生殖健康/计划生育, 2022, 41(4): 327-331.

ZHANG Xiao-xuan, ZHAI Chao, LI Guang-can, REN Chun-e. Leukemia Inhibitory Factor Related to Endometrial Receptivity[J]. Journal of International Reproductive Health/Family Planning, 2022, 41(4): 327-331.

参考文献 34

[1]	Lessey BA, Young SL. What exactly is endometrial receptivity?[J]. Fertil Steril, 2019, 111(4):611-617. doi: 10.1016/j.fertnstert.2019.02.009. doi: S0015-0282(19)30120-7 pmid: 30929718
[2]	Monsivais D, Nagashima T, Prunskaite-Hyyrylainen R, et al. Endometrial receptivity and implantation require uterine BMP signaling through an ACVR2A-SMAD1/SMAD5 axis[J]. Nat Commun, 2021, 12(1):3386. doi: 10.1038/s41467-021-23571-5. doi: 10.1038/s41467-021-23571-5
[3]	Jain M, Samokhodskaya L, Mladova E, et al. Mucosal biomarkers for endometrial receptivity: A promising yet underexplored aspect of reproductive medicine[J]. Syst Biol Reprod Med, 2022, 68(1):13-24. doi: 10.1080/19396368.2021.1985186. doi: 10.1080/19396368.2021.1985186 URL
[4]	Hawkins BL, Fritz MA, Wu SP, et al. Poor Endometrial Proliferation After Clomiphene is Associated With Altered Estrogen Action[J]. J Clin Endocrinol Metab, 2021, 106(9):2547-2565. doi: 10.1210/clinem/dgab381. doi: 10.1210/clinem/dgab381 URL
[5]	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
[6]	Nicola NA, Babon JJ. Leukemia inhibitory factor (LIF)[J]. Cytokine Growth Factor Rev, 2015, 26(5):533-544. doi: 10.1016/j.cytogfr.2015.07.001. doi: 10.1016/j.cytogfr.2015.07.001 URL
[7]	Shan L, Zhou Y, Peng S, et al. Implantation failure in rats with subclinical hypothyroidism is associated with LIF/STAT3 signaling[J]. Endocr Connect, 2019, 8(6):718-727. doi: 10.1530/EC-19-0185. doi: 10.1530/EC-19-0185 URL
[8]	Hiraoka T, Hirota Y, Fukui Y, et al. Differential roles of uterine epithelial and stromal STAT3 coordinate uterine receptivity and embryo attachment[J]. Sci Rep, 2020, 10(1):15523. doi: 10.1038/s41598-020-72640-0. doi: 10.1038/s41598-020-72640-0
[9]	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
[10]	Dhakal P, Fitzgerald HC, Kelleher AM, et al. Uterine glands impact embryo survival and stromal cell decidualization in mice[J]. FASEB J, 2021, 35(10):e21938. doi: 10.1096/fj.202101170RR. doi: 10.1096/fj.202101170RR
[11]	Cheng J, Rosario G, Cohen TV, et al. Tissue-Specific Ablation of the LIF Receptor in the Murine Uterine Epithelium Results in Implantation Failure[J]. Endocrinology, 2017, 158(6):1916-1928. doi: 10.1210/en.2017-00103. doi: 10.1210/en.2017-00103 URL
[12]	Patel B, Elguero S, Thakore S, et al. Role of nuclear progesterone receptor isoforms in uterine pathophysiology[J]. Hum Reprod Update, 2015, 21(2):155-173. doi: 10.1093/humupd/dmu056. doi: 10.1093/humupd/dmu056 URL
[13]	Matsuo M, Hirota Y, Fukui Y, et al. Levonorgestrel Inhibits Embryo Attachment by Eliminating Uterine Induction of Leukemia Inhibitory Factor[J]. Endocrinology, 2020, 161(2):bqz005. doi: 10.1210/endocr/bqz005. doi: 10.1210/endocr/bqz005 URL
[14]	Hajipour H, Farzadi L, Roshangar L, et al. A human chorionic gonadotropin (hCG) delivery platform using engineered uterine exosomes to improve endometrial receptivity[J]. Life Sci, 2021, 275:119351. doi: 10.1016/j.lfs.2021.119351. doi: 10.1016/j.lfs.2021.119351 URL
[15]	Hu W, Feng Z, Teresky AK, et al. p53 regulates maternal reproduction through LIF[J]. Nature, 2007, 450(7170):721-724. doi: 10.1038/nature05993. doi: 10.1038/nature05993 URL
[16]	Sini I, Handayani N, Harahap A, et al. Role of three-dimensional Doppler ultrasonography and leukemia inhibitory factor from endometrial secretion in predicting endometrial receptivity in IVF treatment: a pilot study[J]. Arch Gynecol Obstet, 2022 Feb 28. doi: 10.1007/s00404-022-06450-2. doi: 10.1007/s00404-022-06450-2
[17]	Moharrami T, Ai J, Ebrahimi-Barough S, et al. Influence of Follicular Fluid and Seminal Plasma on The Expression of Endometrial Receptivity Genes in Endometrial Cells[J]. Cell J, 2021, 22(4):457-466. doi: 10.22074/cellj.2021.6851. doi: 10.22074/cellj.2021.6851
[18]	Subramani E, Madogwe E, Ray CD, et al. Dysregulated leukemia inhibitory factor and its receptor regulated signal transducers and activators of transcription 3 pathway: a possible cause for repeated implantation failure in women with dormant genital tuberculosis?[J]. Fertil Steril, 2016, 105(4):1076-1084. doi: 10.1016/j.fertnstert.2015.12.015. doi: 10.1016/j.fertnstert.2015.12.015 URL
