{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T10:05:50Z","timestamp":1779876350039,"version":"3.53.1"},"update-to":[{"DOI":"10.12688\/f1000research.166306.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000}}],"reference-count":22,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>\n                    Background Recurrent spontaneous abortion (RSA) is one of the most common reproductive complications among women of childbearing age. Several factors\u2014including genetic, anatomical, endocrine, infectious, environmental, and immunological causes\u2014have been implicated in RSA. This study aimed to explore the potential association between RSA and the expression patterns of selected genes involved in critical biological processes related to pregnancy maintenance and miscarriage. Methods The relative expression levels of\n                    <ns3:italic>matrix metallopeptidase 2 (MMP2)<\/ns3:italic>\n                    ,\n                    <ns3:italic>matrix metallopeptidase 9 (MMP9)<\/ns3:italic>\n                    ,\n                    <ns3:italic>DNA methyltransferase 1 (DNMT1)<\/ns3:italic>\n                    ,\n                    <ns3:italic>DNA methyltransferase 3 alpha (DNMT3A)<\/ns3:italic>\n                    , and\n                    <ns3:italic>methylenetetrahydrofolate reductase (MTHFR)<\/ns3:italic>\n                    were evaluated using peripheral blood samples from 30 women with a history of two or more spontaneous abortions (cases) and 30 age-matched non-pregnant women with no history of miscarriage and at least one successful pregnancy (controls). Results No significant differences in the mRNA expression levels of the target genes were observed between women with RSA and the control group. Conclusions Our findings suggest that peripheral blood gene expression profiles of\n                    <ns3:italic>MMP2, MMP9, DNMT1, DNMT3A<\/ns3:italic>\n                    , and\n                    <ns3:italic>MTHFR<\/ns3:italic>\n                    may not adequately reflect tissue-specific changes associated with RSA. Further investigations using relevant tissues, such as placental or decidual samples, are warranted to better understand the molecular mechanisms underlying RSA.\n                  <\/ns3:p>","DOI":"10.12688\/f1000research.166306.2","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T14:45:07Z","timestamp":1759761907000},"page":"763","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Peripheral Blood Expression of MMPs and DNA Methylation-Related Genes in Women with Recurrent Spontaneous Abortion: A Case-Control Study"],"prefix":"10.12688","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4311-8810","authenticated-orcid":false,"given":"Maryam","family":"Imani","sequence":"first","affiliation":[{"name":"Yazd Reproductive Immunology Research Center, Shahid Sadoughi University of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fateme","family":"Zare","sequence":"additional","affiliation":[{"name":"Yazd Reproductive Immunology Research Center, Shahid Sadoughi University of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Hadinedoushan","sequence":"additional","affiliation":[{"name":"Yazd Reproductive Immunology Research Center, Shahid Sadoughi University of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fateme","family":"Rahmani","sequence":"additional","affiliation":[{"name":"Yazd Department of Immunology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3743-4449","authenticated-orcid":false,"given":"Farzaneh","family":"Fesahat","sequence":"additional","affiliation":[{"name":"Yazd Reproductive Immunology Research Center, Shahid Sadoughi University of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2025,10,6]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"302-315","DOI":"10.26502\/fjwhd.2644-28840038","article-title":"Recurrent pregnancy loss (RPL): an overview.","volume":"3","author":"S Sultana","year":"2020","journal-title":"J. Womens Health Dev."},{"key":"ref2","first-page":"570-589","article-title":"Understanding recurrent pregnancy loss: recent advances on its etiology, clinical diagnosis, and management.","volume":"2","author":"C Cao","year":"2023","journal-title":"J. Medical Review."},{"key":"ref3","first-page":"34","article-title":"Genetics of recurrent miscarriage: challenges, current knowledge, future directions.","volume":"3","author":"K Rull","year":"2012","journal-title":"J. Front. Genet."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"355-366","DOI":"10.1007\/s10815-017-1108-y","article-title":"Genetic and epigenetic variations associated with idiopathic recurrent pregnancy loss.","volume":"35","author":"L Arias-Sosa","year":"2018","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref5","doi-asserted-by":"crossref","first-page":"199","DOI":"10.29252\/ijrm.14.3.199","article-title":"Relationship between sperm protamine deficiency and apoptosis in couples with unexplained repeated spontaneous abortions.","volume":"14","author":"A Talebi","year":"2016","journal-title":"Int. J. Reprod. BioMed."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"738962","DOI":"10.3389\/fimmu.2021.738962","article-title":"DNA methylation and recurrent pregnancy loss: a mysterious compass?","volume":"12","author":"Q Zhou","year":"2021","journal-title":"Front. Immunol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e12741","DOI":"10.1111\/aji.12741","article-title":"Cortisol inhibits CSF 2 and CSF 3 via DNA methylation and inhibits invasion in first-trimester trophoblast cells.","volume":"78","author":"A Smith","year":"2017","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"547-554","DOI":"10.1093\/molehr\/gan046","article-title":"Specific tumour-associated methylation in normal human term placenta and first-trimester cytotrophoblasts.","volume":"14","author":"B Novakovic","year":"2008","journal-title":"Mol. Hum. Reprod."