{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:49:55Z","timestamp":1791352195191,"version":"4.3.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Diminished ovarian reserve (DOR) leads to subfertility, infertility, and premature menopause, significantly compromising women\u2019s reproductive health. Although clinical evidence supports the effectiveness of acupuncture in improving ovarian reserve, treatment responses vary considerably among DOR patients, and the factors associated with favorable outcomes remain unclear. Serum microRNAs may serve as potential biomarkers for distinguishing acupuncture responders, warranting further investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and methods<\/jats:title>\n                    <jats:p>This prospective nested case-control study will enroll women with DOR who undergo acupuncture treatment. Treatment response will be evaluated based on changes in anti-M\u00fcllerian hormone (AMH) levels, antral follicle count (AFC), serum follicle stimulating hormone (FSH) levels and clinical pregnancy. According to their response, participants demonstrating greater improvement will be assigned to the experimental group (responders), while non-responders will be matched in a 1:1 ratio to form the control group. Serum microRNA profiles from both groups will be analyzed using high-throughput sequencing to identify differentially expressed microRNAs. Candidate microRNAs will subsequently be validated via real-time quantitative PCR (RT-qPCR), and receiver operating characteristic (ROC) curve analysis will be performed to evaluate their predictive value for acupuncture treatment response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This is the first clinical study to characterize the serum miRNA expression profiles of DOR patients who benefit from acupuncture. The findings are expected to provide evidence supporting the precise identification of acupuncture-responsive individuals within this patient population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study protocol registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/itmctr.ccebtcm.org.cn\/mgt\/project\/view\/-4614215526207679163<\/jats:ext-link>\n                      , identifier ITMCTR2025000004.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1972018","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:51:09Z","timestamp":1791348669000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum miRNA expression profile in responders to acupuncture treatment for diminished ovarian reserve: a study protocol for a nested case-control study"],"prefix":"10.3389","volume":"17","author":[{"given":"Dongxue","family":"An","sequence":"first","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiashan","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Hang","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyu","family":"Qi","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxi","family":"Meng","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenchen","family":"Su","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binbin","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Genetics, National Research Institute for Family Planning","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yigong","family":"Fang","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanfang","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deaa129","article-title":"Age-related natural fertility outcomes in women over 35 years: a systematic review and individual participant data meta-analysis","volume":"35","author":"Chua","year":"2020","journal-title":"Hum Reprod"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2020.09.134","article-title":"Testing and interpreting measures of ovarian reserve: a committee opinion","volume":"114","author":"Electronic address","year":"2020","journal-title":"Fertil Steril"},{"key":"B3","volume":"31","year":"2022","journal-title":"J Reprod Med."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1210\/er.2009-0006","article-title":"Ovarian aging: mechanisms and clinical consequences","volume":"30","author":"Broekmans","year":"2009","journal-title":"Endocr Rev"},{"key":"B5","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.tem.2007.01.004","article-title":"Female reproductive ageing: current knowledge and future trends","volume":"18","author":"Broekmans","year":"2007","journal-title":"Trends Endocrinol Metab"},{"key":"B6","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1016\/j.fertnstert.2023.01.029","article-title":"Diminished ovarian reserve is a risk factor for preeclampsia and placental malperfusion lesions","volume":"119","author":"Ganer Herman","year":"2023","journal-title":"Fertil Steril"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1080\/09513590.2020.1750001","article-title":"High incidence of diminished ovarian reserve in young unexplained recurrent pregnancy loss patients","volume":"36","author":"Wald","year":"2020","journal-title":"Gynecol Endocrinol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2024.11.007","article-title":"Evidence-based guideline: premature ovarian insufficiency","volume":"123","author":"Eshre","year":"2025","journal-title":"Fertil Steril"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.13703\/j.0255-2930.20210901-k0002","article-title":"Effect of electroacupuncture on endometrial receptivity and IVF-ET pregnancy outcomes in patients with diminished ovarian reserve","volume":"42","author":"Shen","year":"2022","journal-title":"Zhongguo Zhen