[19]	Cha J, Sun X, Dey SK. Mechanisms of implantation: strategies for successful pregnancy[J]. Nat Med, 2012, 18(12):1754-1767. doi: 10.1038/nm.3012. doi: 10.1038/nm.3012 URL
[20]	Zhang S, Lin H, Kong S, et al. Physiological and molecular determinants of embryo implantation[J]. Mol Aspects Med, 2013, 34(5):939-980. doi: 10.1016/j.mam.2012.12.011. doi: 10.1016/j.mam.2012.12.011 URL
[21]	Nejatbakhsh R, Kabir-Salmani M, Dimitriadis E, et al. Subcellular localization of L-selectin ligand in the endometrium implies a novel function for pinopodes in endometrial receptivity[J]. Reprod Biol Endocrinol, 2012, 10:46. doi: 10.1186/s12958-021-00745-w. doi: 10.1186/s12958-021-00745-w URL
[22]	Fukui Y, Hirota Y, Aikawa S, et al. Uterine Receptivity is Reflected by LIF Expression in the Cervix[J]. Reprod Sci, 2021, 29(5):1457-1462. doi: 10.1007/s43032-021-00816-8. doi: 10.1007/s43032-021-00816-8 URL
[23]	Yuan L, Feng F, Mao Z, et al. Regulation mechanism of miR-494-3p on endometrial receptivity in mice via PI3K/AKT/mTOR pathway[J]. Gen Physiol Biophys, 2021, 40(5):351-363. doi: 10.4149/gpb_2021021. doi: 10.4149/gpbˍ2021021 pmid: 34602449
[24]	Craciunas L, Gallos I, Chu J, et al. Conventional and modern markers of endometrial receptivity: a systematic review and meta-analysis[J]. Hum Reprod Update, 2019, 25(2):202-223. doi: 10.1093/humupd/dmy044. doi: 10.1093/humupd/dmy044 URL
[25]	Cadoret V, Jarrier-Gaillard P, Papillier P, et al. Leukaemia inhibitory factor modulates the differentiation of granulosa cells during sheep in vitro preantral to antral follicle development and improves oocyte meiotic competence[J]. Mol Hum Reprod, 2021, 27(9):gaab051. doi: 10.1093/molehr/gaab051. doi: 10.1093/molehr/gaab051 URL
[26]	Kimber SJ, Sneddon SF, Bloor DJ, et al. Expression of genes involved in early cell fate decisions in human embryos and their regulation by growth factors[J]. Reproduction, 2008, 135(5):635-647. doi: 10.1530/REP-07-0359. doi: 10.1530/REP-07-0359 pmid: 18411410
[27]	Hosseini A, Movaghar B, Abkenari SA, et al. Leukemia inhibitory factor enhanced the developmental and implantation compatibility of mouse embryos in co-culture with human endometrial epithelial cells[J]. Reprod Dev Med, 2021, 5(4):199-205. doi: 10.4103/2096-2924.327881. doi: 10.4103/2096-2924.327881
[28]	Dhar R, Singh S, Mukherjee I, et al. EMTiness in pseudo-malignant behavior of trophoblasts during embryo implantation[J]. Front Biosci(Landmark Ed), 2021, 26(4):717-743. doi: 10.2741/4915. doi: 10.2741/4915
[29]	Tapia A, Salamonsen LA, Manuelpillai U, et al. Leukemia inhibitory factor promotes human first trimester extravillous trophoblast adhesion to extracellular matrix and secretion of tissue inhibitor of metalloproteinases-1 and -2[J]. Hum Reprod, 2008, 23(8):1724-1732. doi: 10.1093/humrep/den121. doi: 10.1093/humrep/den121 URL
[30]	Zhu YY, Wu Y, Chen ST, et al. In situ Synthesized Monosodium Urate Crystal Enhances Endometrium Decidualization via Sterile Inflammation During Pregnancy[J]. Front Cell Dev Biol, 2021, 9:702590. doi: 10.3389/fcell.2021.702590. doi: 10.3389/fcell.2021.702590 URL
[31]	Shuya LL, Menkhorst EM, Yap J, et al. Leukemia inhibitory factor enhances endometrial stromal cell decidualization in humans and mice[J]. PLoS One, 2011, 6(9):e25288. doi: 10.1371/journal.pone.0025288. doi: 10.1371/journal.pone.0025288 URL
[32]	Zhou R, Wildt DE, Keefer CL, et al. Combinations of Growth Factors Regulating LIF/STAT3, WNT, and FGF2 Pathways Sustain Pluripotency-Related Proteins in Cat Embryonic Cells[J]. Stem Cells Dev, 2019, 28(5):329-340. doi: 10.1089/scd.2018.0109. doi: 10.1089/scd.2018.0109 pmid: 30698497
[33]	Yuan MY, Chang D, Xie TT, et al. Uterine Expression of WNT7A and β-catenin After Induction of Oestrus in Sheep[J]. J Northeast Agricultural University(English Edition), 2021, 28(1):61-74.
[34]	Dunlap KA, Filant J, Hayashi K, et al. Postnatal deletion of Wnt7a inhibits uterine gland morphogenesis and compromises adult fertility in mice[J]. Biol Reprod, 2011, 85(2):386-396. doi: 10.1095/biolreprod.111.091769. doi: 10.1095/biolreprod.111.091769