{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:58:58Z","timestamp":1792803538327,"version":"4.5.0"},"reference-count":111,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Cluj-Napoca, Romania","award":["92\/10.04.2025"],"award-info":[{"award-number":["92\/10.04.2025"]}],"id":[{"id":"https:\/\/ror.org\/051h0cw83","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>HOX genes, a family of conserved transcription factors, are critical for reproductive tract development and endometrial functionality. This review highlights the molecular underpinnings of HOXA10\/HOXA11 in reproductive health and their dysregulation in benign pathologies associated with infertility, such as endometriosis, adenomyosis, and endometrial polyps. These genes are dynamically regulated by estrogen and progesterone, with peak expression during the secretory phase of the menstrual cycle when implantation takes place. The molecular mechanisms underlying their action include the modulation of extracellular matrix (ECM) remodeling via metalloproteinases, cytokines like leukemia inhibitory factor, and cell adhesion molecules such as \u03b23-integrin, all of which are essential for the differentiation of epithelial and stromal cells, as well as for trophoblast invasion. Aberrant HOX gene expression, driven by DNA hypermethylation or altered histone acetylation, compromises endometrial receptivity and implantation. For instance, reduced HOXA10 expression in endometriosis stems from hypermethylation and chronic inflammation, disrupting immune modulation and cytokine signaling. Similarly, adenomyosis alters HOXA11-regulated ECM remodeling and \u03b23-integrin expression, impairing embryo attachment. Furthermore, regulatory pathways involving vitamin D and retinoic acid offer promising therapeutic avenues pathways, as they enhance HOXA10\/HOXA11 expression and endometrial receptivity. This review underscores the critical molecular roles of HOXA10\/HOXA11 genes as biomarkers and therapeutic targets to optimize fertility outcomes and address reproductive pathologies.<\/jats:p>","DOI":"10.3390\/biom15040563","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T10:47:41Z","timestamp":1744282061000},"page":"563","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["HOXA10 and HOXA11 in Human Endometrial Benign Disorders: Unraveling Molecular Pathways and Their Impact on Reproduction"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0975-5200","authenticated-orcid":false,"given":"Lorin-Manuel","family":"P\u00eerlog","sequence":"first","affiliation":[{"name":"Department of Molecular Sciences, Faculty of Medicine, University of Medicine and Pharmacy \u201cIuliu Ha\u021bieganu\u201d, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrada-Adelaida","family":"P\u0103tr\u0103\u0219canu","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, Faculty of Medicine, University of Medicine and Pharmacy \u201cIuliu Ha\u021bieganu\u201d, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara-Diana","family":"Ona","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, Faculty of Medicine, University of Medicine and Pharmacy \u201cIuliu Ha\u021bieganu\u201d, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea","family":"C\u0103tan\u0103","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, Faculty of Medicine, University of Medicine and Pharmacy \u201cIuliu Ha\u021bieganu\u201d, 400012 Cluj-Napoca, Romania"},{"name":"Regional Laboratory Cluj-Napoca, Department of Medical Genetics, Regina Maria Health Network, 400363 Cluj-Napoca, Romania"},{"name":"Department of Oncogenetics, \u201cProf. Dr. I. Chiricu\u021b\u0103\u201d Institute of Oncology, 400015 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7700-2384","authenticated-orcid":false,"given":"Ioana Cristina","family":"Rotar","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, Faculty of Medicine, University of Medicine and Pharmacy \u201cIuliu Ha\u021bieganu\u201d, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1177\/1933719116657196","article-title":"Endometrial expression of homeobox genes and cell adhesion molecules in infertile women with intramural fibroids during window of implantation","volume":"24","author":"Makker","year":"2016","journal-title":"Reprod. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/ame2.12002","article-title":"Homeobox genes for embryo implantation: From mouse to human","volume":"1","author":"He","year":"2018","journal-title":"Anim. Models Exp. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"a023002","DOI":"10.1101\/cshperspect.a023002","article-title":"The role of Hox Genes in female reproductive tract development, adult function, and fertility","volume":"6","author":"Du","year":"2015","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jsbmb.2018.04.008","article-title":"Polycystic ovary syndrome (PCOS), an inflammatory, systemic, lifestyle endocrinopathy","volume":"182","author":"Patel","year":"2018","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e1071","DOI":"10.1210\/clinem\/dgaa839","article-title":"Update on PCOS: Consequences, challenges, and guiding treatment","volume":"106","author":"Hoeger","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_6","unstructured":"(2025, January 07). Polycystic Ovary Syndrome. Available online: https:\/\/www.eshre.eu\/Guidelines-and-Legal\/Guidelines\/Polycystic-Ovary-Syndrome."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"The Lancet Regional Health\u2014Europe (2022). Polycystic Ovary Syndrome: What More Can Be Done Patients?. Lancet Reg. Health Eur., 21, 100524.","DOI":"10.1016\/j.lanepe.2022.100524"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100326","DOI":"10.1016\/j.clinsp.2024.100326","article-title":"It is time to change the definition: Endometriosis is no longer a pelvic disease","volume":"79","year":"2024","journal-title":"Clinics"},{"key":"ref_9","unstructured":"Gunther, R., and Walker, C. (2025, January 07). Adenomyosis. StatPearls\u2014NCBI Bookshelf, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK539868\/."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1093\/humrep\/dew307","article-title":"The natural history of endometrial polyps","volume":"32","author":"Wong","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.fertnstert.2007.05.072","article-title":"Location of endometrial polyp and pregnancy rate in infertility patients","volume":"90","author":"Yanaihara","year":"2007","journal-title":"Fertil. Steril."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1016\/j.fertnstert.2009.02.016","article-title":"Novel finding of high density of activated mast cells in endometrial polyps","volume":"92","author":"Black","year":"2009","journal-title":"Fertil. Steril."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1002\/uog.6259","article-title":"Prevalence of endometrial polyps and abnormal uterine bleeding in a Danish population aged 20\u201374 years","volume":"33","author":"Dreisler","year":"2008","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2050312119848247","DOI":"10.1177\/2050312119848247","article-title":"Endometrial polyps: Pathogenesis, sequelae and treatment","volume":"7","author":"Nijkang","year":"2019","journal-title":"SAGE Open Medicine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e2243951","DOI":"10.1001\/jamanetworkopen.2022.43951","article-title":"Risk of endometrial polyps, hyperplasia, carcinoma, and uterine cancer after tamoxifen treatment in premenopausal women with breast cancer","volume":"5","author":"Ryu","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1080\/09513590.2021.1958310","article-title":"Polycystic ovarian syndrome and infertility: Overview and insights of the putative treatments","volume":"37","author":"Mawet","year":"2021","journal-title":"Gynecol. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bonavina, G., and Taylor, H.S. (2022). Endometriosis-associated infertility: From pathophysiology to tailored treatment. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1020827"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1097\/OGX.0000000000000346","article-title":"The impact of adenomyosis on women\u2019s fertility","volume":"71","author":"Harada","year":"2016","journal-title":"Obstet. Gynecol. Surv."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s13224-016-0929-4","article-title":"Endometrial polyps and subfertility","volume":"67","author":"Chami","year":"2016","journal-title":"J. Obstet. Gynecol. India"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.bpobgyn.2016.09.005","article-title":"Endometrial Polyps and Abnormal Uterine Bleeding (AUB-P): What is the relationship, how are they diagnosed and how are they treated?","volume":"40","author":"Clark","year":"2016","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s00404-007-0460-z","article-title":"Pregnancy rates after hysteroscopic polypectomy depending on the size or number of the polyps","volume":"277","author":"Stamatellos","year":"2007","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Fang, W., Li, K., Ma, S., Wei, F., and Hu, Y. (2023). Natural selection and convergent evolution of the HOX gene family in Carnivora. Front. Ecol. Evol., 11.","DOI":"10.3389\/fevo.2023.1107034"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"dev192476","DOI":"10.1242\/dev.192476","article-title":"Hox genes in development and beyond","volume":"150","author":"Hubert","year":"2023","journal-title":"Development"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Afzal, Z., and Krumlauf, R. (2022). Transcriptional regulation and implications for controlling Hox gene expression. J. Dev. Biol., 10.","DOI":"10.3390\/jdb10010004"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"444","DOI":"10.2174\/1389202917666160616082436","article-title":"Hox Gene collinearity: From A-P patterning to radially symmetric animals","volume":"17","author":"Papageorgiou","year":"2016","journal-title":"Curr. Genom."