{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T04:27:46Z","timestamp":1747369666473,"version":"3.40.5"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Infertility is a significant challenge in modern society, and observed studies have reported the association between telomere length and infertility. Whether this relationship is causal remains controversial.We employed two-sample mendelian randomization (MR) to investigate the causal relationship between leukocyte telomere length (LTL) and major causes of infertility, including male and female infertility, sperm abnormalities, and endometriosis. MR analyses were mainly performed using the inverse variance weighted (IVW) method and complemented with other MR methods.Our findings demonstrate a causal association between LTL and endometriosis (OR1.304, 95% CI (1.122,1.517), p = 0.001), suggesting its potential as a biomarker for this condition. However, we did not observe a significant causal relationship between LTL and other infertility causes.Our study presents compelling evidence on the relationship between LTL and endometriosis. Meanwhile, our study demonstrates that there is no causal relationship between LTL and infertility. This research contributes to the field by shedding light on the importance of LTL in the early diagnosis and intervention of endometriosis.<\/jats:p>","DOI":"10.1371\/journal.pone.0298997","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T17:43:55Z","timestamp":1711043035000},"page":"e0298997","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unraveling the causal association between leukocyte telomere length and infertility: A two-sample Mendelian randomization study"],"prefix":"10.1371","volume":"19","author":[{"given":"Gaole","family":"An","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingnan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2059-630X","authenticated-orcid":true,"given":"Chenghui","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,3,21]]},"reference":[{"issue":"6265","key":"pone.0298997.ref001","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1126\/science.aab3389","article-title":"Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection","volume":"350","author":"EH Blackburn","year":"2015","journal-title":"Science"},{"issue":"1","key":"pone.0298997.ref002","doi-asserted-by":"crossref","DOI":"10.3390\/cells8010073","article-title":"Telomere Biology and Human Phenotype.","volume":"8","author":"KJ Turner","year":"2019","journal-title":"Cells"},{"issue":"3","key":"pone.0298997.ref003","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1001\/jamainternmed.2021.7804","article-title":"Association of Telomere Length With Risk of Disease and Mortality.","volume":"182","author":"CV Schneider","year":"2022","journal-title":"JAMA Intern Med"},{"issue":"3","key":"pone.0298997.ref004","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.fertnstert.2017.06.005","article-title":"The International Glossary on Infertility and Fertility Care, 2017","volume":"108","author":"F Zegers-Hochschild","year":"2017","journal-title":"Fertil Steril"},{"issue":"2","key":"pone.0298997.ref005","first-page":"375","article-title":"The association of female and male infertility with telomere length (Review).","volume":"44","author":"E Vasilopoulos","year":"2019","journal-title":"Int J Mol Med"},{"issue":"10","key":"pone.0298997.ref006","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1007\/s43032-020-00214-6","article-title":"Peripheral Blood Leukocyte Telomere Length and Endometriosis.","volume":"27","author":"N Sasamoto","year":"2020","journal-title":"Reprod Sci"},{"issue":"5","key":"pone.0298997.ref007","doi-asserted-by":"crossref","first-page":"e13546","DOI":"10.1111\/and.13546","article-title":"Relationship between sperm telomere length and sperm quality in infertile men","volume":"52","author":"Z Darmishonnejad","year":"2020","journal-title":"Andrologia"},{"issue":"8","key":"pone.0298997.ref008","first-page":"1133","article-title":"Mendelian randomization: using genes as instruments for making causal inferences in epidemiology.","volume":"27","author":"DA Lawlor","year":"2008"},{"issue":"3","key":"pone.0298997.ref009","first-page":"713","article-title":"An examination of multivariable Mendelian randomization in the single-sample and two-sample summary data settings.","volume":"48","author":"E Sanderson","year":"2019"},{"issue":"10","key":"pone.0298997.ref010","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1038\/s41588-021-00944-6","article-title":"Polygenic basis and biomedical consequences of telomere length variation","volume":"53","author":"V Codd","year":"2021","journal-title":"Nat Genet"},{"issue":"2","key":"pone.0298997.ref011","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/s41588-018-0307-5","article-title":"Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use","volume":"51","author":"M Liu","year":"2019","journal-title":"Nat Genet"},{"key":"pone.0298997.ref012","doi-asserted-by":"crossref","first-page":"k601","DOI":"10.1136\/bmj.k601","article-title":"Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians","volume":"362","author":"NM Davies","year":"2018","journal-title":"BMJ"},{"issue":"7","key":"pone.0298997.ref013","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/gepi.21758","article-title":"Mendelian randomization analysis with multiple genetic variants using summarized data","volume":"37","author":"S Burgess","year":"2013","journal-title":"Genet Epidemiol"},{"issue":"5","key":"pone.0298997.ref014","first-page":"693","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases.","volume":"50","author":"M Verbanck","year":"2018"},{"key":"pone.0298997.ref015","first-page":"7","article-title":"The MR-Base platform supports systematic causal inference across the human phenome.","author":"G Hemani","year":"2018","journal-title":"Elife."