{"paper_id":"ff6dbd67-e672-402f-8190-d52762c28372","body_text":"Abstract\nBackground\nDifferentially expressed microRNAs (miRNAs) and their target mRNAs may lead to alterations in normal physiological status of the tissues and initiate pathological processes. The aim of this study was to investigate the expression of the most relevant miRNAs in the eutopic endometrial tissue during the window of implantation in women with endometriosis-related infertility.\nMethods\nIn the study, 76 infertile women with a regular menstrual cycle were recruited from the Center for Reproductive Medicine, Peking University Third Hospital between January 2014 and June 2016. We performed a combined messenger RNA and miRNA microarray and bioinformatics analysis of eutopic endometrium in 6 women with and without endometriosis-related infertility at the time of implantation window. Quantitative real-time polymerase chain reaction arrays were utilized to examine the expression levels of selected miRNAs (from 35 patients with endometriosis and 35 disease-free individuals at different menstrual stages).\nResults\nFive differentially expressed miRNAs (miR-142-5p, miR-146a-5p, miR-1281, miR-940, and miR-4634) were significantly upregulated, whereas miR-543 was significantly downregulated in the eutopic endometrium during the window of implantation in patients with endometriosis. Further analysis showed that miR-543 was significantly upregulated at the peri-implantation phase compared with that at proliferative phase in the endometrium of disease-free patients (P <.05). However, the expression level of miR-543 was significantly decreased in patients with endometriosis (P <.05), especially downregulated at the window of implantation phase (P <.05).\nConclusions\nmiR-543 plays an important role during embryo implantation process and is associated with endometrial receptivity. Downregulation of miR-543 may affect embryo implantation, resulting in the pathogenesis of endometriosis-related infertility.\nSimilar content being viewed by others\nReferences\nSimoens S, Hummelshoj L, D’Hooghe T. Endometriosis: cost estimates and methodological perspective. Hum Reprod Update. 2007;13(4):395–404.\nde Ziegler D, Borghese B, Chapron C. Endometriosis and infertility: pathophysiology and management. Lancet. 2010;376(9742):730–738.\nGiudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447):1789–1799.\nWei Q, St Clair JB, Fu T, Stratton P, Nieman LK. Reduced expression of biomarkers associated with the implantation window in women with endometriosis. Fertil Steril. 2009;91(5):1686–1691.\nBulletti C, Coccia ME, Battistoni S, Borini A. Endometriosis and infertility. J Assist Reprod Genet. 2010;27(8):441–447.\nBenagiano G, Brosens I, Habiba M. Structural and molecular features of the endomyometrium in endometriosis and adenomyosis. Hum Reprod Update. 2014;20(3):386–402.\nWilcox AJ, Baird DD, Weinberg CR. Time of implantation of the conceptus and loss of pregnancy. N Engl J Med. 1999;340(23):1796–1799.\nBergh PA, Navot D. The impact of embryonic development and endometrial maturity on the timing of implantation. Fertil Steril. 1992;58(3):537–542.\nAghajanova L, Hamilton AE, Giudice LC. Uterine receptivity to human embryonic implantation: histology, biomarkers, and transcriptomics. Semin Cell Dev Biol. 2008;19:204–211.\nVercellini P, Vigano P, Somigliana E, Fedele L. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol. 2014;10(5):261–275.\nEbert MS, Sharp PA. Roles for microRNAs in conferring robustness to biological processes. Cell. 2012;149(3):515–524.\nSmall EM, Olson EN. Pervasive roles of microRNAs in cardiovascular biology. Nature. 2011;469(7330):336–342.\nWu L, Fan J, Belasco JG. MicroRNAs direct rapid deadenylation of mRNA. Proc Natl Acad Sci U S A. 2006;103(11):4034–4039.\nEvans GE, Martinez-Conejero JA, Phillipson GT, et al. Gene and protein expression signature of endometrial glandular and stromal compartments during the window of implantation. Fertil Steril. 2012;97(6):1365–1373.e1361-e1362.\nPetracco R, Grechukhina O, Popkhadze S, Massasa E, Zhou Y, Taylor HS. MicroRNA 135 regulates HOXA10 expression in endometriosis. J Clin Endocrinol Metab. 2011;96(12):E1925–E1933.\nTeague EM, Print CG, Hull ML. The role of microRNAs in endometriosis and associated reproductive conditions. Hum Reprod Update. 