{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:58:06Z","timestamp":1788922686843,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Idiopathic male infertility (IMI), which accounts for nearly 50% of male infertility cases, remains a major clinical challenge due to the inability of standard semen analysis to reveal underlying molecular defects. Post-translational modifications such as lysine acetylation are increasingly recognized as key regulators of sperm function, affecting antioxidant defense, energy metabolism, and spermatogenesis. In this study, global acetyl-proteomic profiling of spermatozoa from idiopathic infertile patients (IIP) and fertile donors (FD) was performed using immunoprecipitation-based enrichment followed by high-resolution LC\u2013MS\/MS. Bioinformatics analyses, including STRING, Cytoscape, and Ingenuity Pathway Analysis (IPA), identified 718 differentially acetylated proteins (DAPs), with significant enrichment in pathways related to redox homeostasis, molecular transport, glycolysis, and mitochondrial metabolism. Hub proteins such as SOD1, PARK7, and PRKACA emerged as key regulators linking oxidative stress with defective motility and impaired sperm physiology. Western blot validation confirmed the downregulation of these hub proteins in IIP, supporting their role in redox imbalance and mitochondrial dysfunction. Our findings highlight dysregulated lysine acetylation as a defining molecular feature of IMI and suggest that targeting acetylation-associated pathways may provide novel diagnostic biomarkers and therapeutic strategies to improve sperm function and male reproductive outcomes.<\/jats:p>","DOI":"10.3390\/antiox14121410","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T13:56:34Z","timestamp":1764165394000},"page":"1410","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Spermatozoa Proteins Involved in ROS Generation and Antioxidant Defense Are Differentially Acetylated in Idiopathic Infertility"],"prefix":"10.3390","volume":"14","author":[{"given":"Lisa","family":"Goutami","sequence":"first","affiliation":[{"name":"Redox Biology & Proteomics Laboratory, Department of Zoology and Centre of Excellence for Environment and Public Health, Ravenshaw University, Cuttack 753003, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anwesha","family":"Pradhan","sequence":"additional","affiliation":[{"name":"Redox Biology & Proteomics Laboratory, Department of Zoology and Centre of Excellence for Environment and Public Health, Ravenshaw University, Cuttack 753003, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6928-218X","authenticated-orcid":false,"given":"Ajaya Kumar","family":"Moharana","sequence":"additional","affiliation":[{"name":"Redox Biology & Proteomics Laboratory, Department of Zoology and Centre of Excellence for Environment and Public Health, Ravenshaw University, Cuttack 753003, India"},{"name":"Department of Urology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8931-6818","authenticated-orcid":false,"given":"Soumya Ranjan","family":"Jena","sequence":"additional","affiliation":[{"name":"Redox Biology & Proteomics Laboratory, Department of Zoology and Centre of Excellence for Environment and Public Health, Ravenshaw University, Cuttack 753003, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9120-2278","authenticated-orcid":false,"given":"Manesh Kumar","family":"Panner Selvam","sequence":"additional","affiliation":[{"name":"Department of Urology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh C.","family":"Sikka","sequence":"additional","affiliation":[{"name":"Department of Urology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2969-0071","authenticated-orcid":false,"given":"Luna","family":"Samanta","sequence":"additional","affiliation":[{"name":"Redox Biology & Proteomics Laboratory, Department of Zoology and Centre of Excellence for Environment and Public Health, Ravenshaw University, Cuttack 753003, India"},{"name":"Department of Urology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100090","DOI":"10.1016\/j.cstres.2025.100090","article-title":"HSPA2 emerges as a key biomarker: Insights from global lysine acetylproteomic profiling in idiopathic male infertility","volume":"30","author":"Goutami","year":"2025","journal-title":"Cell Stress Chaperones"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1007\/s10815-017-0912-8","article-title":"Free radical and superoxide reactivity detection in semen quality assessment: Past, present, and future","volume":"34","author":"Gosalvez","year":"2017","journal-title":"J. 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