In:
Cell Death & Disease, Springer Science and Business Media LLC, Vol. 13, No. 7 ( 2022-07-30)
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
2041-4889
DOI:
10.1038/s41419-022-05116-w
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2022
ZDB Id:
2541626-1
