{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:09:53Z","timestamp":1785413393211,"version":"3.56.0"},"reference-count":50,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background: Miscarriage is defined as the spontaneous loss of a pregnancy before fetal viability and includes all pregnancy losses occurring from conception until 24 weeks of gestation. Recurrent pregnancy loss (RPL) is traditionally defined as three or more consecutive miscarriages. Emerging evidence suggests that both miR-99a and miR-143 may serve as promising biomarkers for recurrent pregnancy loss. Methods: A total of 42 women of reproductive age (18\u201345 years) were enrolled in this study. The control group consisted of 13 women with no history of recurrent miscarriage, whereas the study group included 29 women diagnosed with spontaneous miscarriages\/recurrent implantation failure. Results: Both miR-99a and miR-143 showed significantly lower relative expression in women with recurrent miscarriage\/recurrent implantation failure compared with the control group. Conclusions: Despite the relatively small sample size, statistically significant differences in the expression of miR-99a and miR-143 were observed between the case and control groups, with lower relative expression of both miRNAs in the case group. These findings suggest that both microRNAs may be associated with molecular pathways involved in reproductive failure. Furthermore, investigating the expression patterns of miR-99a and miR-143 may contribute to a better understanding of the molecular mechanisms underlying recurrent miscarriage\/recurrent implantation failure. Such insights may facilitate the development of genetic risk profiles for women with unexplained pregnancy loss and implantation failure, as well as support the identification of potential therapeutic targets. Further studies are required to determine their potential value as molecular markers and to clarify their functional relevance in reproductive failure.<\/jats:p>","DOI":"10.3390\/jcm15155955","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:38:54Z","timestamp":1785411534000},"page":"5955","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Expression Levels of miR-99a and miR-143 in Women Diagnosed with Recurrent Pregnancy Loss"],"prefix":"10.3390","volume":"15","author":[{"given":"Konstantina","family":"Kouvoutsaki","sequence":"first","affiliation":[{"name":"Reproductive Biology Laboratory, First Department of Obstetrics and Gynecology, Alexandra Hospital, Medical School, National and Kapodistrian University of Athens, 10559 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Nazou","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, 10559 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Despoina","family":"Mavrogianni","sequence":"additional","affiliation":[{"name":"Reproductive Biology Laboratory, First Department of Obstetrics and Gynecology, Alexandra Hospital, Medical School, National and Kapodistrian University of Athens, 10559 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanouela","family":"Liokari","sequence":"additional","affiliation":[{"name":"Fertility Institute Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismini","family":"Anagnostaki","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, 10559 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Tzeli","sequence":"additional","affiliation":[{"name":"Department of Midwifery, Faculty of Health and Caring Sciences, University of West Attica, 12243 Egaleo, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1254-1984","authenticated-orcid":false,"given":"Ioannis","family":"Arkoulis","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, 10559 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofoklis","family":"Stavros","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, 10559 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandros","family":"Rodolakis","sequence":"additional","affiliation":[{"name":"First Department of Obstetrics and Gynecology, Alexandra Hospital, Medical School, National and Kapodistrian University of Athens, 10559 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Drakakis","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, 10559 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterini","family":"Domali","sequence":"additional","affiliation":[{"name":"First Department of Obstetrics and Gynecology, Alexandra Hospital, Medical School, National and Kapodistrian University of Athens, 10559 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"ref_1","unstructured":"Kline, J., Stein, Z., and Susser, M. (1989). Monographs in Epidemiology and Biostatistics. Conception to Birth: Epidemiology of Prenatal Development, Oxford University Press. [1st ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1093\/humrep\/17.2.446","article-title":"Cytogenetic Analysis of Miscarriages from Couples with Recurrent Miscarriage: A Case-Control Study","volume":"17","author":"Stephenson","year":"2002","journal-title":"Hum. Reprod."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1111\/ajo.13821","article-title":"Australasian Recurrent Pregnancy Loss Clinical Management Guideline 2024 Part I","volume":"64","author":"Suker","year":"2024","journal-title":"Aust. N. Z. J. Obstet. Gynaecol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1007\/s00404-024-07604-0","article-title":"Obstetric and perinatal outcomes of women with a history of recurrent pregnancy loss: A meta-analysis of cohort studies","volume":"310","author":"Liu","year":"2024","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/hdy.2015.84","article-title":"Microguards and Micromessengers of the Genome","volume":"116","author":"Green","year":"2016","journal-title":"Heredity"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"O\u2019Brien, J., Hayder, H., Zayed, Y., and Peng, C. (2018). Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front. Endocrinol., 9.","DOI":"10.3389\/fendo.2018.00402"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S163","DOI":"10.1016\/j.ajog.2015.05.057","article-title":"MicroRNAs in Placental Health and Disease","volume":"213","author":"Mouillet","year":"2015","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.placenta.2012.05.009","article-title":"MicroRNA Expression Profiles of Trophoblastic Cells","volume":"33","author":"Chaiwangyen","year":"2012","journal-title":"Placenta"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1007\/s12032-014-0934-3","article-title":"MiR-99a and -99b Inhibit Cervical Cancer Cell Proliferation and Invasion by Targeting MTOR Signaling Pathway","volume":"31","author":"Wang","year":"2014","journal-title":"Med. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1002\/jcb.24965","article-title":"MiR-99a Suppresses the Metastasis of Human Non-Small Cell Lung Cancer Cells by Targeting AKT1 Signaling Pathway","volume":"116","author":"Yu","year":"2015","journal-title":"J. Cell. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Feng, Y., Kang, Y., He, Y., Liu, J., Liang, B., Yang, P., and Yu, Z. (2014). MicroRNA-99a Acts as a Tumor Suppressor and Is down-Regulated in Bladder Cancer. BMC Urol., 14.","DOI":"10.1186\/1471-2490-14-50"},{"key":"ref_12","first-page":"387","article-title":"MicroRNA Regulation of the Expression of the Estrogen Receptor in Endometrial Cancer","volume":"3","author":"Zhou","year":"2010","journal-title":"Mol. Med. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"363","DOI":"10.4048\/jbc.2018.21.e56","article-title":"Identification and Validation of Circulating MicroRNA Signatures for Breast Cancer Early Detection Based on Large Scale Tissue-Derived Data","volume":"21","author":"Yu","year":"2018","journal-title":"J. Breast Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/j.1365-2052.2009.02015.x","article-title":"Identification of Target Genes and Pathways Associated with Chicken MicroRNA MiR-143","volume":"41","author":"Trakooljul","year":"2010","journal-title":"Anim. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/nature08195","article-title":"MiR-145 and MiR-143 Regulate Smooth Muscle Cell Fate and Plasticity","volume":"460","author":"Cordes","year":"2009","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1254\/jphs.10R12FM","article-title":"MicroRNAs and Their Therapeutic Potential for Human Diseases: MicroRNAs, MiR-143 and -145, Function as Anti-Oncomirs and the Application of Chemically Modified Mir-143 as an Anti-Cancer Drug","volume":"114","author":"Kitade","year":"2010","journal-title":"J. Pharmacol. Sci."},{"key":"ref_17","first-page":"1363","article-title":"MicroRNA-143, down-Regulated in Osteosarcoma, Promotes Apoptosis and Suppresses Tumorigenicity by Targeting Bcl-2","volume":"24","author":"Zhang","year":"2010","journal-title":"Oncol. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10495","DOI":"10.1038\/s41598-018-28872-2","article-title":"Multipronged Activity of Combinatorial MiR-143 and MiR-506 Inhibits Lung Cancer Cell Cycle Progression and Angiogenesis in Vitro","volume":"8","author":"Hossian","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/S0140-6736(06)69204-0","article-title":"Recurrent Miscarriage","volume":"368","author":"Rai","year":"2006","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Li, Q., Chen, S., Dong, X., Fu, S., Zhang, T., Zheng, W., Tian, Y., and Huang, D. (2023). The Progress of Research on Genetic Factors of Recurrent Pregnancy Loss. Genet. Res.","DOI":"10.1155\/2023\/9164374"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1093\/humrep\/deg309","article-title":"Embryoscopic and Cytogenetic Analysis of 233 Missed Abortions: Factors Involved in the Pathogenesis of Developmental Defects of Early Failed Pregnancies","volume":"18","author":"Philipp","year":"2003","journal-title":"Hum. Reprod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1530\/eje.0.1500751","article-title":"Thyroid Autoimmunity and Miscarriage","volume":"150","author":"Prummel","year":"2004","journal-title":"Eur. J. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/S0140-6736(96)04125-6","article-title":"Increased Fetal Loss in Women with Heritable Thrombophilia","volume":"348","author":"Preston","year":"1996","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1016\/S0140-6736(21)00682-6","article-title":"Miscarriage matters: The epidemiological, physical, psychological, and economic costs of early pregnancy loss","volume":"397","author":"Quenby","year":"2021","journal-title":"Lancet"},{"key":"ref_25","first-page":"24","article-title":"Evidence-Based Update: Immunological Evaluation of Recurrent Implantation Failure","volume":"1","author":"Segovia","year":"2016","journal-title":"Reprod. Immunol. Open Access"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1590\/S1807-59322011000400026","article-title":"An Update on the Clinical Assessment of the Infertile Male","volume":"66","author":"Esteves","year":"2011","journal-title":"Clinics"},{"key":"ref_27","first-page":"8067972","article-title":"The Role of MiRNAs as Biomarkers for Pregnancy Outcomes: A Comprehensive Review","volume":"2017","author":"Barchitta","year":"2017","journal-title":"Int. J. Genom."