{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T14:45:13Z","timestamp":1767624313944,"version":"3.41.2"},"reference-count":43,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32370905"],"award-info":[{"award-number":["32370905"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2024,9]]},"abstract":"Abstract<\/jats:title>Oligo\u2010astheno\u2010teratozoospermia (OAT) is a common cause of male infertility, but the genetic basis of most OAT cases is still unknown. Here, one homozygous loss\u2010of\u2010function (LOF) variant in TDRD6<\/jats:italic>, c.G1825T\/p.Gly609X, was identified in an infertile patient with severe OAT by whole\u2010exome sequencing (WES) and Sanger confirmation. Furthermore, Tdrd6<\/jats:italic>\u2010mutant mice (p.Gly615X; equivalent to p.Gly609X in human TDRD6<\/jats:italic>) were generated. Remarkably, the Tdrd6<\/jats:italic>\u2010mutated mice mimicked the severe OAT symptoms of the patient. In addition, the architecture of chromatoid bodies (CBs) were disrupted in round spermatids from Tdrd6<\/jats:italic>\u2010mutant mice, leading to blocked spermatogenesis in the round spermatids. The assembly of PIWIL1, TDRD1, TDRD7 and DDX25 in CBs was disturbed in the Tdrd6<\/jats:italic>\u2010mutant mice. Applying immunoprecipitation\u2010mass spectrometry (IP\u2010MS), we identified some TDRD6\u2010interacting partners, including CB proteins TDRD7, MAEL and PCBP1. Moreover, we described the assisted reproductive technology (ART) outcomes of the infertile patient and his partner. Altogether, our findings provide necessary evidences to support the idea that the homozygous LOF variant in TDRD6<\/jats:italic> induces male infertility with severe OAT, suggesting that TDRD6<\/jats:italic> could be a useful genetic diagnostic target for male infertility.<\/jats:p>","DOI":"10.1111\/jcmm.18580","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T17:33:10Z","timestamp":1727458390000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Loss\u2010of\u2010function variant in TDRD6<\/i> cause male infertility with severe oligo\u2010astheno\u2010teratozoospermia in human and mice"],"prefix":"10.1111","volume":"28","author":[{"given":"Xinying","family":"Bi","sequence":"first","affiliation":[{"name":"Center for Genetics National Research Institute for Family Planning Beijing China"},{"name":"Graduate School, Chinese Academy of Medical Sciences & Peking Union Medical College 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