Advances in molecular mechanisms of intrauterine adhesions

doi:10.16352/j.issn.1001-6325.2023.04.0547

Abstract

Abstract: Intrauterine adhesions (IUA) is a refractory disease affecting female reproductive health. With the development of medicine, the etiology of IUA has been further studied. At present, the high risk factors that can lead to IUA include: curettage after pregnancy, post-caesarean section, trophoblastocyte disease curettage, postpartum hemorrhage curettage, diagnostic curettage, hysteroscopic surgery, intrauterine device placement, reproductive tract tuberculosis infection, Müllerian duct malformation, etc. Endometrial fibrosis is a main pathological feature. After various signals stimulate different molecular signaling pathways, various growth factors and cytokines interact with each other in vivo to promote the development of fibrosis, which ultimately lead to the occurrence of IUA. At present the current clinical treatment and prevention of IUA is not ideal, especially for moderate and severe IUA. Therefore, the research of the pathogenesis may support the targeted therapy for IUA. This paper aims to review the recent progress in the etiology and molecular mechanism of IUA.

Key words: intrauterine adhesion, curettage, molecular mechanism, TGF-β1

CLC Number:

R711.74

LU Yimeng, TAN Jichun. Advances in molecular mechanisms of intrauterine adhesions[J]. Basic & Clinical Medicine, 2023, 43(4): 547-553.