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"738962","DOI":"10.3389\/fimmu.2021.738962","article-title":"DNA methylation and recurrent pregnancy loss: a mysterious compass?","volume":"12","author":"Q Zhou","year":"2021","journal-title":"Front. Immunol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s13148-023-01432-w","article-title":"DNA methylation abnormalities induced by advanced maternal age in villi prime a high-risk state for spontaneous abortion.","volume":"15","author":"M Qin","year":"2023","journal-title":"Clin. Epigenetics."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"379-382","DOI":"10.1134\/S1022795420030023","article-title":"DNMT1 And DNMT3a gene polymorphisms and early pregnancy loss.","volume":"56","author":"A Ahmed","year":"2020","journal-title":"Russ. J. Genet."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"883-889","DOI":"10.3892\/mmr.2012.763","article-title":"DNA methylation in the human placenta and fetal growth.","volume":"5","author":"O Koukoura","year":"2012","journal-title":"Mol. Med. Rep."},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1-9","DOI":"10.1186\/s43141-021-00147-w","article-title":"Correlation of methylation status in MTHFR promoter region with recurrent pregnancy loss.","volume":"19","author":"M Shaker","year":"2021","journal-title":"J. Genet. Eng. Biotechnol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"145173","DOI":"10.1016\/j.gene.2020.145173","article-title":"Association of MMP2 and MMP9 gene polymorphisms with the recurrent spontaneous abortion: A meta-analysis.","volume":"767","author":"Y Yan","year":"2021","journal-title":"Gene."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"945-949","DOI":"10.1007\/s10815-017-0939-x","article-title":"Genetic variation in matrix metalloproteinase MMP2 and MMP9 as a risk factor for idiopathic recurrent spontaneous abortions in an Indian population.","volume":"34","author":"D Ramu","year":"2017","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref15","article-title":"WMA - The World Medical Association-Declaraci\u00f3n de Helsinki de la AMM \u2013 Principios \u00e9ticos para las investigaciones m\u00e9dicas en seres humanos.","year":"citado 30 de noviembre de 2023"},{"key":"ref16","first-page":"351-356","article-title":"DNA hypomethylation in villi of patients with unexplained recurrent spontaneous abortion and its mechanism.","volume":"35","author":"J Li","year":"2019","journal-title":"Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi."},{"key":"ref17","first-page":"1-10","article-title":"Insufficient maintenance DNA methylation is associated with abnormal embryonic development.","volume":"10","author":"L Yin","year":"2012","journal-title":"BMC Med."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"430-440","DOI":"10.30476\/IJMS.2023.99555.3162","article-title":"Association between Methylenetetrahydrofolate Reductase (MTHFR) and 5-Methyltetrahydrofolate-Homocysteine Methyltransferase Reductase (MTRR) Polymorphisms in Iraqi Patients with COVID-19.","volume":"49","author":"S Alsaffar","year":"2024","journal-title":"Iran J. Med. Sci."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"68-73","DOI":"10.1016\/j.gene.2019.04.036","article-title":"Differential global and MTHFR gene specific methylation patterns in preeclampsia and recurrent miscarriages: A case-control study from North India.","volume":"704","author":"J Mishra","year":"2019","journal-title":"Gene."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"104270","DOI":"10.1016\/j.jri.2024.104270","article-title":"MMP2 and MMP9 are associated with the pathogenesis of recurrent pregnancy loss through protein expression rather than genetic polymorphism.","volume":"164","author":"S Goto","year":"2024","journal-title":"J. Reprod. Immunol."},{"key":"ref20","doi-asserted-by":"publisher","article-title":"Peripheral Blood Expression of MMPs and DNA Methylation-Related Genes in Women with Recurrent Spontaneous Abortion: A Case-Control Study.","author":"M Imani","DOI":"10.6084\/m9.figshare.29262128"}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/14-763\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/14-763\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/14-763\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T09:49:35Z","timestamp":1779875375000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/14-763\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,6]]},"references-count":22,"URL":"https:\/\/doi.org\/10.12688\/f1000research.166306.2","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/f1000research.166306.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.189089.r420793","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.189089.r420793","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,6]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/14-763\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.183273.r403503, Noor Nihad Baqer, Research and Technology Center of Environment, Baghdad, 02 Sep 2025, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/14-763\/v1#referee-response-403503","order":0,"name":"referee-response-403503","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Farzaneh Fesahat<\/b>; \n<i>Posted: 14 Sep 2025<\/i>; We sincerely thank the reviewer for their thoughtful and constructive feedback. We fully agree with the importance of incorporating regional studies, particularly from neighboring countries such as Iraq, given the shared genetic and ethnic backgrounds that may influence gene polymorphism patterns. In line with this valuable suggestion, we have cited the recommended article\u2014&quot;Association between Methylenetetrahydrofolate Reductase (MTHFR) and 5-Methyltetrahydrofolate-Homocysteine Methyltransferase Reductase (MTRR) Polymorphisms in Iraqi Patients with COVID-19&quot;\u2014in the revised manuscript.","URL":"https:\/\/f1000research.com\/articles\/14-763\/v2#referee-comment-14581","order":1,"name":"referee-comment-14581","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.189089.r420793, Nafisa Huseni Balasinor, ICMR-National Institute for Research in Reproductive & Child Health, Mumbai, Maharashtra, 14 Oct 2025, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/14-763\/v2#referee-response-420793","order":2,"name":"referee-response-420793","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}