Jiu"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.13703\/j.0255-2930.20230716-k0002","article-title":"Effect of Tiaojing Cuyun acupuncture therapy on pregnancy outcomes in women with diminished ovarian reserve undergoing IVF-ET: a cohort study","volume":"44","author":"Bai","year":"2024","journal-title":"Zhongguo Zhen Jiu"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2147\/ijwh.s580821","article-title":"Effect of acupuncture for diminished ovarian reserve: A randomized sham-controlled trial","volume":"18","author":"Wang","year":"2026","journal-title":"Int J Womens Health"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1136121","article-title":"Clinical efficacy of acupuncture for diminished ovarian reserve: a systematic review and meta-analysis of randomized controlled trials","volume":"14","author":"Lin","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2026.1840157","article-title":"Clinical evidence of acupuncture for infertile women with diminished ovarian reserve undergoing IVF\/ICSI: a systematic review and meta-analysis","volume":"17","author":"Xu","year":"2026","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.03.067","article-title":"Modulation of microRNA processing by p53","volume":"460","author":"Suzuki","year":"2009","journal-title":"Nature"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-012-1469-6","article-title":"Characterization and importance of microRNAs in mammalian gonadal functions","volume":"349","author":"Hossain","year":"2012","journal-title":"Cell Tissue Res"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1530\/rep-12-0025","article-title":"Identification of miRNAs associated with the follicular-luteal transition in the ruminant ovary","volume":"144","author":"McBride","year":"2012","journal-title":"Reproduction"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.108.069690","article-title":"Hormonal regulation of MicroRNA expression in periovulatory mouse mural granulosa cells","volume":"79","author":"Fiedler","year":"2008","journal-title":"Biol Reprod"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2014.12.106","article-title":"MicroRNA-22-3p is down-regulated in the plasma of Han Chinese patients with premature ovarian failure","volume":"103","author":"Dang","year":"2015","journal-title":"Fertil Steril"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1530\/rep-11-0371","article-title":"Differentially expressed plasma microRNAs in premature ovarian failure patients and the potential regulatory function of mir-23a in granulosa cell apoptosis","volume":"144","author":"Yang","year":"2012","journal-title":"Reproduction"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2023-081098","article-title":"Exploring the efficacy and safety of acupuncture versus sham acupuncture for diminished ovarian reserve: study protocol for a multicentre randomised controlled trial","volume":"14","author":"Xiao","year":"2024","journal-title":"BMJ Open"},{"key":"B21","volume-title":"WHO Standard Acupuncture Point Locations in the Western Pacific Region","year":"2008"},{"key":"B22","article-title":"Tiaojing Cuyun\" acupuncture therapy in diminished ovarian reserve: a randomized controlled trial","volume":"33","author":"Li","year":"2018","journal-title":"China J Traditional Chin Med Pharm"},{"key":"B23","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.wjam.2025.01.001","article-title":"Construction of a pregnancy prediction model in acupuncture treatment for diminished ovarian reserve based on machine learning","volume":"35","author":"Gou","year":"2025","journal-title":"World J Acupuncture-Moxibustion"},{"key":"B24","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s13048-015-0162-2","article-title":"MicroRNAs in ovarian function and disorders","volume":"8","author":"Li","year":"2015","journal-title":"J Ovarian Res"},{"key":"B25","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s12958-017-0256-3","article-title":"Role of microRNAs in premature ovarian insufficiency","volume":"15","author":"Guo","year":"2017","journal-title":"Reprod Biol Endocrinol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.968711","article-title":"Effects of acupuncture treatment on microRNAs expression in ovarian tissues from Tripterygium glycoside-induced diminished ovarian reserve rats","volume":"13","author":"Lu","year":"2022","journal-title":"Front Genet"},{"key":"B27","doi-asserted-by":"publisher","first-page":"13351","DOI":"10.1038\/s41598-021-92901-w","article-title":"Characterization of micro-RNA in women with different ovarian reserve","volume":"11","author":"Abu-Halima","year":"2021","journal-title":"Sci Rep"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.68028","article-title":"Mir-484 contributes to diminished ovarian reserve by regulating granulosa cell function via YAP1-mediated mitochondrial function and apoptosis","volume":"18","author":"Li","year":"2022","journal-title":"Int J Biol Sci"},{"key":"B29","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1095\/biolreprod.115.130690","article-title":"miR-23a and miR-27a promote human granulosa cell apoptosis by targeting SMAD5","volume":"93","author":"Nie","year":"2015","journal-title":"Biol Reprod"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1972018\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:51:22Z","timestamp":1791348682000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1972018\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":29,"alternative-id":["10.3389\/fendo.2026.1972018"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1972018","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"article-number":"1972018"}}