{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T05:07:11Z","timestamp":1787461631332,"version":"build-2736575974"},"reference-count":75,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T00:00:00Z","timestamp":1717718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01ES033345"],"award-info":[{"award-number":["R01ES033345"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL134779"],"award-info":[{"award-number":["R01HL134779"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Agricultural Higher Education Project"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Perfluoroalkyl and poly-fluoroalkyl substances (PFAS) are pervasive environmental pollutants and potential threats to reproductive health. Epidemiological studies have established an association between PFAS and male infertility, but the underlying mechanisms are unclear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Investigate the effect of perfluorooctane sulfonic acid (PFOS), the most prevalent and representative PFAS, on bull sperm protein phosphorylation and function.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We exposed bull sperm to PFOS at 10 (average population exposure) and 100\u00a0\u03bcM (high-exposure scenario), and analyzed global proteomic and phosphoproteomic analysis by TMT labeling and Nano LC-MS\/MS. We also measured sperm fertility functions by flow cytometry.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>PFOS at 10-\u03bcM altered sperm proteins linked to spermatogenesis and chromatin condensation, while at 100\u00a0\u03bcM, PFOS affected proteins associated with motility and fertility. We detected 299 phosphopeptides from 116 proteins, with 45 exhibiting differential expression between control and PFOS groups. PFOS dysregulated phosphorylation of key proteins (ACRBP, PRKAR2A, RAB2B, SPAG8, TUBB4B, ZPBP, and C2CD6) involved in sperm capacitation, acrosome reaction, sperm\u2013egg interaction, and fertilization. PFOS also affected phosphorylation of other proteins (AQP7, HSBP9, IL4I1, PRKAR1A, and CCT8L2) related to sperm stress resistance and cryotolerance. Notably, four proteins (PRM1, ACRBP, TSSK1B, and CFAP45) exhibited differential regulation at both proteomic and phosphoproteomic levels. Flow cytometric analysis confirmed that PFOS increased protein phosphorylation in sperm and also decreased sperm motility, viability, calcium, and mitochondrial membrane potential and increased mitochondrial ROS in a dose-dependent manner.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study demonstrates that PFOS exposure negatively affects phosphorylation of proteins vital for bull sperm function and fertilization.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/biolre\/ioae089","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T12:35:37Z","timestamp":1717763737000},"page":"723-739","source":"Crossref","is-referenced-by-count":11,"title":["Male infertility and perfluoroalkyl and poly-fluoroalkyl substances: evidence for alterations in phosphorylation of proteins and fertility-related functional attributes in bull spermatozoa"],"prefix":"10.1093","volume":"111","author":[{"given":"Arumugam","family":"Kumaresan","sequence":"first","affiliation":[{"name":"Department of Comparative Biosciences , School of Veterinary Medicine, , Madison, WI 53706 , USA"},{"name":"University of Wisconsin-Madison , School of Veterinary Medicine, , Madison, WI 53706 , USA"},{"name":"Theriogenology Laboratory, Southern Regional Station of ICAR National Dairy Research Institute , Bengaluru, Karnataka 560030 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Yadav","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences , School of Veterinary Medicine, , Madison, WI 53706 , USA"},{"name":"University of Wisconsin-Madison , School of Veterinary Medicine, , Madison, WI 53706 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish Kumar","family":"Sinha","sequence":"additional","affiliation":[{"name":"Theriogenology Laboratory, Southern Regional Station of ICAR National Dairy Research Institute , Bengaluru, Karnataka 560030 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep","family":"Nag","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, University of Missouri , Columbia, WI 65211 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebenezer Samuel King","family":"John Peter","sequence":"additional","affiliation":[{"name":"Theriogenology Laboratory, Southern Regional Station of ICAR National Dairy Research Institute , Bengaluru, Karnataka 560030 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay S","family":"Mishra","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences , School of Veterinary Medicine, , Madison, WI 53706 , USA"},{"name":"University of Wisconsin-Madison , School of Veterinary Medicine, , Madison, WI 53706 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sathish","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences , School of Veterinary Medicine, , Madison, WI 53706 , USA"},{"name":"University of Wisconsin-Madison , School of Veterinary Medicine, , Madison, WI 53706 , USA"},{"name":"Department of Obstetrics and Gynecology , School of Medicine and Public Health, , WI 53706 , USA"},{"name":"University of Wisconsin-Madison , School of Medicine and Public Health, , WI 53706 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,6,7]]},"reference":[{"key":"2024091602160311800_ref1","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1136\/bmj.305.6854.609","article-title":"Evidence for decreasing quality of semen during past 50 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