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Stem Cell Reports ; 13(3): 559-571, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31402338

RESUMO

Development of spermatogonia and spermatocytes are the critical steps of spermatogenesis, impacting on male fertility. Investigation of the related regulators benefits the understanding of male reproduction. The proteasome system has been reported to regulate spermatogenesis, but the mechanisms and key contributing factors in vivo are poorly explored. Here we found that ablation of REGγ, a proteasome activator, resulted in male subfertility. Analysis of the mouse testes after birth showed there was a decreased number of PLZF+ spermatogonia and spermatocytes. Molecular analysis found that REGγ loss significantly increased the abundance of p53 protein in the testis, and directly repressed PLZF transcription in cell lines. Of note, allelic p53 haplodeficiency partially rescued the defects in spermatogenesis observed in REGγ-deficient mice. In summary, our results identify REGγ-p53-PLZF to be a critical pathway that regulates spermatogenesis and establishes a new molecular link between the proteasome system and male reproduction.


Assuntos
Autoantígenos/metabolismo , Proteína com Dedos de Zinco da Leucemia Promielocítica/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Espermatogênese , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose , Autoantígenos/genética , Masculino , Meiose , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oligonucleotídeos Antissenso , Regiões Promotoras Genéticas , Proteína com Dedos de Zinco da Leucemia Promielocítica/antagonistas & inibidores , Proteína com Dedos de Zinco da Leucemia Promielocítica/genética , Complexo de Endopeptidases do Proteassoma/deficiência , Complexo de Endopeptidases do Proteassoma/genética , Ligação Proteica , Transdução de Sinais , Motilidade dos Espermatozoides , Espermatócitos/citologia , Espermatócitos/metabolismo , Espermatogônias/citologia , Espermatogônias/metabolismo , Testículo/metabolismo , Proteína Supressora de Tumor p53/genética
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