Department of Genetics and Evolution, Institute of Zoology and Biomedical Research, Jagiellonian University Kraków, Gronostajowa 9, 30-387 Kraków, Poland.
Metallomics. 2017 Sep 20;9(9):1288-1303. doi: 10.1039/c7mt00134g.
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.
铜稳态的维持对所有细胞都至关重要。从铜代谢紊乱的小鼠实验中得知，这种微量元素对精子发生也很重要。酵母实验表明，必须保持适当的铜水平以促进减数分裂的进行；然而，铜水平的增加对细胞是有毒的。本研究旨在分析铜相关蛋白基因 Atp7a 和 Atp7b 以及其他基因在小鼠精子发生过程中的表达谱。使用转录本和蛋白质检测技术，我们证明在精小管内，ATP7A 主要存在于早期减数分裂的生殖细胞（细线期到粗线期精母细胞）和支持细胞（SCs）中。在精子发生过程中，Atp7a 表达谱的进展与 Slc31a1（编码铜导入器 CTR1）和 Atox1（编码伴侣蛋白，将铜从 CTR1 传递给 ATP7A 和 ATP7B）的表达相对应，表明雄性生殖细胞回收铜，ATP7A 保护它们免受铜过量的影响。相反，ATP7B 蛋白在 SCs 和伸长的精子中观察到；因此，其功能似乎与精子发生过程中的铜提取有关。这是首次对小鼠精子发生过程中铜相关基因活性进行全面研究。
