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Germline FOXJ2 overexpression causes male infertility via aberrant autophagy activation by LAMP2A upregulation
by
Wu, Qi-Qian
, Wu, Jing-Wen
, Cai, Chang
, Jiang, Zhi-Xuan
, Lv, Hao
, Wu, Yu-Jie
, Qian, Wen-Zhe
, Bai, Fu-Rong
, Hu, Yan-Qin
in
13/31
/ 13/44
/ 13/51
/ 14/28
/ 38/90
/ 38/91
/ 45/77
/ 631/136/2434/1822
/ 631/443/494/2732/1577
/ 64/60
/ Animals
/ Antibodies
/ Autophagy
/ Autophagy - genetics
/ Biochemistry
/ Biomedical and Life Sciences
/ Cell Biology
/ Cell Culture
/ Chromatin
/ Forkhead Transcription Factors - genetics
/ Forkhead Transcription Factors - metabolism
/ Germ cells
/ Heat shock proteins
/ Hsc70 protein
/ Humans
/ Immunology
/ Immunoprecipitation
/ Infertility
/ Infertility, Male - genetics
/ Infertility, Male - metabolism
/ Life Sciences
/ Lysosomal-Associated Membrane Protein 2 - metabolism
/ Lysosomes
/ Male
/ Meiosis
/ Membrane proteins
/ Mice
/ Spermatocytes
/ Spermatocytes - metabolism
/ Spermatogenesis
/ Spermatogenesis - genetics
/ Testes
/ Testis - metabolism
/ Up-Regulation
2022
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Germline FOXJ2 overexpression causes male infertility via aberrant autophagy activation by LAMP2A upregulation
by
Wu, Qi-Qian
, Wu, Jing-Wen
, Cai, Chang
, Jiang, Zhi-Xuan
, Lv, Hao
, Wu, Yu-Jie
, Qian, Wen-Zhe
, Bai, Fu-Rong
, Hu, Yan-Qin
in
13/31
/ 13/44
/ 13/51
/ 14/28
/ 38/90
/ 38/91
/ 45/77
/ 631/136/2434/1822
/ 631/443/494/2732/1577
/ 64/60
/ Animals
/ Antibodies
/ Autophagy
/ Autophagy - genetics
/ Biochemistry
/ Biomedical and Life Sciences
/ Cell Biology
/ Cell Culture
/ Chromatin
/ Forkhead Transcription Factors - genetics
/ Forkhead Transcription Factors - metabolism
/ Germ cells
/ Heat shock proteins
/ Hsc70 protein
/ Humans
/ Immunology
/ Immunoprecipitation
/ Infertility
/ Infertility, Male - genetics
/ Infertility, Male - metabolism
/ Life Sciences
/ Lysosomal-Associated Membrane Protein 2 - metabolism
/ Lysosomes
/ Male
/ Meiosis
/ Membrane proteins
/ Mice
/ Spermatocytes
/ Spermatocytes - metabolism
/ Spermatogenesis
/ Spermatogenesis - genetics
/ Testes
/ Testis - metabolism
/ Up-Regulation
2022
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Germline FOXJ2 overexpression causes male infertility via aberrant autophagy activation by LAMP2A upregulation
by
Wu, Qi-Qian
, Wu, Jing-Wen
, Cai, Chang
, Jiang, Zhi-Xuan
, Lv, Hao
, Wu, Yu-Jie
, Qian, Wen-Zhe
, Bai, Fu-Rong
, Hu, Yan-Qin
in
13/31
/ 13/44
/ 13/51
/ 14/28
/ 38/90
/ 38/91
/ 45/77
/ 631/136/2434/1822
/ 631/443/494/2732/1577
/ 64/60
/ Animals
/ Antibodies
/ Autophagy
/ Autophagy - genetics
/ Biochemistry
/ Biomedical and Life Sciences
/ Cell Biology
/ Cell Culture
/ Chromatin
/ Forkhead Transcription Factors - genetics
/ Forkhead Transcription Factors - metabolism
/ Germ cells
/ Heat shock proteins
/ Hsc70 protein
/ Humans
/ Immunology
/ Immunoprecipitation
/ Infertility
/ Infertility, Male - genetics
/ Infertility, Male - metabolism
/ Life Sciences
/ Lysosomal-Associated Membrane Protein 2 - metabolism
/ Lysosomes
/ Male
/ Meiosis
/ Membrane proteins
/ Mice
/ Spermatocytes
/ Spermatocytes - metabolism
/ Spermatogenesis
/ Spermatogenesis - genetics
/ Testes
/ Testis - metabolism
/ Up-Regulation
2022
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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.
Publisher
Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
Subject
/ 13/44
/ 13/51
/ 14/28
/ 38/90
/ 38/91
/ 45/77
/ 64/60
/ Animals
/ Biomedical and Life Sciences
/ Forkhead Transcription Factors - genetics
/ Forkhead Transcription Factors - metabolism
/ Humans
/ Infertility, Male - genetics
/ Infertility, Male - metabolism
/ Lysosomal-Associated Membrane Protein 2 - metabolism
/ Male
/ Meiosis
/ Mice
/ Testes
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