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Papageorgiou, S. (2021). Physical laws shape up HOX gene collinearity. J. Dev. Biol., 9.","DOI":"10.20944\/preprints202103.0450.v2"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3569493","DOI":"10.1155\/2018\/3569493","article-title":"Role of HOX genes in stem cell differentiation and cancer","volume":"2018","author":"Bhatlekar","year":"2018","journal-title":"Stem Cells Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3728","DOI":"10.21037\/tcr-23-2146","article-title":"Comprehensive analysis of HOX family genes in endometrial cancer","volume":"12","author":"Zhao","year":"2023","journal-title":"Transl. Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/s41408-024-01004-y","article-title":"Regulation of HOX gene expression in AML","volume":"14","author":"Khan","year":"2024","journal-title":"Blood Cancer J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1387\/ijdb.190120dm","article-title":"Homeobox genes in endometrium: From development to decidualization","volume":"64","author":"Ashary","year":"2020","journal-title":"Int. J. Dev. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ekanayake, D.L., Ma\u0142opolska, M.M., Schwarz, T., Tuz, R., and Bartlewski, P.M. (2022). The roles and expression of HOXA\/Hoxa10 gene: A prospective marker of mammalian female fertility?. Reprod. Biol., 22.","DOI":"10.1016\/j.repbio.2022.100647"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"17057","DOI":"10.1038\/cddiscovery.2017.57","article-title":"Enhanced HOXA10 sumoylation inhibits embryo implantation in women with recurrent implantation failure","volume":"3","author":"Jiang","year":"2017","journal-title":"Cell Death Discovery"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1007\/s00467-022-05814-9","article-title":"HOXA11 is another monogenic cause of congenital anomalies of the kidney and urinary tract\u2014Reply","volume":"38","author":"Kagan","year":"2022","journal-title":"Pediatr. Nephrol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1182\/blood.V114.22.142.142","article-title":"The HOX11\/TLX1 transcription factor oncogene induces chromosomal aneuploidy in T-ALL","volume":"114","author":"Luna","year":"2009","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"117230","DOI":"10.1016\/j.lfs.2019.117230","article-title":"HOXC11 functions as a novel oncogene in human colon adenocarcinoma and kidney renal clear cell carcinoma","volume":"243","author":"Cui","year":"2020","journal-title":"Life Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1210\/er.2005-0018","article-title":"Endocrine regulation of HOX genes","volume":"27","author":"Daftary","year":"2006","journal-title":"Endocr. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.3892\/ijo.2012.1660","article-title":"The prolactin receptor mediates HOXA1-stimulated oncogenicity in mammary carcinoma cells","volume":"41","author":"Hou","year":"2012","journal-title":"Int. J. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13148-015-0168-z","article-title":"The influence of menstrual cycle and endometriosis on endometrial methylome","volume":"8","author":"Saare","year":"2016","journal-title":"Clin. Epigenet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1210\/en.2011-0047","article-title":"Evolution of the Insulin-Like Growth Factor binding Protein (IGFBP) family","volume":"152","author":"Daza","year":"2011","journal-title":"Endocrinology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1093\/abbs\/gmaa173","article-title":"Identification of HOXA10 target genes in human endometrial stromal cells by RNA-seq analysis","volume":"53","author":"Wang","year":"2020","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Marquardt, R.M., Kim, T.H., Shin, J.-H., and Jeong, J.-W. (2019). Progesterone and estrogen signaling in the endometrium: What goes wrong in endometriosis?. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153822"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1093\/biolre\/ioac007","article-title":"HOXA10 improves endometrial receptivity by upregulating E-cadherin","volume":"106","author":"Bi","year":"2022","journal-title":"Biol. Reprod."