{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:18:43Z","timestamp":1787635123927,"version":"build-2736575974"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100031934","name":"First Affiliated Hospital of Xi'an Jiaotong University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100031934","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Impaired semen quality may involve concurrent abnormalities in sperm concentration, total sperm number, motility, morphology, and DNA integrity. The corresponding alterations in the seminal plasma metabolome remain incompletely characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To characterize seminal plasma metabolic alterations in men with multiple concurrent semen abnormalities and identify candidate signals associated with semen quality parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      Untargeted LC\u2013MS\/MS metabolomics was performed in a discovery cohort comprising 10 men with impaired semen quality and 9 normozoospermic controls. Candidate metabolites were screened using nominal p value and fold-change thresholds, followed by pathway and correlation analyses,\n                      <jats:italic>post hoc<\/jats:italic>\n                      ROC analysis, and qualitative comparisons with public datasets. External-calibration-derived estimates assigned to cytidine and 2-hydroxy-3-methylbutyric acid (2-HMBA) were subsequently evaluated by HPLC\u2013UV in an independent cohort of 18 men with impaired semen quality and 18 controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eighty-nine putatively annotated metabolites met the nominal screening criteria, but no individual metabolite remained significant after Benjamini\u2013Hochberg false discovery rate correction. Discovery-level pathway analyses highlighted nucleotide- and nucleoside-related processes as hypothesis-generating signals. Qualitative comparison with heterogeneous publicly available reproductive metabolomics datasets provided limited directional context but was not considered formal external validation. In the independent HPLC\u2013UV cohort, external-calibration-derived estimates assigned to 2-HMBA were nominally lower in the group with impaired semen quality (p = 0.030), but the difference did not remain significant after correction across the two candidate comparisons (q = 0.060). Cytidine showed no between-group difference (p = 0.812; q = 0.812).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion and conclusion<\/jats:title>\n                    <jats:p>The discovery-level nucleotide-related pathway signal and the independent observation concerning 2-HMBA represent distinct lines of evidence; the latter does not validate the former. Given the small sample sizes in both the discovery and independent HPLC\u2013UV evaluation cohorts, the absence of FDR-significant metabolites, heterogeneity across the public datasets, and limitations of the HPLC\u2013UV assay, these findings remain exploratory and hypothesis-generating. They do not constitute quantitative validation, establish a specific mechanism, or support clinical biomarker use. Larger multicenter cohorts and targeted quantitative metabolomic analyses using validated methods are needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1909718","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T04:23:29Z","timestamp":1787631809000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploratory seminal plasma metabolomics and independent HPLC\u2013UV evaluation in men with impaired semen quality"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiale","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Xi\u2019an Jiaotong University","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, The First Affiliated Hospital of Xi\u2019an Jiaotong University","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingxiao","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Xi\u2019an Jiaotong University","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Xi\u2019an Jiaotong University","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiqiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Xi\u2019an Jiaotong University","place":["Xi\u2019an, Shaanxi, 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