{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:32:21Z","timestamp":1786977141406,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171587"],"award-info":[{"award-number":["82171587"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Cryptorchidism, characterized by the failure of testicular descent, is a common congenital disorder adversely affecting male reproductive health. Intriguingly, the NIMA\u2010related kinase 2 (\n                      <jats:italic>NEK2<\/jats:italic>\n                      ) gene has been implicated in various cellular processes, but its role in cryptorchidism remains underexplored.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To elucidate NEK2's role, the researchers utilized NEK2 knockout mice, analyzing testes histology with hematoxylin\u2013eosin (HE) staining and assessing sperm morphology by Diff\u2010Quick staining. Immunohistofluorescence evaluated Leydig cell count, while Western blotting and immunohistochemistry analyzed 3\u03b2\u2010hydroxysteroid dehydrogenase 1 (HSD3B1), critical for testosterone synthesis. Mouse testosterone levels were quantified by ELISA, and RT\u2010qPCR examined testicular Wnt\u2013\u03b2\u2010catenin and HIPPO pathway expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      NEK2\u2010deficient mice exhibited significantly increased cryptorchidism incidence, decreased Leydig cell number, reduced testis\/body weights, and elevated sperm malformations. Histological analysis revealed pronounced testicular damage. Western blotting and immunohistochemistry showed unchanged nuclear receptor subfamily 5 (NR5A1) and insulin\u2010like protein 3 (INSL3), but decreased HSD3B1 in\n                      <jats:italic>NEK2<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice, leading to lower testosterone levels. Mechanistically, NEK2 knockout suppressed wingless\/integrated (Wnt)\u2013\u03b2\u2010catenin and activated HIPPO, causing mammalian sterile 20\u2010like protein kinase 2 (MST2)\u2013large tumor suppressor homolog 2 (LATS2)\u2010mediated downregulation of yes\u2010associated protein (YAP).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings highlight NEK2's essential role in regulating testicular descent and spermatogenesis, implicating it as a potential target for cryptorchidism.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bdr2.2485","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T06:42:56Z","timestamp":1747636976000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<i>NEK2<\/i>\n                    Contributes to the Protection Against Cryptorchidism Outcomes"],"prefix":"10.1002","volume":"117","author":[{"given":"Xiaomeng","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery Affiliated Hospital of Nantong University, Medical School of Nantong University  Nantong Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songyi","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Affiliated Hospital of Nantong University, Medical School of Nantong University  Nantong Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Affiliated Hospital of Nantong University, Medical School of Nantong University  Nantong Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirong","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of 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