| First Author | Bertoldo MJ | Year | 2016 |
| Journal | Mol Cell Endocrinol | Volume | 423 |
| Pages | 96-112 | PubMed ID | 26772142 |
| Mgi Jnum | J:237318 | Mgi Id | MGI:5811976 |
| Doi | 10.1016/j.mce.2016.01.001 | Citation | Bertoldo MJ, et al. (2016) Specific deletion of AMP-activated protein kinase (alpha1AMPK) in mouse Sertoli cells modifies germ cell quality. Mol Cell Endocrinol 423:96-112 |
| abstractText | The AMP-activated protein kinase (AMPK) is an important regulator of cellular energy homeostasis which plays a role in fertility. Complete disruption of the AMPK catalytic subunit alpha1 gene (alpha1AMPK KO) in male mice results in a decrease in litter size which is associated with the production of altered sperm morphology and motility. Because of the importance of Sertoli cells in the formation of germ cells, we have chosen to selectively disrupt alpha1AMPK only in the Sertoli cells in mice (Sc-alpha1AMPK-KO mice). Specific deletion of the alpha1AMPK gene in Sertoli cells resulted in a 25% reduction in male fertility associated with abnormal spermatozoa with a thin head. No clear alterations in testis morphology or modification in the number of Sertoli cells in vivo were observed, but a dysregulation in energy metabolism in Sertoli cells occurred. We have reported an increase in lactate production, in lipid droplets, and a reduction in ATP production in Sc-alpha1AMPK-KO Sertoli cells. These perturbations were associated with lower expression of mitochondrial markers (cytochrome c and PGC1-alpha). In addition another metabolic sensor, the deacetylase SIRT1, had a reduction in expression which is correlated with a decline in deacetylase activity. Finally, expression and localization of junctions forming the blood-testis barrier between Sertoli cells themselves and with germ cells were deregulated in Sc-alpha1AMPK-KO. In conclusion, these results suggest that dysregulation of the energy sensing machinery exclusively through disruption of alpha1AMPK in Sertoli cells translates to a reduction in the quality of germ cells and fertility. |
