{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T09:55:55Z","timestamp":1790589355597,"version":"4.1.0"},"reference-count":138,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"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:p>Idiopathic male infertility (IMI) usually refers to abnormal semen parameters after known causes have been excluded. However, its clinical stratification and intervention evidence remain difficult to reconcile. Based on low biomass in semen, this review proposes an SD\u2013IO\u2013SDF axis linking seminal dysbiosis (SD), inflammatory\/oxidative endophenotype (IO), and sperm DNA fragmentation (SDF) in subsets of IMI. It integrates three mechanisms of evidence strength: (i) inflammation\u2013oxidative injury pathway (leukocyte-dependent); (ii) leukocyte-independent redox imbalance; and (iii) a metabolic\u2013epigenetic route (SAM cycle, butyrate) as a testable hypothesis. Existing evidence suggests that the association between SD and SDF concentrates in specific IO activation states and IMI subtypes. IO stratification may reduce effect dilution across mixed populations and make the hypothesis more directly testable. For research implementation, we propose IO indicators grouped by measurement type (inflammatory: leukocytospermia and\/or PMN-elastase; oxidative: sORP), with validation against SDF platforms as a subsequent step. This approach provides a falsifiable structure for IMI and provides a template for future trial designs based on SD\u00d7IO stratification.<\/jats:p>","DOI":"10.3389\/fendo.2026.1943471","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T09:07:09Z","timestamp":1790586429000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Seminal dysbiosis in idiopathic male infertility: toward a seminal dysbiosis\u2013inflammatory\/oxidative endophenotype\u2013SDF axis"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuan","family":"Gao","sequence":"first","affiliation":[{"name":"Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqia","family":"Lv","sequence":"additional","affiliation":[{"name":"Henan Province Hospital of Traditional Chinese Medicine (The Second Affiliated Hospital of Henan University of Chinese Medicine)","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixue","family":"Sun","sequence":"additional","affiliation":[{"name":"Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Henan Province Hospital of Traditional Chinese Medicine (The Second Affiliated Hospital of Henan University of Chinese Medicine)","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32667-2","article-title":"Male infertility","volume":"397","author":"Agarwal","year":"2021","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2014.10.021","article-title":"Limitations of semen analysis as a test of male fertility and anticipated needs from newer tests","volume":"102","author":"Wang","year":"2014","journal-title":"Fertil Steril"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.5534\/wjmh.220069","article-title":"Is there a relevant clinical impact in differentiating idiopathic versus unexplained male infertility","volume":"41","author":"Corsini","year":"2023","journal-title":"World J Mens Health"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1293368","article-title":"Micrornas in spermatogenesis dysfunction and male infertility: Clinical phenotypes, mechanisms and potential diagnostic biomarkers","volume":"15","author":"Shi","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1097\/ju.0000000000004180","article-title":"Updates to male infertility: Aua\/asrm guideline (2024)","volume":"212","author":"Brannigan","year":"2024","journal-title":"J Urol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/antiox15030293","article-title":"Oxidative stress, sperm DNA fragmentation, or both? 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