Atp7a and Atp7b regulate copper homeostasis in developing male germ cells in mice.

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.

A new TK model approach to assess the effect of migration on copper toxicokinetics in inbred populations of the flour beetle, Tribolium castaneum.

The aim of the study was to determine the influence of migration on copper (Cu) kinetics of male Tribolium castaneum after 25 generations of exposure for Cu-adapted and non-Cu-adapted inbred lines. Adapted lines were kept on a flour medium contaminated with 1000 mg Cu kg-1. A medium contaminated with 2000 mg Cu kg-1 of copper was used during the intoxication phase. Based on our data and literature reports, we introduced a new two-phase four-stage toxicokinetics (TK) model. The intoxication phase was successfully divided into three stages with separate assimilation rate constant (ka) and elimination rate constant (ke) values. The influence of migration was examined by comparing ka and ke parameters confidence intervals. In non-contaminated environments, migrants significantly increased ka and ke values in the second stage. Migrants decreased the maximum Cu accumulation observed in the experiment. The results indicated that the TK model must show high goodness-of-fit to be a useful tool for comparing treatments.