| First Author | Li P | Year | 2022 |
| Journal | Biol Reprod | Volume | 107 |
| Issue | 5 | Pages | 1331-1344 |
| PubMed ID | 35980806 | Mgi Jnum | J:340896 |
| Mgi Id | MGI:7469694 | Doi | 10.1093/biolre/ioac162 |
| Citation | Li P, et al. (2022) CHD4 acts as a critical regulator in the survival of spermatogonial stem cells in mice. Biol Reprod 107(5):1331-1344 |
| abstractText | Spermatogenesis is sustained by homeostatic balance between the self-renewal and differentiation of spermatogonial stem cells, which is dependent on the strict regulation of transcription factor and chromatin modulator gene expression. Chromodomain helicase DNA-binding protein 4 is highly expressed in spermatogonial stem cells but roles in mouse spermatogenesis are not fully understood. Here, we report that the germ-cell-specific deletion of chromodomain helicase DNA-binding protein 4 resulted in complete infertility in male mice, with rapid loss of spermatogonial stem cells and excessive germ cell apoptosis. Chromodomain helicase DNA-binding protein 4-knockdown in cultured spermatogonial stem cells also promoted the expression of apoptosis-related genes and thereby activated the tumor necrosis factor signaling pathway. Mechanistically, chromodomain helicase DNA-binding protein 4 occupies the genomic regulatory region of key apoptosis-related genes, including Jun and Nfkb1. Together, our findings reveal the determinant role of chromodomain helicase DNA-binding protein 4 in spermatogonial stem cells survival in vivo, which will offer insight into the pathogenesis of male sterility and potential novel therapeutic targets. |