References 39

[1]	Asherman JG.Amenorrhoea traumatica (atretica)[J].J Obstet Gynaecol Br Emp, 1948, 55: 23-30. doi:10.1111/j.1471-0528.1948.tb07045.x.
[2]	中华医学会妇产科学分会. 宫腔粘连临床诊疗中国专家共识[J]. 中华妇产科杂志, 2015, 50: 881-887.
[3]	Ma J, Zhan H, Li W, et al. Recent trends in therapeutic strategies for repairing endometrial tissue in intrauterine adhesion[J]. Biomater Res, 2021, 25: 40. doi:10.1186/s40824-021-00242-6.
[4]	Schenker JG, Margalioth EJ. Intrauterine adhesions: an updated appraisal[J]. Fertil Steril, 1982, 37: 593-610. doi:10.1016/s0015-0282(16)46268-0.
[5]	Wang Y, Zhao Y, Ge Y, et al. Reproductive outcomes and reproductive tract microbiota shift in women with moderate-to-severe intrauterine adhesions following 30-day post-hysteroscopic placement of balloon stents or intrauterine contraceptive devices: A randomized controlled trial[J]. EClinicalMedicine, 2022, 43: 101200. doi:10.1016/j.eclinm.2021.101200.
[6]	McCausland AM, McCausland VM. Partial rollerball endometrial ablation: a modification of total ablation to treat menorrhagia without causing complications from intrauterine adhesions[J]. Am J Obstet Gynecol, 1999, 180: 1512-1521. doi:10.1016/s0002-9378(99)70047-5.
[7]	Ikemoto Y, Nagai S, Tejima K, et al. Postsurgical intrauterine adhesions after hysteroscopic myomectomy using the myoma pseudocapsule preservation technique evaluated bv second-look hysteroscopy: a retrospective comparative study[J]. J Minim Invasive Gynecol, 2022, 29: 998-1002. doi:10.1016/j.jmig.2022.05.004.
[8]	Huang WJ, Tang XX. Virus infection induced pulmonary fibrosis[J]. J Transl Med, 2021, 19: 496. doi:10.1186/s12967-021-03159-9.
[9]	Xiang R, Li M, Gu Z, et al. Chronic endometritis positively correlates with the aggravation of intrauterine adhesions but has limited effects on reproductive prognosis with antibiotic application[J]. Int J Gynaecol Obstet, 2022. doi:10.1002/ijgo.14434.
[10]	Polishuk WZ, Anteby SO, Weinstein D. Puerperal endometritis and intrauterine adhesions[J]. Int Surg, 1975, 60: 418-420..
[11]	Tal R, Lawal T, Granger E, et al. Genital tuberculosis screening at an academic fertility center in the United States[J]. Am J Obstet Gynecol, 2020, 223: 737.e1-737.e10. doi:10.1016/j.ajog.2020.05.045.
[12]	Stillman RJ, Asarkof N. Association between mullerian duct malformations and Asherman syndrome in infertile women[J]. Obstet Gynecol, 1985, 65: 673-677..
[13]	Zhang Y, Shi L, Lin X, et al. Unresponsive thin endometrium caused by Asherman syndrome treated with umbilical cord mesenchymal stem cells on collagen scaffolds: a pilot study[J]. Stem Cell Res Ther, 2021, 12: 420. doi:10.1186/s13287-021-02499-z.
[14]	Yu C, Xiong C, Tang J, et al. Histone demethylase JMJD3 protects against renal fibrosis by suppressing TGFβ and Notch signaling and preserving PTEN expression[J]. Theranostics, 2021, 11: 2706-2721. doi:10.7150/thno.48679.
[15]	Chen H, Chen H, Liang J, et al. TGF-β1/IL-11/MEK/ERK signaling mediates senescence-associated pulmonary fibrosis in a stress-induced premature senescence model of Bmi-1 deficiency[J]. Exp Mol Med, 2020, 52: 130-151. doi:10.1038/s12276-019-0371-7.
[16]	Zhang Q, Qian D, Tang DD, et al. Glabridin from glycyrrhiza glabra possesses a therapeutic role against keloid via attenuating PI3K/Akt and transforming growth factor-β1/SMAD signaling pathways[J]. J Agric Food Chem, 2022, 70: 10782-10793. doi:10.1021/acs.jafc.2c02045.
[17]	Stolfi C, Troncone E, Marafini I, et al. Role of TGF-Beta and Smad7 in gut inflammation, fibrosis and cancer[J]. Biomolecules, 2020, 11: 17. doi:10.3390/biom11010017.
[18]	Salma U, Xue M, Ali Sheikh MS, et al. Role of transforming growth factor-β1 and Smads signaling pathway in intrauterine adhesion[J]. Mediators Inflamm, 2016, 2016: 4158287. doi:10.1155/2016/4158287.
[19]	Wang H, Che J, Cui K, et al. Schisantherin A ameliorates liver fibrosis through TGF-β1mediated activation of TAK1/MAPK and NF-κB pathways in vitro and in vivo[J]. Phytomedicine, 2021, 88: 153609. doi:10.1016/j.phymed.2021.153609.
[20]	de Souza Basso B, Haute GV, Ortega-Ribera M, et al. Methoxyeugenol deactivates hepatic stellate cells and attenuates liver fibrosis and inflammation through a PPAR-γ and NF-κB mechanism[J]. J Ethnopharmacol, 2021, 280: 114433. doi:10.1016/j.jep.2021.114433.
