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Atp7a and Atp7b regulate copper homeostasis in developing male germ cells in mice
Metallomics ( IF 2.9 ) Pub Date : 2017-08-18 00:00:00 , DOI: 10.1039/c7mt00134g
Mateusz Ogórek 1, 2, 3, 4, 5 , Małgorzata Lenartowicz 1, 2, 3, 4, 5 , Rafał Starzyński 5, 6, 7, 8 , Aneta Jończy 5, 6, 7, 8 , Robert Staroń 5, 6, 7, 8 , Andrzej Doniec 1, 2, 3, 4, 5 , Wojciech Krzeptowski 2, 5, 9, 10, 11 , Aleksandra Bednarz 1, 2, 3, 4, 5 , Olga Pierzchała 1, 2, 3, 4, 5 , Paweł Lipiński 5, 6, 7, 8 , Zenon Rajfur 5, 10, 11, 12, 13 , Zbigniew Baster 5, 10, 11, 12, 13 , Patrycja Gibas-Tybur 5, 10, 11, 14, 15 , Paweł Grzmil 1, 2, 3, 4, 5
Affiliation  

The maintenance of copper homeostasis is critical for all cells. As learned from mice with disturbed copper metabolism, this trace element is also important for spermatogenesis. The experiments conducted in yeasts have demonstrated that appropriate copper level must be preserved to enable meiosis progression; however, increased copper level is toxic for cells. This study aims to analyze the expression profile of Atp7a and Atp7b and other genes encoding copper-related proteins during spermatogenesis in mice. Using the transcripts and protein detection techniques, we demonstrate that within seminiferous tubuli, ATP7A is mainly present in early meiotic germ cells (leptotene to pachytene spermatocytes) and in Sertoli cells (SCs). During spermatogenesis, the progression Atp7a expression profile corresponds to Slc31a1 (encoding copper importer CTR1) and Atox1 (encoding chaperon protein, which delivers copper from CTR1 to ATP7A and ATP7B) expression, suggesting that male germ cells retrieve copper and ATP7A protects them from copper overdose. In contrast, ATP7B protein is observed in SCs and near elongated spermatids; thus, its function seems to be related to copper extraction during spermiogenesis. This is the first study to give a comprehensive view on the activity of copper-related genes during spermatogenesis in mice.

中文翻译:

ATP7AATP7B调节体内铜平衡发展在小鼠雄性生殖细胞

铜稳态的维持对所有细胞都至关重要。正如从铜代谢紊乱的小鼠中学到的那样,这种微量元素对精子发生也很重要。在酵母中进行的实验表明,必须保持适当的铜水平,以使减数分裂进展。但是,铜水平升高对细胞有毒。本研究旨在分析的表达谱ATP7AATP7B在小鼠精子发生过程和编码铜相关蛋白的其他基因。使用转录本和蛋白质检测技术,我们证明了在生精小管中,ATP7A主要存在于早期减数分裂生殖细胞(瘦素至粗线精原细胞)和支持细胞(SCs)中。在精子发生过程中,Atp7a的进程其表达谱对应于Slc31a1(编码铜导入物CTR1)和Atox1(编码伴侣蛋白,其将铜从CTR1传递至ATP7A和ATP7B)的表达,这表明雄性生殖细胞可回收铜,而ATP7A可防止铜过量。相比之下,在SC和近乎细长的精子细胞中观察到ATP7B蛋白。因此,其功能似乎与精子发生过程中的铜提取有关。这是首次全面研究小鼠精子发生过程中铜相关基因活性的研究。
更新日期:2017-08-18
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