{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T19:28:24Z","timestamp":1784230104885,"version":"3.55.0"},"reference-count":45,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T00:00:00Z","timestamp":1677110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Background: Homeobox genes A10 (HOXA10) and A11 (HOXA11), members of the abdominal B gene family, are responsible for embryonic survival and implantation. This study was planned to investigate whether endometrial injury alters the expression of both transcripts in women with implantation failure. Methods: A total of 54 women with implantation failure were divided into two equal groups as experimental (scratching) and sham (no scratching). Participants in the scratching group were exposed to endometrial injury in the mid-luteal phase, and those in the sham group were exposed to endometrial flushing. The scratching group, but not the sham group, underwent prior endometrial sampling. A second endometrial sampling was performed on the scratching group in the mid-luteal phase of the following cycle. The mRNA and protein levels of the HOXA10 and 11 transcripts were determined in endometrial samples collected before and after injury\/flushing. Participants in each group underwent IVF\/ET in the cycle after the second endometrial sampling. Results: Endometrial injury caused a 60.1-fold (p &lt; 0.01) increase in HOXA10 mRNA and a 9.0-fold increase in HOXA11 mRNA (p &lt; 0.02). Injury resulted in a significant increase in both HOXA10 (p &lt; 0.001) and HOXA11 protein expression (p &lt; 0.003). There was no significant change in HOXA10 and 11 mRNA expressions after flushing. Clinical pregnancy, live birth, and miscarriage rates of the both groups were similar. Conclusions: Endometrial injury increases homeobox transcript expression at both mRNA and protein levels.<\/jats:p>","DOI":"10.3390\/ijerph20053942","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T02:28:57Z","timestamp":1677119337000},"page":"3942","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Endometrial Injury Upregulates Expression of Receptivity Genes in Women with Implantation Failure"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8994-796X","authenticated-orcid":false,"given":"Onder","family":"Celik","sequence":"first","affiliation":[{"name":"Private Clinic Obstetrics and Gynecology, 64000 Usak, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4808-9019","authenticated-orcid":false,"given":"Arzu","family":"Yurci","sequence":"additional","affiliation":[{"name":"In Vitro Fertilization (IVF), Andrology and Genetics Center, Memorial Bahcelievler Hospital, 34180 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aynur","family":"Ersahin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Bahcesehir University Goztepe Medicalpark Hospital, 34732 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7234-3876","authenticated-orcid":false,"given":"Nur D.","family":"Gungor","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Bahcesehir University Goztepe Medicalpark Hospital, 34732 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilufer","family":"Celik","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Behcet Uz Children\u2019s Hospital, 35210 Izmir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa D.","family":"Ozcil","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Mustafa Kemal University, 31060 Hatay, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serdar","family":"Dogan","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Mustafa Kemal University, 31060 Hatay, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Semih","family":"Dalkilic","sequence":"additional","affiliation":[{"name":"Molecular Biology and Genetics Program, Department of Biology, Faculty of Science, Firat University, 23000 Elazig, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutfiye","family":"Dalkilic","sequence":"additional","affiliation":[{"name":"Molecular Biology and Genetics Program, Department of Biology, Faculty of Science, Firat University, 23000 Elazig, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4718-6020","authenticated-orcid":false,"given":"Ulun","family":"Ulug","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, Halic University, 34060 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudenaz","family":"Celik","sequence":"additional","affiliation":[{"name":"Medical Faculty, Sofia University \u201cSt. Kliment Ohridski\u201d, 1407 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8426-8490","authenticated-orcid":false,"given":"Andrea","family":"Tinelli","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, CERICSAL (Centro di RIcerca Clinica SALentino), \u201cVeris Delli Ponti Hospital\u201d, 73020 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.rbmo.2013.08.011","article-title":"Recurrent implantation failure: Definition and management","volume":"28","author":"Coughlan","year":"2014","journal-title":"Reprod. Biomed. Online"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1016\/j.fertnstert.2021.09.014","article-title":"A review of the pathophysiology of recurrent implantation failure","volume":"116","author":"Franasiak","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1007\/s10815-012-9861-4","article-title":"Assessment and treatment of repeated implantation failure (RIF)","volume":"29","author":"Simon","year":"2012","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/S0015-0282(99)00531-2","article-title":"Temporal analysis of connexin43, protein and gene expression, throughout the menstrual cycle in human endometrium","volume":"73","author":"Granot","year":"2000","journal-title":"Fertil. Steril."