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"252","DOI":"10.4103\/ijem.ijem_90_22","article-title":"Induction of endometrial HOXA 10 gene expression by vitamin D and its possible influence on reproductive outcome of PCOS patients undergoing ovulation induction procedure","volume":"26","author":"Shilpasree","year":"2022","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s11154-024-09923-8","article-title":"Role of HOXA10 in pathologies of the endometrium","volume":"26","author":"Mishra","year":"2024","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.rbmo.2017.06.016","article-title":"Pathogenesis of adenomyosis: An update on molecular mechanisms","volume":"35","author":"Vannuccini","year":"2017","journal-title":"Reprod. BioMed. Online"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nrc2826","article-title":"The Hox genes and their roles in oncogenesis","volume":"10","author":"Shah","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/s41587-020-0546-8","article-title":"Visualizing and interpreting cancer genomics data via the Xena platform","volume":"38","author":"Goldman","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"104871","DOI":"10.1016\/j.yexmp.2023.104871","article-title":"DNA methylation of HOX genes and its clinical implications in cancer","volume":"134","author":"Hu","year":"2023","journal-title":"Exp. Mol. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Fan, F., Mo, H., Zhang, H., Dai, Z., Wang, Z., Qu, C., Liu, F., Zhang, L., Luo, P., and Zhang, J. (2022). HOXA5: A crucial transcriptional factor in cancer and a potential therapeutic target. Biomed. Pharmacother., 155.","DOI":"10.1016\/j.biopha.2022.113800"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Ding, F., Chen, P., Bie, P., Piao, W., and Cheng, Q. (2021). HOXA5 is recognized as a Prognostic-Related biomarker and promotes glioma progression through affecting cell cycle. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.633430"},{"key":"ref_51","first-page":"5096","article-title":"Pan-cancer analysis of Homeobox B9 as a predictor for prognosis and immunotherapy in human tumors","volume":"51","author":"Jin","year":"2023","journal-title":"Aging"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1007\/s00109-014-1181-y","article-title":"HOX genes and their role in the development of human cancers","volume":"92","author":"Bhatlekar","year":"2014","journal-title":"J. Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1530\/JME-22-0051","article-title":"Loss of HOXA10 causes endometrial hyperplasia progressing to endometrial cancer","volume":"69","author":"Mishra","year":"2022","journal-title":"J. Mol. Endocrinol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"R85","DOI":"10.1530\/ERC-15-0218","article-title":"Tumor progression, metastasis, and modulators of epithelial\u2013mesenchymal transition in endometrioid endometrial carcinoma: An update","volume":"23","author":"Makker","year":"2015","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Lazim, N., Elias, M.H., Sutaji, Z., Karim, A.K.A., Abu, M.A., Ugusman, A., Syafruddin, S.E., Mokhtar, M.H., and Ahmad, M.F. (2023). Expression of HOXA10 Gene in Women with Endometriosis: A Systematic Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241612869"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1007\/s10815-010-9471-y","article-title":"The role of the Hoxa10\/HOXA10 gene in the etiology of endometriosis and its related infertility: A review","volume":"27","author":"Zanatta","year":"2010","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_57","first-page":"43","article-title":"HOXA-10 gene expression in ectopic and eutopic endometrium tissues: Does it differ between fertile and infertile women with endometriosis?","volume":"233","year":"2018","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Camboni, A., and Marbaix, E. (2021). Ectopic Endometrium: The Pathologist\u2019s perspective. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222010974"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Kulebyakina, M., and Makarevich, P. (2020). Hox-Positive adult mesenchymal stromal cells: Beyond positional identity. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00624"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Elias, M.H., Lazim, N., Sutaji, Z., Abu, M.A., Karim, A.K.A., Ugusman, A., Syafruddin, S.E., Mokhtar, M.H., and Ahmad, M.F. (2023). HOXA10 DNA Methylation Level in the Endometrium Women with Endometriosis: A Systematic Review. Biology, 12.","DOI":"10.3390\/biology12030474"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.humpath.2020.03.005","article-title":"The significance of recurrence in endometrial polyps: A clinicopathologic analysis","volume":"100","author":"Ciscato","year":"2020","journal-title":"Hum. Pathol."