biostudies-literatureTu Cthe national natural science foundation of Chinathe China Postdoctoral Science Foundation Funded Projectthe key grant of prevention and treatment of birth defect from Hunan provincenational key researchthe Hunan Provincial Natural Science Foundation of Chinathe national key research &amp; developmental program of China3848-3864https://www.ebi.ac.uk/biostudies/studies/S-EPMC8632297biostudies-literatureUnknown17(11)In humans, <i>TDRD7</i> (tudor domain containing 7) mutations lead to a syndrome combining congenital cataracts (CCs) and non-obstructive azoospermia (NOA), characterized by abnormal lens development and spermiogenesis. However, the molecular mechanism underlying TDRD7's functions in eye and testicular development are still largely unknown. Here, we show that the depletion of this gene in mice and humans resulted in the accumulation of autophagosomes and the disruption of macroautophagic/autophagic flux. The disrupted autophagic flux in <i>tdrd7-</i>deficient mouse embryonic fibroblasts (MEFs) was caused by a failure of autophagosome fusion with lysosomes. Furthermore, transcriptome analysis and biochemical assays showed that TDRD7 might directly bind to <i>Tbc1d20</i> mRNAs and downregulaAutophagyTDRD7 participates in lens development and spermiogenesis by mediating autophagosome maturation.PMC86322972019M66278681771645 and 819714472018YFC10049002019SK10122020JJ5993Li HTu CLi DLiu XLi WLi YLu GTan YQLin GMeng LWang WDu JWang YfalseTDRD7 participates in lens development and spermiogenesis by mediating autophagosome maturation.In humans, <i>TDRD7</i> (tudor domain containing 7) mutations lead to a syndrome combining congenital cataracts (CCs) and non-obstructive azoospermia (NOA), characterized by abnormal lens development and spermiogenesis. However, the molecular mechanism underlying TDRD7's functions in eye and testicular development are still largely unknown. Here, we show that the depletion of this gene in mice and humans resulted in the accumulation of autophagosomes and the disruption of macroautophagic/autophagic flux. The disrupted autophagic flux in <i>tdrd7-</i>deficient mouse embryonic fibroblasts (MEFs) was caused by a failure of autophagosome fusion with lysosomes. Furthermore, transcriptome analysis and biochemical assays showed that TDRD7 might directly bind to <i>Tbc1d20</i> mRNAs and downregula2021-01-01T00:00:00Z2021 Nov2025-05-29T21:24:15.632Z2025-05-29T21:24:15.632ZS-EPMC86322973361863210.1080/15548627.2021.1894058