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1016\/S0015-0282(03)00345-5","article-title":"Local injury to the endometrium doubles the incidence of successful pregnancies in patients undergoing in vitro fertilization","volume":"6","author":"Barash","year":"2003","journal-title":"Fertil. Steril."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1111\/j.1447-0756.2012.02016.x","article-title":"Endometrial scratching to improve pregnancy rate in couples with unexplained subfertility: A randomized controlled trial","volume":"39","author":"Gibreel","year":"2013","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1080\/09513590.2016.1255325","article-title":"Endometrial injury for RIF patients undergoing IVF\/ICSI: A prospective nonrandomized controlled trial","volume":"33","author":"Siristatidis","year":"2017","journal-title":"Gynecol. Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"933","DOI":"10.3109\/09513590.2011.650750","article-title":"Does local injury to the endometrium before IVF cycle really affect treatment outcome? Results of a randomized placebo-controlled trial","volume":"28","author":"Baum","year":"2012","journal-title":"Gynecol. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s12958-021-00877-z","article-title":"Endometrial injury concurrent with hysteroscopy increases the expression of Leukemia inhibitory factor: A preliminary study","volume":"20","author":"Ersahin","year":"2022","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1055\/s-0034-1375182","article-title":"Remedies for recurrent implantation failure","volume":"32","author":"Zeyneloglu","year":"2014","journal-title":"Semin. Reprod. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1016\/j.fertnstert.2010.02.022","article-title":"Local injury of the endometrium induces an inflammatory response that promotes successful implantation","volume":"94","author":"Gnainsky","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1016\/j.fertnstert.2007.05.064","article-title":"Local injury to the endometrium in controlled ovarian hyperstimulation cycles improves implantation rates","volume":"89","author":"Zhou","year":"2008","journal-title":"Fertil. Steril."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.fertnstert.2008.01.043","article-title":"Endometrial biopsy-induced gene modulation: First evidence for the expression of bladder-transmembranal uroplakin Ib in human endometrium","volume":"91","author":"Kalma","year":"2009","journal-title":"Fertil. Steril."},{"key":"ref_14","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_15","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/374460a0","article-title":"Sexually dimorphic sterility phenotypes in Hoxa10-deficient mice","volume":"374","author":"Satokata","year":"1995","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1242\/dev.122.9.2687","article-title":"Mechanisms of reduced fertility in Hoxa-10 mutant mice: Uterine homeosis and loss of maternal Hoxa-10 expression","volume":"122","author":"Benson","year":"1996","journal-title":"Development"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.rbmo.2013.12.006","article-title":"What exactly do we mean by 'recurrent implantation failure'? A systematic review and opinion","volume":"28","author":"Polanski","year":"2014","journal-title":"Reprod. Biomed. Online"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s12958-017-0296-8","article-title":"Effect of local endometrial injury in proliferative vs. luteal phase on IVF outcomes in unselected sub fertile women undergoing in vitro fertilization","volume":"15","author":"Liu","year":"2017","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_19","unstructured":"World Health Organization (1993). International Statistical Classification of Diseases and Related Health Problems, World Health Organization."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.rbmo.2010.06.039","article-title":"Endometrial implantation factors in women with submucous uterine fibroids","volume":"21","author":"Miell","year":"2010","journal-title":"Reprod. Biomed. Online"},{"key":"ref_21","first-page":"CD009517","article-title":"Endometrial injury in women undergoing assisted reproductive techniques","volume":"3","author":"Nastri","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1111\/j.1479-828X.2009.01076.x","article-title":"Endometrial local injury improves the pregnancy rate among recurrent implantation failure patients undergoing in vitro fertilisation\/intra cytoplasmic sperm injection: A randomised clinical trial","volume":"49","author":"Karimzadeh","year":"2009","journal-title":"Aust. N. Z. J. Obstet. Gynaecol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/ijgo.12355","article-title":"Randomized controlled trial of the effect of endometrial injury on implantation and clinical pregnancy rates during the first ICSI cycle","volume":"2","author":"Maged","year":"2018","journal-title":"Int. J. Gynecol. Obstet."},{"key":"ref_24","first-page":"419","article-title":"Endometrial injury for women with previous in vitro fertilization failure\u2014Does it improve pregnancy rate?","volume":"6","author":"Zygula","year":"2016","journal-title":"Neuroendocrinol. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ejogrb.2015.06.026","article-title":"Endometrial injury prior to assisted reproductive techniques for recurrent implantation failure: A systematic literature review","volume":"193","author":"Panagiotopoulou","year":"2015","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_26","first-page":"hoy025","article-title":"Endometrial scratching prior to IVF; does it help and for whom? A systematic review and meta-analysis","volume":"2019","author":"Kasius","year":"2019","journal-title":"Hum. Reprod. Open"},{"key":"ref_27","first-page":"563","article-title":"Ueber die experimentelle Erzeugung von Knoten von Deciduage webe in dem Uterus des Meerschweinchensnachstattgefunder copulation","volume":"18","author":"Loeb","year":"1907","journal-title":"Zbtf\u00fcr Allg Path Path Anat"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1071\/BI9690689","article-title":"Interactions between oestradiol 3, 17 beta and progesterone on the induction and growth of deciduomata in ovariectomized mice","volume":"22","author":"Humphrey","year":"1969","journal-title":"Aust. J. Biol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1095\/biolreprod29.4.833","article-title":"Effect of histamine receptor antagonists and indomethacin on implantation in the rabbit","volume":"29","author":"Hoos","year":"1983","journal-title":"Biol. Reprod."},{"key":"ref_30","first-page":"CD009517","article-title":"Endometrial injury in women undergoing in vitro fertilisation (IVF)","volume":"6","author":"Lensen","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.fertnstert.2015.04.041","article-title":"Laparoscopic endometrioma resection increases peri-implantation endometrial HOXA-10 and HOXA-11 mRNA expression","volume":"104","author":"Celik","year":"2015","journal-title":"Fertil. Steril."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1055\/s-2000-13478","article-title":"The role of HOX genes in the development and function of the female reproductive tract","volume":"18","author":"Taylor","year":"2000","journal-title":"Semin. Reprod. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1210\/mend.13.6.0284","article-title":"Hoxa-10 regulates uterine stromal cell responsiveness to progesterone during implantation and decidualization in the mouse","volume":"13","author":"Lim","year":"1999","journal-title":"Mol. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"S162","DOI":"10.1016\/j.fertnstert.2008.07.374","article-title":"Local injury of the proliferative phase endometrium substantially increases the ER expression in following secretory phase endometrium","volume":"90","author":"Li","year":"2008","journal-title":"Fertil. Steril."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1097\/GCO.0b013e32832a0654","article-title":"Local injury to the endometrium: Its effect on implantation","volume":"21","author":"Li","year":"2009","journal-title":"Curr. Opin. Obstet. Gynecol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0015-0282(97)80080-5","article-title":"Endometrial evaluation by aspiration biopsy on the day of oocyte retrieval in the embryo transfer cycles in patients with serum progesterone rise during the follicular phase","volume":"67","author":"Ubaldi","year":"1997","journal-title":"Fertil. Steril."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1177\/1933719116654993","article-title":"Surgery for Benign Gynecological Disorders Improve Endometrium Receptivity","volume":"24","author":"Celik","year":"2017","journal-title":"Reprod. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.fertnstert.2006.06.041","article-title":"Salpingectomy increases peri-implantation endometrial HOXA10 expression in women with hydrosalpinx","volume":"87","author":"Daftary","year":"2007","journal-title":"Fertil. Steril."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1007\/s43032-019-00072-x","article-title":"Laparoscopic Ovarian Drilling Improves Endometrial Homeobox Gene Expression in PCOS","volume":"27","author":"Senturk","year":"2020","journal-title":"Reprod. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1038\/2006","article-title":"Defective production of both leukemia inhibitory factor and type 2 T-helper cytokines by decidual T cells in unexplained recurrent abortions","volume":"4","author":"Piccinni","year":"1998","journal-title":"Nat. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/j.1600-0897.1998.tb00346.x","article-title":"Leukemia inhibitory factor in human reproduction","volume":"39","author":"Senturk","year":"1998","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1006\/dbio.1999.9528","article-title":"Targeted disruption of Hoxd9 and Hoxd10 alters locomotor behavior, vertebral identity, and peripheral nervous system development","volume":"216","author":"Spyropoulos","year":"1999","journal-title":"Dev. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.ejogrb.2020.08.036","article-title":"Genome-wide expression analysis of endometrium before and after endometrioma surgery","volume":"253","author":"Celik","year":"2020","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1016\/j.fertnstert.2006.12.057","article-title":"Does the timing of mock embryo transfer affect in vitro fertilization implantation and pregnancy rates?","volume":"88","author":"Katariya","year":"2007","journal-title":"Fertil. Steril."},{"key":"ref_45","first-page":"951","article-title":"Outcome of mock embryo transfer before the first IVF cycle: A randomized control trial","volume":"18","author":"Borkar","year":"2020","journal-title":"Int. J. Reprod. Biomed."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/20\/5\/3942\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:39:55Z","timestamp":1760121595000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/20\/5\/3942"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,23]]},"references-count":45,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijerph20053942"],"URL":"https:\/\/doi.org\/10.3390\/ijerph20053942","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,23]]}}}