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Germline FOXJ2 overexpression causes male infertility via aberrant autophagy activation by LAMP2A upregulation
Germline FOXJ2 overexpression causes male infertility via aberrant autophagy activation by LAMP2A upregulation
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Germline FOXJ2 overexpression causes male infertility via aberrant autophagy activation by LAMP2A upregulation
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Germline FOXJ2 overexpression causes male infertility via aberrant autophagy activation by LAMP2A upregulation
Germline FOXJ2 overexpression causes male infertility via aberrant autophagy activation by LAMP2A upregulation

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Germline FOXJ2 overexpression causes male infertility via aberrant autophagy activation by LAMP2A upregulation
Germline FOXJ2 overexpression causes male infertility via aberrant autophagy activation by LAMP2A upregulation
Journal Article

Germline FOXJ2 overexpression causes male infertility via aberrant autophagy activation by LAMP2A upregulation

2022
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Overview
Spermatogenesis is a complex biological process that produces haploid spermatozoa and requires precise regulation by many tissue-specific factors. In this study, we explored the role and mechanism of Fork head box J2 (FOXJ2, which is highly expressed in spermatocytes) in the regulation of spermatogenesis using a germline-specific conditional Foxj2 knock-in mouse model ( Stra8-Cre; Foxj2 tg/tg mouse). Foxj2 overexpression in mouse testes led to spermatogenesis failure, which started at the initiation of meiosis, and resulted in male infertility. Lysosomes and autophagy-related genes were upregulated in Stra8-cre; Foxj2 tg/tg mouse testes and the number of autolysosomes in the spermatocytes in Stra8-cre; Foxj2 tg/tg mice was increased. Chromatin immunoprecipitation-PCR and Dual-luciferase reporter assays showed that Lamp2 (encoding lysosome‐associated membrane protein‐2) was a target of FOXJ2. Foxj2 overexpression increased the expression levels of Lamp2a and Hsc70 (70-kDa cytoplasmic heat shock protein) in the Stra8-cre; Foxj2 tg/tg mouse testes. Our results suggested that Foxj2 overexpression in the germ cells of mouse testes affects chaperone-mediated autophagy by upregulating LAMP2A, leading to spermatogenesis failure at the initiation of meiosis, thus resulting in male infertility. Our findings provide a new insight into the function of FOXJ2 in spermatogenesis and the significance of autophagy regulation in spermatogenesis.