{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:13:46Z","timestamp":1787026426589,"version":"build-2736575974"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"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>Backgrounds<\/jats:title>\n                    <jats:p>Varicocele is a leading cause of male infertility, primarily manifesting as asthenozoospermia. The underlying molecular mechanisms remain unclear, and the potential role of protein lactylation in this condition is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a comprehensive lactylome analysis using data-independent acquisition (DIA) mass spectrometry on paired sperm samples collected from patients with varicocele-associated asthenozoospermia before and after treatment. Differential lactylation analysis and bioinformatic enrichment analyses were conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Disrupted lactate metabolism was observed in asthenozoospermic sperm, with decreased intracellular L-lactate and elevated seminal plasma L-lactate. This was concomitant with a global reduction in protein lactylation, particularly in the sperm midpiece and tail. Lactylome profiling identified 2,699 lactylation sites on 1,216 proteins. Comparison of pre- and post-treatment samples revealed 133 differentially lactylated proteins, which were significantly enriched in pathways critical for sperm motility, including glycolysis\/gluconeogenesis, microtubule-based movement, and flagellar assembly. Notably, lactylation abundance of key proteins (TEKT3, AKAP4, TUBA1A, AKAP3, TUBB4B) were significantly downregulated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study presents an initial characterization of the protein lactylation landscape in human sperm, revealing\u200b its alteration in the context of varicocele-associated asthenozoospermia. The findings suggest that dysregulation of the lactate-lactylation axis correlates with impaired sperm motility, potentially through concurrent alterations in energy metabolism and flagellar structure. This correlation underscores specific lactylation events that warrant future mechanistic investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1791920","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T04:35:08Z","timestamp":1782189308000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Alterations in the protein lactylation landscape of sperm from patients with varicocele-associated asthenozoospermia"],"prefix":"10.3389","volume":"17","author":[{"given":"Heran","family":"Cao","sequence":"first","affiliation":[{"name":"NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Liu","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Male Reproduction and Genetics, Guangdong 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