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Their biogenesis and function are poorly understood as they are characterized by sequence homology with linear DNA, for which few detection methods are available. Recent advances in high-throughput sequencing technologies have revealed that eccDNAs play crucial roles in tumor formation, evolution, and drug resistance as well as aging, genomic diversity, and other biological processes, bringing it back to the research hotspot. Several mechanisms of eccDNA formation have been proposed, including the breakage-fusion-bridge (BFB) and translocation\u2013deletion\u2013amplification models. Gynecologic tumors and disorders of embryonic and fetal development are major threats to human reproductive health. The roles of eccDNAs in these pathological processes have been partially elucidated since the first discovery of eccDNA in pig sperm and the double minutes in ovarian cancer ascites. The present review summarized the research history, biogenesis, and currently available detection and analytical methods for eccDNAs and clarified their functions in gynecologic tumors and reproduction. We also proposed the application of eccDNAs as drug targets and liquid biopsy markers for prenatal diagnosis and the early detection, prognosis, and treatment of gynecologic tumors. This review lays theoretical foundations for future investigations into the complex regulatory networks of eccDNAs in vital physiological and pathological processes.<\/jats:p>","DOI":"10.1093\/procel\/pwad032","type":"journal-article","created":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T14:59:36Z","timestamp":1685113176000},"page":"6-20","source":"Crossref","is-referenced-by-count":20,"title":["Innovative insights into extrachromosomal circular DNAs in gynecologic tumors and reproduction"],"prefix":"10.1093","volume":"15","author":[{"given":"Ning","family":"Wu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital , Beijing 100191 , China"},{"name":"National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital , Beijing 100191 , China"},{"name":"Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education , Beijing 100191 , China"},{"name":"Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology , Beijing 100191 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Wei","sequence":"additional","affiliation":[{"name":"Institute of Medical Innovation and Research, Peking University Third Hospital , Beijing 100191 , China"},{"name":"Cancer Center, Peking University Third Hospital , Beijing 100191 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhipeng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Medical Innovation and Research, Peking University Third Hospital , Beijing 100191 , China"},{"name":"Cancer Center, Peking University Third Hospital , Beijing 100191 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital , Beijing 100191 , China"},{"name":"National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital , Beijing 100191 , China"},{"name":"Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education , Beijing 100191 , China"},{"name":"Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology , Beijing 100191 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell 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China"},{"name":"Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education , Beijing 100191 , China"},{"name":"Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology , Beijing 100191 , China"},{"name":"Beijing Advanced Innovation Center for Genomics , Beijing 100191 , China"},{"name":"Peking-Tsinghua Center for Life Sciences, Peking University , Beijing 100191 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6864-0771","authenticated-orcid":false,"given":"Xiaolu","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital , Beijing 100191 , China"},{"name":"National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital , Beijing 100191 , China"},{"name":"Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education , Beijing 100191 , China"},{"name":"Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology , Beijing 100191 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,5,26]]},"reference":[{"key":"2024010310451370000_CIT0001","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nm.3984","article-title":"Pan-cancer analysis of the extent and consequences of intratumor heterogeneity","volume":"22","author":"Andor","year":"2016","journal-title":"Nat Med"},{"key":"2024010310451370000_CIT0002","first-page":"450","article-title":"Chromosome changes in early gynecologic malignancies","volume":"27","author":"Atkin","year":"1983","journal-title":"Acta 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