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Chen, D., and Wang, W. (2013). Human Placental MicroRNAs and Preeclampsia1. Biol. Reprod., 88.","DOI":"10.1095\/biolreprod.113.107805"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5519","DOI":"10.3390\/ijms14035519","article-title":"MicroRNAs in Human Placental Development and Pregnancy Complications","volume":"14","author":"Fu","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/S1472-6483(10)61781-6","article-title":"Human Embryo Implantation: Current Knowledge and Clinical Implications in Assisted Reproductive Technology","volume":"9","author":"Hoozemans","year":"2004","journal-title":"Reprod. Biomed. Online"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s10815-018-1335-x","article-title":"MiRNA-99a Can Regulate Proliferation and Apoptosis of Human Granulosa Cells via Targeting IGF-1R in Polycystic Ovary Syndrome","volume":"36","author":"Geng","year":"2019","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_32","first-page":"4593","article-title":"Expression of TGF-\u03921 and MiR-99a in Serum of Patients with Early Spontaneous Abortion and Correlation with Hormone Levels during Pregnancy","volume":"17","author":"Xie","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1210\/me.2008-0387","article-title":"MicroRNA-Regulated Pathways Associated with Endometriosis","volume":"23","author":"Teague","year":"2009","journal-title":"Mol. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.1093\/humrep\/der255","article-title":"MicroRNAs Are Associated with Human Embryo Implantation Defects","volume":"26","author":"Revel","year":"2011","journal-title":"Hum. Reprod."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wang, Y., Zheng, X., Luo, D., Xu, W., and Zhou, X. (2022). MiR-99a Alleviates Apoptosis and Extracellular Matrix Degradation in Experimentally Induced Spine Osteoarthritis by Targeting FZD8. BMC Musculoskelet. Disord., 23.","DOI":"10.1186\/s12891-022-05822-8"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"201514","DOI":"10.1155\/2014\/201514","article-title":"Leukemia Inhibitory Factor: Roles in Embryo Implantation and in Nonhormonal Contraception","volume":"2014","author":"Salleh","year":"2014","journal-title":"Sci. World J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"221.e1","DOI":"10.1016\/j.ajog.2013.12.043","article-title":"Distinct Cervical MicroRNA Profiles Are Present in Women Destined to Have a Preterm Birth","volume":"210","author":"Elovitz","year":"2014","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3273","DOI":"10.3892\/mmr.2016.4892","article-title":"Decreased MiR-143 and Increased MiR-21 Placental Expression Levels Are Associated with Macrosomia","volume":"13","author":"Zhang","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3892\/ijmm.2014.1989","article-title":"Differential Expression of Circulating MiRNAs in Maternal Plasma in Pregnancies with Fetal Macrosomia","volume":"35","author":"Ge","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"ref_40","unstructured":"Shi, H., Shen, H., Xu, J., Zhao, S., Yao, S.Z., and Jiang, N. (2018). MiR-143-3p Suppresses the Progression of Ovarian Cancer. Am. J. Transl. Res., 10."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.fertnstert.2016.04.013","article-title":"Serum MicroRNAs as Diagnostic Markers of Endometriosis: A Comprehensive Array-Based Analysis","volume":"106","author":"Cosar","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"369549","DOI":"10.1155\/2010\/369549","article-title":"Differential Expression of Micrornas between Eutopic and Ectopic Endometrium in Ovarian Endometriosis","volume":"2010","author":"Filigheddu","year":"2010","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.bbagen.2014.11.023","article-title":"MiR-143 and Rat Embryo Implantation","volume":"1850","author":"Tian","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"114603","DOI":"10.1016\/j.taap.2019.114603","article-title":"Suppression of MiR-143 Contributes to Overexpression of IL-6, HIF-1\u03b1 and NF-\u039aB P65 in Cr(VI)-Induced Human Exposure and Tumor Growth","volume":"378","author":"Wang","year":"2019","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1093\/ntr\/ntp144","article-title":"Interaction between Smoking and the Interleukin-6 Gene Affects Systemic Levels of Inflammatory Biomarkers","volume":"11","author":"Sunyer","year":"2009","journal-title":"Nicotine Tob. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1037\/hea0000775","article-title":"Interleukin-6 and Body Mass Index, Tobacco Use, and Sleep in Gynecologic Cancers","volume":"38","author":"Kacel","year":"2019","journal-title":"Health Psychol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s11357-011-9244-2","article-title":"Effects of Aging and Menopause on Serum Interleukin-6 Levels and Peripheral Blood Mononuclear Cell Cytokine Production in Healthy Nonobese Women","volume":"34","author":"Kim","year":"2012","journal-title":"Age"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1161\/01.RES.0000115557.25127.8D","article-title":"Interleukin-6 Induces Oxidative Stress and Endothelial Dysfunction by Overexpression of the Angiotensin II Type 1 Receptor","volume":"94","author":"Wassmann","year":"2004","journal-title":"Circ. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s10735-024-10332-z","article-title":"Oxidative Stress and Its Role in Recurrent Pregnancy Loss: Mechanisms and Implications","volume":"56","author":"Zhang","year":"2024","journal-title":"J. Mol. Histol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1007\/s12033-022-00496-y","article-title":"MiR-99a-5p Constrains Epithelial\u2013Mesenchymal Transition of Cervical Squamous Cell Carcinoma Via Targeting CDC25A\/IL6","volume":"64","author":"Gu","year":"2022","journal-title":"Mol. Biotechnol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/15\/5955\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:52:57Z","timestamp":1785412377000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/15\/5955"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":50,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["jcm15155955"],"URL":"https:\/\/doi.org\/10.3390\/jcm15155955","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]}}}