},{"key":"ref_62","first-page":"8895","article-title":"The association between endometrial polyps, chronic endometritis, and IVF outcomes","volume":"27","author":"Vaduva","year":"2023","journal-title":"PubMed"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.fertnstert.2019.02.008","article-title":"Uterine polyps, adenomyosis, leiomyomas, and endometrial receptivity","volume":"111","author":"Munro","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Vitagliano, A., Cialdella, M., Cicinelli, R., Santarsiero, C.M., Greco, P., Buzzaccarini, G., Noventa, M., and Cicinelli, E. (2021). Association between Endometrial Polyps and Chronic Endometritis: Is It Time for a Paradigm Shift in the Pathophysiology of Endometrial Polyps in Pre-Menopausal Women? Results of a Systematic Review and Meta-Analysis. Diagnostics, 11.","DOI":"10.3390\/diagnostics11122182"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Cicinelli, E., Vitagliano, A., Loizzi, V., De Ziegler, D., Fanelli, M., Bettocchi, S., Nardelli, C., Trojano, G., Cicinelli, R., and Minervini, C.F. (2021). Altered Gene Expression Encoding Cytochines, Grow Factors and Cell Cycle Regulators in the Endometrium of Women with Chronic Endometritis. Diagnostics, 11.","DOI":"10.3390\/diagnostics11030471"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.jmig.2018.07.024","article-title":"Higher Prevalence of Endometrial Polyps in Patients with Fallopian Tube Obstruction: A Case-control Study","volume":"26","author":"Sun","year":"2018","journal-title":"J. Minim. Invasive Gynecol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1016\/j.jmig.2021.04.011","article-title":"Is Chronic Endometritis Associated with Tubal Infertility? A Prospective Cohort Study","volume":"28","author":"Holzer","year":"2021","journal-title":"J. Minim. Invasive Gynecol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.2147\/IJWH.S434299","article-title":"Association between endometritis and endometrial polyp: A Mendelian randomization study","volume":"15","author":"Wei","year":"2023","journal-title":"Int. J. Women Health"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3474","DOI":"10.1093\/humrep\/des323","article-title":"Local mononuclear cell infiltrates in infertile patients with endometrial macropolyps versus micropolyps","volume":"27","author":"Kitaya","year":"2012","journal-title":"Hum. Reprod."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1111\/jog.14541","article-title":"Multiple endometrial polyps is associated with higher risk of chronic endometritis in reproductive-aged women","volume":"47","author":"Guo","year":"2020","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1177\/19458924211049867","article-title":"Chronic rhinosinusitis with nasal polyposis (CRSwNP): The correlation between expression of Galectin-10 and Clinical-Cytological Grading (CCG)","volume":"36","author":"Gelardi","year":"2021","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Ashktorab, H., Brim, H., Hassan, S., Nouraie, M., Gebreselassie, A., Laiyemo, A.O., Kibreab, A., Aduli, F., Latella, G., and Brant, S.R. (2020). Inflammatory polyps occur more frequently in inflammatory bowel disease than other colitis patients. BMC Gastroenterol., 20.","DOI":"10.1186\/s12876-020-01279-y"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1111\/aji.12277","article-title":"Comprehensive Endometrial Immunoglobulin Subclass Analysis in Infertile Women Suffering from Repeated Implantation Failure with or without Chronic Endometritis","volume":"72","author":"Kitaya","year":"2014","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.fertnstert.2019.09.001","article-title":"Evaluation of peripheral and uterine immune status of chronic endometritis in patients with recurrent reproductive failure","volume":"113","author":"Li","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_75","first-page":"6809","article-title":"Fresh vs. frozen embryo transfer in assisted reproductive techniques: A single center retrospective cohort study and ethical-legal implications","volume":"27","author":"Gullo","year":"2023","journal-title":"PubMed"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Pai, P., and Sukumar, S. (2020). HOX genes and the NF-\u03baB pathway: A convergence of developmental biology, inflammation and cancer biology. Biochim. Biophys. Acta (BBA) Rev. Cancer, 1874.","DOI":"10.1016\/j.bbcan.2020.188450"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/33429","article-title":"Role of Rel\/NF-\u03baB transcription factors during the outgrowth of the vertebrate limb","volume":"392","author":"Kanegae","year":"1998","journal-title":"Nature"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"13893","DOI":"10.1080\/21655979.2022.2086377","article-title":"Long