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Selenium is an important trace element with a role in many aspects of human health, including male fertility. Determining its distribution at the cellular level in the body was difficult because of a lack of analytical techniques capable of imaging the element at high enough resolution. Now, US researchers have demonstrated that X-ray fluorescence microscopy (XFM) could be used to image selenium during sperm production providing clues regarding its role in infertility. In livestock and experimental rodents, researchers have observed that even moderate selenium deficiency can cause changes in sperm that cause breakages between head and tail or otherwise affect sperm motility. There is evidence that problems with selenium-containing proteins might be to blame. Other researchers have used radioactive selenium (selenium-75) to trace the element in sperm and initially found evidence that in the sperm mid-piece it is associated with a particular structural protein, "mitochondrial capsule selenoprotein". However, this result was later disproved, hinting at just how difficult it is to understand selenium biochemistry given that it shares several physical and chemical properties with sulfur, which is just above it in the periodic table. Another team finally identified phospholipid hydroperoxide glutathione peroxidase (GPx4 or PHGPX) as the selenoprotein in the sperm mid-piece, but even this work does not complete the selenium picture. Vadim Gladyshev formerly of the Redox Biology Center and Department of Biochemistry at the University of Nebraska, Lincoln, now at Harvard, and his colleagues at UNL, Argonne National Laboratory, and the NIH Laboratory of Cancer Prevention, in Bethesda, Maryland, reasoned that XFM might have high enough resolution to address a previously intractable problem. The team turned to the powerful microprobe on beamline 2-ID-E of the APS on which to carry out their experiments on the role of selenium in spermatogenesis. The team identified a significant rise in the concentration of selenium in late spermatids, an immature form of sperm, while levels of other elements monitored did not rise relative to other cells. They explain that the rise coincided with increased levels of the enzyme, mitochondrial GPx4, which is known to be essential for healthy sperm production. The formation of this enzyme, in turn, is dependent entirely on an adequate source of the selenium-containing protein, selenoprotein P, which is made in the liver and delivers selenium to the testes. The high-resolution XFM scans showed that selenium is most concentrated in elongating spermatids. This is where the structural components of the sperm form. The highest level of selenium was also associated with a reduction in phosphorus levels. The concentration of zinc, a trace metal often associated with male fertility did not change during this period. The XFM data also show that, in mature sperm, selenium is present mainly in the mid-piece region between sperm head and tail, where copper and iron are also abundant. 0.8 femtograms of selenium are present in the mid-piece and just 0.2 femtograms in the head of each sperm cell. This, the team explains, shows that sperm cells can cope with otherwise toxic levels of selenium. This research is the first to visualize, localize, and quantify the element selenium during sperm generation. It shows that the element accumulates during the development of immature sperm, so-called spermatids, through increased production of the mitochondrial form of phospholipid hydroperoxide glutathione peroxidase (mGPx4), which relies on a steady supply of selenium from the plasma selenoprotein, SelP. The team adds that, not only is the study important from the point of view of male fertility, the use of XFM could lead other researchers to insights into selenium trafficking and distribution in mammals. They suggest that as XFM matures still further, sensitivity and resolution will be improved, which will make it possible to track even lower concentrations of selenium than they observed in spermatids.
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XFM scan of a mouse seminiferous tubule |
