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Leopold Floh
Selenium in mammalian spermiogenesis
Keywords: male fertility, moonlighting protein, phospholipid hydroperoxide glutathione peroxidase (GPx4), selenium, selenoproteins, spermatogenesis
The role of the trace element selenium in maintaining male fertility is reviewed with special
emphasis on the importance of selenoprotein P and GPx4 in spermiogenesis. Inverse genetics
reveal that selenoprotein P is required to assure an adequate selenium supply of testis. GPx4 is
abundantly synthesized in spermatids. As moonlighting protein it is transformed at later stages
of spermiogenesis from an active selenoperoxidase into a structural protein that becomes an
indispensable constituent of the mitochondrial sheath in the mid piece of spermatozoa. The
transformation is paralleled by, and depends on, loss of GSH. Mechanistically, the process is
interpreted as alternate substrate inactivation of GPx4 resulting from reactions of the oxidized
enzyme (selenenic form) with thiols of GPx4 itself and other proteins. Circumstantial evidence
and ongoing experimental genetics indicate that the mitochondrial expression form of the
GPx4 gene is the most abundant and relevant one, the nuclear form proved to be dispensable
for fertility, and the role of cytosolic GPx4 in spermiogenesis remains unclear, since targeted
gene disruption was lethal. Clinical data reveals a strong association of low GPx4 in sperm
with infertility. Thus, impaired GPx4 biosynthesis, which may be due to selenium deficiency
or genetic defects in
Biological Chemistry, Walter de Gruyter
Print ISSN: 1431-6730
Volume: 2007
Pages: -