2010;16(2):142–165.\nRevised American Society for Reproductive Medicine Classification of Endometriosis: 1996. Fertil Steril. 1997;67(5):817–821.\nGarrido N, Navarro J, Garcia-Velasco J, Remoh J, Pellice A, Simon C. The endometrium versus embryonic quality in endometriosis-related infertility. Hum Reprod Update. 2002;8(1):95–103.\nShen L, Yang S, Huang W, et al. MicroRNA23a and microRNA23b deregulation derepresses SF-1 and upregulates estrogen signaling in ovarian endometriosis. J Clin Endocrinol Metab. 2013;98(4):1575–1582.\nBurney RO, Hamilton AE, Aghajanova L, et al. MicroRNA expression profiling of eutopic secretory endometrium in women with versus without endometriosis. Mol Hum Reprod. 2009;15(10):625–631.\nLaudanski P, Charkiewicz R, Kuzmicki M, Szamatowicz J, Charkiewicz A, Niklinski J. MicroRNAs expression profiling of eutopic proliferative endometrium in women with ovarian endometriosis. Reprod Biol Endocrinol. 2013;11:78.\nOhlsson Teague EM, Van der Hoek KH, Van der Hoek MB, et al. MicroRNA-regulated pathways associated with endometriosis. Mol Endocrinol. 2009;23(2):265–275.\nFiligheddu N, Gregnanin I, Porporato PE, et al. Differential expression of microRNAs between eutopic and ectopic endometrium in ovarian endometriosis. J Biomed Biotechnol. 2010;2010:369549.\nHawkins SM, Creighton CJ, Han DY, et al. Functional microRNA involved in endometriosis. Mol Endocrinol. 2011;25(5):821–832.\nNaqvi H, Mamillapalli R, Krikun G, Taylor HS. Endometriosis located proximal to or remote from the uterus differentially affects uterine gene expression. Reprod Sci. 2016;23(2):186–191.\nKuokkanen S, Chen B, Ojalvo L, Benard L, Santoro N, Pollard JW. Genomic profiling of microRNAs and messenger RNAs reveals hormonal regulation in microRNA expression in human endometrium. Biol Reprod. 2010;82(4):791–801.\nLi J, Dong G, Wang B, Gao W, Yang Q. miR-543 promotes gastric cancer cell proliferation by targeting SIRT1. Biochem Biophys Res Commun. 2016;469(1):15–21.\nBing L, Hong C, Li-Xin S, Wei G. MicroRNA-543 suppresses endometrial cancer oncogenicity via targeting FAK and TWIST1 expression. Arch Gynecol Obstet. 2014;290(3):533–541.\nChen P, Xu W, Luo Y, et al. MicroRNA 543 suppresses breast cancer cell proliferation, blocks cell cycle and induces cell apoptosis via direct targeting of ERK/MAPK. Onco Targets Ther. 2017;10:1423–1431.\nSong N, Liu H, Ma X, Zhang S. Placental growth factor promotes metastases of ovarian cancer through MiR-543-regulated MMP7. Cell Physiol Biochem. 2015;37(3):1104–1112.\nTaylor HS, Arici A, Olive D, Igarashi P. HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium. J Clin Invest. 1998;101:1379–1384.\nXu B, Geerts D, Bu Z, et al. Regulation of endometrial receptivity by the highly expressed HOXA9, HOXA11 and HOXD10 HOX-class homeobox genes. Hum Reprod. 2014;29(4):781–790.\nCelik O, Unlu C, Otlu B, Celik N, Caliskan E. Laparoscopic endometrioma resection increases peri-implantation endometrial HOXA-10 and HOXA-11 mRNA expression. Fertil Steril. 2015;104(2):356–365.\nApparao KB, Murray MJ, Fritz MA, et al. Osteopontin and its receptor alphavbeta(3) integrin are coexpressed in the human endometrium during the menstrual cycle but regulated differentially. J Clin Endocrinol Metab. 2001;86(10):4991–5000.\nBraza-Boils A, Mari-Alexandre J, Gilabert J, et al. MicroRNA expression profile in endometriosis: its relation to angiogenesis and fibrinolytic factors. Hum Reprod. 2014;29(5):978–988.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nAdditional information\nAuthors’ Note\nPuyu Yang and Zhangxin Wu have contributed equally to this work. All authors are also affiliated with National Clinical Research Center for Obstetrics and Gynecology, Beijing, China 100191; and Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China 100191.\nRights and permissions\nAbout this article\nCite this article\nYang, P., Wu, Z., Ma, C. et al. Endometrial miR-543 Is Downregulated During the Implantation Window in Women With Endometriosis-Related Infertility. Reprod. Sci. 26, 900–908 (2019). https://doi.org/10.1177/1933719118799199\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1177/1933719118799199","source_license":"CC0","license_restricted":false}