non-coding RNA HOXA11-AS knockout inhibits proliferation and overcomes drug resistance in ovarian cancer","volume":"13","author":"Chen","year":"2022","journal-title":"Bioengineered"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"5744","DOI":"10.1073\/pnas.1110627109","article-title":"Ectodysplasin regulates hormone-independent mammary ductal morphogenesis via NF-\u03baB","volume":"109","author":"Voutilainen","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","first-page":"309","article-title":"NF-\u03baB, inflammation, immunity and cancer: Coming of age. Nature Reviews","volume":"18","author":"Taniguchi","year":"2018","journal-title":"Immunology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"264","DOI":"10.2174\/0929867321666141106124315","article-title":"Targeting the NF&#954;B Signaling Pathways for Breast Cancer Prevention and Therapy","volume":"22","author":"Wang","year":"2014","journal-title":"Curr. Med. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5520","DOI":"10.1158\/1078-0432.CCR-11-2904","article-title":"Molecular pathways: VCAM-1 as a potential therapeutic target in metastasis","volume":"18","author":"Chen","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_83","first-page":"545","article-title":"The non-canonical NF-\u03baB pathway in immunity and inflammation. Nature Reviews","volume":"17","author":"Sun","year":"2017","journal-title":"Immunology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.exphem.2016.03.010","article-title":"The NF-\u03baB family: Key players during embryonic development and HSC emergence","volume":"44","author":"Traver","year":"2016","journal-title":"Exp. Hematol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.ccr.2013.06.003","article-title":"Chromatin-Bound I\u039aBA regulates a subset of polycomb target genes in differentiation and cancer","volume":"24","author":"Mulero","year":"2013","journal-title":"Cancer Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1093\/molehr\/gap030","article-title":"Thrombin and interleukin-1 decrease HOX gene expression in human first trimester decidual cells: Implications for pregnancy loss","volume":"15","author":"Sarno","year":"2009","journal-title":"Mol. Hum. Reprod."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/nri3660","article-title":"Emergency granulopoiesis","volume":"14","author":"Manz","year":"2014","journal-title":"Nat. Reviews. Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5375","DOI":"10.4049\/jimmunol.1401909","article-title":"HOXA10 terminates emergency granulopoiesis by increasing expression of Triad1","volume":"194","author":"Wang","year":"2015","journal-title":"J. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1126\/science.aaa6204","article-title":"T cell exclusion, immune privilege, and the tumor microenvironment","volume":"348","author":"Joyce","year":"2015","journal-title":"Science"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1038\/icb.2016.13","article-title":"HOXB9 acts as a negative regulator of activated human T cells in response to amino acid deficiency","volume":"94","author":"Hayashi","year":"2016","journal-title":"Immunol. Cell Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e16207","DOI":"10.1111\/jog.16207","article-title":"Associations of Th1, Th2, Th17, and Treg cell levels and imbalance with recurrent spontaneous abortion: A meta-analysis","volume":"51","author":"Li","year":"2025","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13227-024-00231-5","article-title":"Comparative Hox genes expression within the dimorphic annelid Streblospio benedicti reveals patterning variation during development","volume":"15","author":"Harry","year":"2024","journal-title":"EvoDevo"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1002\/path.1710","article-title":"Pathophysiol. HOX Genes Their Role Cancer","volume":"205","author":"Grier","year":"2005","journal-title":"J. Pathol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1111\/febs.14476","article-title":"HOXC10 promotes proliferation and invasion and induces immunosuppressive gene expression in glioma","volume":"285","author":"Li","year":"2018","journal-title":"FEBS J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"6079","DOI":"10.1038\/onc.2015.53","article-title":"Repression of Hox genes by LMP1 in nasopharyngeal carcinoma and modulation of glycolytic pathway genes by HoxC8","volume":"34","author":"Jiang","year":"2015","journal-title":"Oncogene"},{"key":"ref_96","first-page":"2945","article-title":"HOXA10 Promotes the Development of Bladder Cancer through Regulating FOSL1","volume":"24","author":"Cui","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"581","DOI":"10.3892\/ol.2024.14714","article-title":"Circulating methylated HOXA9 tumor DNA as a biomarker for mortality in recurrent breast cancer: An exploratory study","volume":"28","author":"Bruun","year":"2024","journal-title":"Oncol. Lett."