{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T07:21:46Z","timestamp":1787556106160,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Spermiogenesis is the final phase of sperm development during which haploid round spermatids transform into specialized spermatozoa and occurs across distinct stages of sperm production in the seminiferous epithelium. Abnormalities in this process lead to malformations and an inability of sperm to fertilize eggs. Previous studies demonstrated that the alpha\u2010arrestin family molecule alpha\u2010arrestin domain\u2010containing 5 (\n                      <jats:italic>Arrdc5)<\/jats:italic>\n                      is required for normal spermiogenesis in mice; however, the mechanism of action is undefined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To further describe the role\n                      <jats:italic>ARRDC5<\/jats:italic>\n                      plays in spermiogenesis, a description of the expression profile is needed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Here, single cell RNA\u2010sequencing and single cell ATAC\u2010sequencing datasets generated from testicular tissue of mice and men were computationally integrated to define cell\u2010type expression profiles and chromatin accessibility of\n                      <jats:italic>ARRDC5<\/jats:italic>\n                      and other alpha\u2010arrestin family member loci. To validate computational data, in situ hybridization of both mouse and human testicular tissue was probed for\n                      <jats:italic>ARRDC5<\/jats:italic>\n                      transcript abundance. Subsequently, immunohistochemistry was used on an\n                      <jats:italic>Arrdc5\u2010eGfp<\/jats:italic>\n                      mouse model to measure ARRDC5 protein expression. Lastly, the motif\u2010based sequence analysis tool MEME was used to predict RNA\u2010binding protein (RBP) motifs in the mouse and human\n                      <jats:italic>ARRDC5<\/jats:italic>\n                      transcripts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the six alpha\u2010arrestin family members, the\n                      <jats:italic>ARRDC5<\/jats:italic>\n                      locus was found to be uniquely in a heterochromatin state in testicular somatic cells but remodeled into an open euchromatin state specifically in spermatids. Concomitantly,\n                      <jats:italic>Arrdc5<\/jats:italic>\n                      transcripts are uniquely detected in spermatids of both mice and humans. Additionally, in mice, transcript abundance peaks in stages VI\u2013VIII of the seminiferous epithelium, and subsequent ARRDC5 protein abundance was found to be present in all steps of spermatid development with peaks in stages IX\u2013XII of the seminiferous cycle. Outcomes of RNA motif analysis identified several conserved testis\u2010specific RBPs with predicted binding to both mouse and human\n                      <jats:italic>ARRDC5<\/jats:italic>\n                      transcripts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Collectively, these findings provide evidence that spermatid\u2010specific transcription of the\n                      <jats:italic>Arrdc5<\/jats:italic>\n                      locus is driven by remodeling of the chromatin landscape. Furthermore, the temporal peak of ARRDC5 expression in specific stages during spermiogenesis coincides with critical events in spermatid development, including the histone\u2010to\u2010protamine exchange, acrosome formation, and cytoplasmic droplet biogenesis, implicating ARRDC5 in orchestrating these processes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70356","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T06:55:46Z","timestamp":1787554546000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatiotemporal Expression of ARRDC5 in Mammalian Spermatogenesis"],"prefix":"10.1111","author":[{"given":"LeeLa D.","family":"Robinson","sequence":"first","affiliation":[{"name":"Center For Reproductive Biology School of Molecular Biosciences College of Veterinary Medicine Washington State University  Pullman Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6692-4351","authenticated-orcid":false,"given":"Jon M.","family":"Oatley","sequence":"additional","affiliation":[{"name":"Center For Reproductive Biology School of Molecular Biosciences College of Veterinary Medicine Washington State University  Pullman Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,23]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Histological and Histopathological Evaluation of the Testis","author":"Russell L. 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