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However, the physiological importance of proteasomal degradation in mammalian spermiogenesis remains largely unknown. Here, we report that the PSMA8\u2010containing spermato\u201020S proteasome (s20S) is required for spermiogenesis and male fertility in mice. In a mutant mouse model that the C\u2010terminal 30\u2010amino\u2010acid (C30) of PSMA8 is substituted by PSMA7\u2010C30, the resulting PSMA8\n                    <jats:sup>7C30<\/jats:sup>\n                    protein is unstable, which further disrupts the assembly of s20S and subcellular localization of 19S regulatory particle in testes.\n                    <jats:italic>\n                      Psma8\n                      <jats:sup>7C30<\/jats:sup>\n                    <\/jats:italic>\n                    males could produce round spermatids, but sperm formation is delayed and abnormal, exhibiting a phenotype of oligoasthenoteratozoospermia. s20S is required for the ubiquitination\u2010dependent proteasomal degradation of a group of proteins in elongating spermatids. These s20S\u2010mediated degradation events are essential for liquid\u2010liquid phase separation of FXR1 and thereby translational\u2010activation of its substrates. Taken together, these findings provide an in vivo evidence of protein homeostasis control in spermiogenesis in mammals.\n                  <\/jats:p>","DOI":"10.1002\/advs.202520292","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T12:03:51Z","timestamp":1776081831000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PSMA8\u2010Containing 20S Proteasome Regulates Spermiogenesis and Male Fertility"],"prefix":"10.1002","volume":"13","author":[{"given":"Huiwen","family":"Cao","sequence":"first","affiliation":[{"name":"MOE Key Laboratory of Biosystems Homeostasis &amp; Protection College of Life Sciences Zhejiang University  Hangzhou China"},{"name":"Zhejiang University\u2010University of Edinburgh Institute (ZJU\u2010UoE Institute) Zhejiang University School of Medicine Zhejiang University  Haining 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