The mammalian testis-specific thioredoxin system

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The finding that four novel thioredoxins are either exclusively or predominantly expressed in testis is fascinating and opens a new area of research. Our current knowledge merely scratches the surface, and there are indeed more questions than answers regarding thioredoxin function in mammalian spermatogenesis. Clearly, the development of animal models will be the primary tool to elucidate the role of these proteins as no in vitro system has been established thus far, that would faithfully recapitulate spermatogenesis. Other approaches such as two-hybrid screening will also be useful to identify potential substrates and partners in FS, axoneme or spermatid manchette. There is also a strong need of deeper knowledge regarding the distribution and role of the cytosolic thioredoxin system during spermatogenesis, particularly TGR which bridges two of the major redox systems in the cell, the thioredoxin and the glutaredoxin systems. Redox regulation is a major issue in spermatogenesis and oxidative stress has been underpinned as a major causative factor of male infertility (2, 3). Defective sperm function has been associated with the retention of excess residual cytoplasm and increased free radical production by mechanisms that are poorly understood. We still do not know whether any of these spermatid-thioredoxins acts as antioxidant defense to counteract the overproduction of reactive oxygen species (ROS) in spermatozoa, though the conservation of the thioredoxin domain might indicate that this could indeed be the case in at least some of them. Other potential functions of the testis thioredoxin system might not even be anticipated. Such is the case of ubiquitin-dependent epididymal sperm quality control (96), since it was recently shown that Trx-1 functions as cofactor during protein ubiquitination (47). Clearly, the complete picture of the thioredoxin systems in the context of testis function is needed to determine why this class of proteins has become necessary for mammalian spermatogenesis, which has been regarded as the engine of evolution.