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Celik, O., Yurci, A., Ersahin, A., Gungor, N.D., Celik, N., Ozcil, M.D., Dogan, S., Dalkilic, S., Dalkilic, L., and Ulug, U. (2023). Endometrial Injury Upregulates Expression of Receptivity Genes in Women with Implantation Failure. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20053942"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Makrigiannakis, A., Makrygiannakis, F., and Vrekoussis, T. (2021). Approaches to improve endometrial receptivity in case of repeated implantation failures. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.613277"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.rbmo.2021.10.025","article-title":"The novel incorporation of aromatase inhibitor in hormonal replacement therapy cycles: A randomized controlled trial","volume":"44","author":"Elgindy","year":"2021","journal-title":"Reprod. BioMed. Online"},{"key":"ref_101","first-page":"270","article-title":"Aromatase Inhibitors for Endometriosis-Associated Infertility; Do we have sufficient evidence?","volume":"10","author":"Hashim","year":"2016","journal-title":"DOAJ"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.bbcan.2016.01.003","article-title":"HOX genes: Major actors in resistance to selective endocrine response modifiers","volume":"1865","author":"Jin","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA) Rev. Cancer"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Yuan, L., Wu, H., Huang, W., Bi, Y., Qin, A., and Yang, Y. (2021). The function of metformin in endometrial receptivity (ER) of patients with polycyclic ovary syndrome (PCOS): A systematic review and meta-analysis. Reprod. Biol. Endocrinol., 19.","DOI":"10.1186\/s12958-021-00772-7"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Shan, J., Li, D.-J., and Wang, X.-Q. (2023). Towards a Better Understanding of Endometriosis-Related Infertility: A review on how Endometriosis affects endometrial receptivity. Biomolecules, 13.","DOI":"10.3390\/biom13030430"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.7150\/ijbs.58657","article-title":"Protopanaxadiol improves endometriosis associated infertility and miscarriage in sex hormones receptors-dependent and independent manners","volume":"17","author":"Lai","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"eabk1003","DOI":"10.1126\/sciadv.abk1003","article-title":"Dissecting the evolutionary role of the Hox gene proboscipedia in Drosophila mouthpart diversification by full locus replacement","volume":"7","author":"Auradkar","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/s13287-023-03387-4","article-title":"Endometrium-derived mesenchymal stem cells suppress progression of endometrial cancer via the DKK1-Wnt\/\u03b2-catenin signaling pathway","volume":"14","author":"Xu","year":"2023","journal-title":"Stem Cell Res. Ther."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/rmb2.12339","article-title":"Mesenchymal stem cells for restoring endometrial function: An infertility perspective","volume":"20","author":"Rungsiwiwut","year":"2020","journal-title":"Reprod. Med. Biol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/mrd.23476","article-title":"Adult stem cells in endometrial regeneration: Molecular insights and clinical applications","volume":"88","author":"Lv","year":"2021","journal-title":"Mol. Reprod. Dev."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Martinovi\u0107, L.S., Mladeni\u0107, T., Lovri\u0107, D., Ostoji\u0107, S., and Pavli\u0107, S.D. (2024). Decoding the epigenetics of infertility: Mechanisms, environmental influences, and therapeutic strategies. Epigenomes, 8.","DOI":"10.3390\/epigenomes8030034"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1016\/j.ymthe.2022.01.036","article-title":"Increased expression of HOXA11-AS attenuates endometrial decidualization in recurrent implantation failure patients","volume":"30","author":"Zhao","year":"2022","journal-title":"Mol. Ther."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/4\/563\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:12:26Z","timestamp":1760029946000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/4\/563"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,10]]},"references-count":111,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["biom15040563"],"URL":"https:\/\/doi.org\/10.3390\/biom15040563","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,10]]}}}