{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T12:13:44Z","timestamp":1774440824349,"version":"3.50.1"},"reference-count":58,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,9,20]],"date-time":"2017-09-20T00:00:00Z","timestamp":1505865600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Italian Ministry of Education"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:sec><jats:label\/><jats:p>We previously demonstrated that the nuclear form of Glutathione peroxidase 4 (nGPx4) has a peculiar distribution in sperm head, being localized to nuclear matrix and acrosome and that sperm lacking nGPx4 are more prone to decondensation in vitro. In this study we have hypothesized that sperm retained acetylated histones and nGPx4 are implicated in paternal chromatin decondensation and male pronucleus formation at fertilization. Indeed, significant higher amounts of acetylated histone H4 and acetylated histone H3 were observed by both immunofluorescence and western blotting in nGPx4\u2010KO sperm vs WT ones. In vitro fertilization of zona pellucida\u2010deprived oocytes by WT sperm in the presence of trichostatin (TSA) also demonstrated that paternal histone acetylation was inversely related to the timing of sperm nucleus decondensation at fertilization. In contrast, TSA had no effect on nGPx4\u2010KO sperm, indicating they had a maximal level of histone acetylation. Moreover the paternally imprinted gene Igf2\/H19 was hypomethylated in KO sperm compared to WT ones. The lack of nGPx4 negatively affected male fertility, causing a marked decrease in total pups and pregnancies with delivery, a significant reduction in pronuclei (PN) embryos in in vitro fertilization assays and an approximately 2\u2009h delay in egg fertilization in vivo. Because the zona pellucida binding and fusion to oolemma of nGPx4\u2010KO and WT sperm were similar, the subfertility of nGPx4 sperm reflected a decreased sperm progression through egg cumulus\/zona pellucida, pinpointing a defective acrosome in line with acrosomal nGPx4 localization. We conclude that paternal acetylated histones and acrosomal nGPx4 are directly involved in fertilization.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.26146","type":"journal-article","created":{"date-parts":[[2017,8,12]],"date-time":"2017-08-12T09:56:39Z","timestamp":1502531799000},"page":"3093-3104","source":"Crossref","is-referenced-by-count":10,"title":["Involvement of sperm acetylated histones and the nuclear isoform of Glutathione peroxidase 4 in fertilization"],"prefix":"10.1002","volume":"233","author":[{"given":"Simona","family":"Pipolo","sequence":"first","affiliation":[{"name":"Department of Anatomical Histological Forensic and Orthopedic Sciences \u2212 Section of Histology and Medical Embryology Sapienza University of Rome Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rossella","family":"Puglisi","sequence":"additional","affiliation":[{"name":"Department of Anatomical Histological Forensic and Orthopedic Sciences \u2212 Section of Histology and Medical Embryology Sapienza University of Rome Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Mularoni","sequence":"additional","affiliation":[{"name":"Department of Anatomical Histological Forensic and Orthopedic Sciences \u2212 Section of Histology and Medical Embryology Sapienza University of Rome Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Anatomical Histological Forensic and Orthopedic Sciences \u2212 Section of Histology and Medical Embryology Sapienza University of Rome Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Fuso","sequence":"additional","affiliation":[{"name":"Department of Surgery \u201cP. 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