{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:15:28Z","timestamp":1770336928024,"version":"3.49.0"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,4,22]],"date-time":"2023-04-22T00:00:00Z","timestamp":1682121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The family of WWC proteins is known to regulate cell proliferation and organ growth control via the Hippo signaling pathway. As WWC proteins share a similar domain structure and a common set of interacting proteins, they are supposed to fulfill compensatory functions in cells and tissues. While all three WWC family members WWC1, WWC2, and WWC3 are found co\u2010expressed in most human organs including lung, brain, kidney, and liver, in the testis only WWC2 displays a relatively high expression. In this study, we investigated the testicular WWC2 expression in spermatogenesis and male fertility. We show that the\n                    <jats:italic>Wwc2<\/jats:italic>\n                    mRNA expression level in mouse testes is increased during development in parallel with germ cell proliferation and differentiation. The cellular expression of each individual\n                    <jats:italic>WWC<\/jats:italic>\n                    family member was evaluated in published single\u2010cell mRNA datasets of murine and human testes demonstrating a high\n                    <jats:italic>WWC2<\/jats:italic>\n                    expression predominantly in early spermatocytes. In line with this, immunohistochemistry revealed cytosolic WWC2 protein expression in primary spermatocytes from human testes displaying full spermatogenesis. In accordance with these findings, markedly lower\n                    <jats:italic>WWC2<\/jats:italic>\n                    expression levels were detected in testicular tissues from mice and men lacking germ cells. Finally, analysis of whole\u2010exome sequencing data of male patients affected by infertility and unexplained severe spermatogenic failure revealed several heterozygous, rare\n                    <jats:italic>WWC2<\/jats:italic>\n                    gene variants with a proposed damaging function and putative impact on WWC2 protein structure. Taken together, our findings provide novel insights into the testicular expression of\n                    <jats:italic>WWC2<\/jats:italic>\n                    and show its cell\u2010specific expression in spermatocytes. As rare\n                    <jats:italic>WWC2<\/jats:italic>\n                    variants were identified in the background of disturbed spermatogenesis,\n                    <jats:italic>WWC2<\/jats:italic>\n                    may be a novel candidate gene for male infertility.\n                  <\/jats:p>","DOI":"10.1096\/fj.202200960r","type":"journal-article","created":{"date-parts":[[2023,4,22]],"date-time":"2023-04-22T06:04:28Z","timestamp":1682143468000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>WWC2<\/scp>\n                    expression in the testis: Implications for spermatogenesis and male fertility"],"prefix":"10.1096","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1689-5462","authenticated-orcid":false,"given":"Verena","family":"H\u00f6ffken","sequence":"first","affiliation":[{"name":"Institute of Molecular Nephrology, Internal Medicine D University Hospital 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