},{"issue":"5","key":"pone.0298997.ref016","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s10654-017-0255-x","article-title":"Interpreting findings from Mendelian randomization using the MR-Egger method","volume":"32","author":"S Burgess","year":"2017","journal-title":"Eur J Epidemiol"},{"issue":"2","key":"pone.0298997.ref017","first-page":"305","volume":"100","author":"MS Rocca","year":"2019","journal-title":"Telomere length: lights and shadows on their role in human reproduction"},{"key":"pone.0298997.ref018","doi-asserted-by":"crossref","first-page":"101507","DOI":"10.1016\/j.arr.2021.101507","article-title":"Stress and telomere shortening: Insights from cellular mechanisms.","volume":"73","author":"J Lin","year":"2022","journal-title":"Ageing Res Rev"},{"issue":"1","key":"pone.0298997.ref019","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.aju.2017.11.001","article-title":"Role of reactive oxygen species in male infertility: An updated review of literature","volume":"16","author":"H Wagner","year":"2018","journal-title":"Arab J Urol"},{"issue":"4","key":"pone.0298997.ref020","first-page":"648","article-title":"Shorter leukocyte telomere length is associated with risk of nonobstructive azoospermia.","volume":"110","author":"Q Yang","year":"2018"},{"issue":"8","key":"pone.0298997.ref021","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22083959","article-title":"Telomere Length and Male Fertility.","volume":"22","author":"M Gentiluomo","year":"2021","journal-title":"Int J Mol Sci."},{"issue":"4","key":"pone.0298997.ref022","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1111\/cen.13283","article-title":"Telomeric repeat-containing RNA (TERRA) related to polycystic ovary syndrome (PCOS).","volume":"86","author":"C Wang","year":"2017","journal-title":"Clin Endocrinol (Oxf)."},{"issue":"5","key":"pone.0298997.ref023","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1177\/1933719115611753","article-title":"A Nonrandomized Trial of Progressive Resistance Training Intervention in Women With Polycystic Ovary Syndrome and Its Implications in Telomere Content.","volume":"23","author":"CL Miranda-Furtado","year":"2016","journal-title":"Reprod Sci."},{"issue":"1","key":"pone.0298997.ref024","first-page":"1","article-title":"Telomere length in granulosa cells and leukocytes: a potential marker of female fertility?","volume":"13","author":"A-J Fattet","year":"2020","journal-title":"A systematic review of the literature."},{"issue":"19","key":"pone.0298997.ref025","first-page":"1925","volume":"318","author":"CA Emdin","year":"2017","journal-title":"Mendelian randomization."},{"issue":"1","key":"pone.0298997.ref026","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41572-018-0008-5","article-title":"Endometriosis.","volume":"4","author":"KT Zondervan","year":"2018","journal-title":"Nat Rev Dis Primers"},{"issue":"1","key":"pone.0298997.ref027","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s13669-017-0187-1","article-title":"Endometriosis: Epidemiology, Diagnosis and Clinical Management.","volume":"6","author":"P Parasar","year":"2017","journal-title":"Curr Obstet Gynecol Rep."},{"journal-title":"Endometriosis overview","year":"2023","author":"WHO","key":"pone.0298997.ref028"},{"issue":"12","key":"pone.0298997.ref029","first-page":"588","article-title":"Endometriosis is associated with a significant increase in hTERC and altered telomere\/telomerase associated genes in the eutopic endometrium, an ex-vivo and in silico study.","volume":"8","author":"R Alnafakh","year":"2020"},{"issue":"2","key":"pone.0298997.ref030","first-page":"166","article-title":"Implications of telomeres and telomerase in endometrial pathology","volume":"23","author":"DK Hapangama","year":"2017","journal-title":"Hum Reprod Update"},{"issue":"4","key":"pone.0298997.ref031","first-page":"476","article-title":"Reduced telomere length in rheumatoid arthritis is independent of disease activity and duration.","volume":"66","author":"SE Steer","year":"2007"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0298997","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T17:44:17Z","timestamp":1711043057000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0298997"}},"subtitle":[],"editor":[{"given":"Arthur J.","family":"Lustig","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,3,21]]},"references-count":31,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0298997","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2024,3,21]]}}}