[21]	Zohny MH, Cavalu S, Youssef ME, et al. Coomassie brilliant blue G-250 dye attenuates bleomycin-induced lung fibrosis by regulating the NF-κB and NLRP3 crosstalk: A novel approach for filling an unmet medical need[J]. Biomed Pharmacother, 2022, 148: 112723. doi:10.1016/j.biopha.2022.112723.
[22]	Xue X, Chen Q, Zhao G, et al. The Overexpression of TGF-β and CCN2 in Intrauterine Adhesions Involves the NF-κB Signaling Pathway[J]. PLoS One, 2015, 10: e0146159. doi:10.1371/journal.pone.0146159.
[23]	Dey A, Varelas X, Guan KL. Targeting the Hippo pathway in cancer, fibrosis, wound healing and regenera-tive medicine[J]. Nat Rev Drug Discov, 2020, 19: 480-494. doi:10.1038/s41573-020-0070-z.
[24]	Mia MM, Cibi DM, Ghani SABA, et al. Loss of Yap/Taz in cardiac fibroblasts attenuates adverse remodelling and improves cardiac function[J]. Cardiovasc Res, 2022, 118: 1785-1804. doi:10.1093/cvr/cvab205.
[25]	Zhu HY, Ge TX, Pan YB, et al. Advanced role of Hippo signaling in endometrial fibrosis: implications for intrauterine adhesion[J]. Chin Med J (Engl), 2017, 130: 2732-2737. doi:10.4103/0366-6999.218013.
[26]	Shen J, Yan J, Wei X, et al. Gant61 ameliorates CCl4-induced liver fibrosis by inhibition of Hedgehog signaling activity[J]. Toxicol Appl Pharmacol, 2020, 387: 114853. doi:10.1016/j.taap.2019.114853.
[27]	Yang X, Sun W, Jing X, et al. C/EBP homologous protein promotes Sonic Hedgehog secretion from type Ⅱ alveolar epithelial cells and activates Hedgehog signaling pathway of fibroblast in pulmonary fibrosis[J]. Respir Res, 2022, 23: 86. doi:10.1186/s12931-022-02012-x.
[28]	Lin X, Zhang Y, Pan Y, et al. Endometrial stem cell-derived granulocyte-colony stimulating factor attenuates endometrial fibrosis via sonic hedgehog transcriptional activator Gli2[J]. Biol Reprod, 2018, 98: 480-490. doi:10.1093/biolre/ioy005.
[29]	Wei C, Pan Y, Zhang Y, et al. Overactivated sonic hedgehog signaling aggravates intrauterine adhesion via inhibiting autophagy in endometrial stromal cells[J]. Cell Death Dis, 2020, 11: 755. doi:10.1038/s41419-020-02956-2.
[30]	Wonnacott A, Denby L, Coward RJM, et al. MicroRNAs and their delivery in diabetic fibrosis[J]. Adv Drug Deliv Rev, 2022, 182: 114045. doi:10.1016/j.addr.2021.114045.
[31]	Ye J, Lin Y, Yu Y, et al. LncRNA NEAT1/microRNA-129-5p/SOCS2 axis regulates liver fibrosis in alcoholic steatohepatitis[J]. J Transl Med, 2020, 18: 445. doi:10.1186/s12967-020-02577-5.
[32]	Tan Q, Xia D, Ying X. miR-29a in exosomes from bone marrow mesenchymal stem cells inhibit fibrosis during endometrial repair of intrauterine adhesion[J]. Int J Stem Cells, 2020, 13: 414-423. doi:10.15283/ijsc20049.
[33]	Chen Y, Sun D, Shang D, et al. miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endome-trial epithelial cells[J]. Open Med (Wars), 2022, 17: 518-526. doi:10.1515/med-2022-0424.
[34]	Sun D, Jiang Z, Chen Y, et al. MiR-455-5p upregulation in umbilical cord mesenchymal stem cells attenuates endometrial injury and promotes repair of damaged endometrium via Janus kinase/signal transducer and activator of transcription 3 signaling[J]. Bioengineered, 2021, 12: 12891-12904. doi:10.1080/21655979.2021.2006976.
[35]	Ye S, Luo W, Khan ZA, et al. Celastrol attenuates angiotensin Ⅱ-induced cardiac remodeling by targeting STAT3[J]. Circ Res, 2020, 126: 1007-1023. doi:10.1161/CIRCRESAHA.119.315861.
[36]	Bensalah M, Muraine L, Boulinguiez A, et al. A negative feedback loop between fibroadipogenic progenitors and muscle fibres involving endothelin promotes human muscle fibrosis[J]. J Cachexia Sarcopenia Muscle, 2022, 13: 1771-1784. doi:10.1002/jcsm.12974.
[37]	Strieter RM, Gomperts BN, Keane MP. The role of CXC chemokines in pulmonary fibrosis[J]. J Clin Invest, 2007, 117: 549-556. doi:10.1172/JCI30562.
[38]	Wilkinson-Berka JL. Angiotensin and diabetic retinopathy[J]. Int J Biochem Cell Biol, 2006, 38: 752-765. doi:10.1016/j.biocel.2005.08.002.
[39]	Zhang M, Sui W, Xing Y, et al. Angiotensin Ⅳ attenuates diabetic cardiomyopathy via suppressing FoxO1-induced excessive autophagy, apoptosis and fibrosis[J]. Theranostics, 2021, 11: 8624-8639. doi:10.7150/thno.48561.