Specific deletion of AMP-activated protein kinase (α1AMPK) in mouse Sertoli cells modifies germ cell quality
Specific deletion of AMP-activated protein kinase (α1AMPK) in mouse Sertoli cells modifies germ cell quality
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DOI：
10.1016/j.mce.2016.01.001
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发表时间：
2016-03-05
影响因子：
4.1
通讯作者：
Froment, Pascal
中科院分区：
文献类型：
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作者：
Bertoldo, Michael J.;Guibert, Edith;Froment, Pascal
AMP激活的蛋白激酶(AMPK)是细胞能量稳态的重要调节因子，在生育过程中起着重要作用。在雄性小鼠中，AMPK催化亚单位α1基因(α1AMPK KO)的完全破坏会导致产仔数减少，这与产生改变的精子形态和活力有关。由于支持细胞在生殖细胞形成中的重要性，我们选择选择性地阻断小鼠(SC-α1AMPK-KO小鼠)支持细胞中的α1AMPK。Sertoli细胞中α1AMPK基因的特异性缺失导致与头部细小的异常精子相关的男性生育力下降25%。体内睾丸形态未见明显改变，支持细胞数量无明显改变，但支持细胞能量代谢紊乱。我们已经报道了SC-α1AMPK-KO Sertoli细胞乳酸产生增加，脂滴增加，ATP产生减少。这些变化与线粒体标志物(细胞色素c和PGC1-α)的低表达有关。此外，另一种代谢感受器脱乙酰酶SIRT1的表达减少，这与脱乙酰酶活性下降有关。最后，在SC-α1AMPK-KO中，支持细胞之间以及与生殖细胞之间形成血-睾丸屏障的连接的表达和定位被解除调控。总而言之，这些结果表明，仅通过破坏支持细胞中的α1AMPK来调节能量感知机制的失调会导致生殖细胞质量和生育能力的下降。(C)2016爱思唯尔爱尔兰有限公司。保留所有权利。
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 alpha 1 gene (alpha 1AMPK 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 alpha 1AMPK only in the Sertoli cells in mice (Sc-alpha 1AMPK-KO mice). Specific deletion of the alpha 1AMPK 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-alpha 1AMPK-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-alpha 1AMPK-KO. In conclusion, these results suggest that dysregulation of the energy sensing machinery exclusively through disruption of alpha 1AMPK in Sertoli cells translates to a reduction in the quality of germ cells and fertility. (C) 2016 Elsevier Ireland Ltd. All rights reserved.