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In this study, we investigated the impact of the NAD\n                    <jats:sup>+<\/jats:sup>\n                    de novo synthesis pathway on spermatogenesis by generating\n                    <jats:italic>Qprt<\/jats:italic>\n                    \u2010deficient mice using CRISPR\u2010Cas9 to target quinolinate phosphoribosyl transferase (\n                    <jats:italic>Qprt<\/jats:italic>\n                    ), a key enzyme predominantly expressed in spermatocytes. Our results revealed that the deletion of\n                    <jats:italic>Qprt<\/jats:italic>\n                    did not affect NAD\n                    <jats:sup>+<\/jats:sup>\n                    levels or spermatogenesis in the testes of 3\u2010month\u2010old mice. However, from 6\u2009months of age onward,\n                    <jats:italic>Qprt<\/jats:italic>\n                    \u2010deficient mice exhibited significantly reduced NAD\n                    <jats:sup>+<\/jats:sup>\n                    levels in the testes compared to wild\u2010type (WT) controls, along with a notable decrease in germ cell numbers and increased apoptosis. Additionally, these mice demonstrated mitochondrial dysfunction in spermatocytes, impaired progression through prophase I of meiosis, defective double\u2010strand break (DSB) repair, and abnormal meiotic sex chromosome inactivation. Importantly, supplementation with the NAD\n                    <jats:sup>+<\/jats:sup>\n                    precursor nicotinamide riboside (NR) in\n                    <jats:italic>Qprt<\/jats:italic>\n                    \u2010deficient mice restored NAD\n                    <jats:sup>+<\/jats:sup>\n                    levels and rescued the spermatogenic defects. These findings underscore the critical role of NAD\n                    <jats:sup>+<\/jats:sup>\n                    de novo synthesis in maintaining NAD\n                    <jats:sup>+<\/jats:sup>\n                    homeostasis and highlight its importance in meiotic recombination and meiotic sex chromosome inactivation in spermatogenesis.\n                  <\/jats:p>","DOI":"10.1111\/acel.70004","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T04:54:57Z","timestamp":1738644897000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Nicotinamide Riboside Supplementation Alleviates Testicular Aging Induced by Disruption of Qprt\u2010Dependent\n                    <scp>NAD<\/scp>\n                    <sup>+<\/sup>\n                    De Novo Synthesis in 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