Molecular mechanism of male infertility caused by arrest of spermatogenesis

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More than 90% of the glycolipid in mammalian testis consists of a unique sulfated glyceroglycolipid, seminolipid. Seminolipid is synthesizedby sequential action of the two enzymes, ceramide galactosyltransferase (CGT) and GalCer sulfotransferase (CST). Disruption of the Cgt and/or Cst gene in mice results in male infertility due to the an est of spermatogenesis prior to the metaphase of the first meiosis. This observation provided the first experimental evidence that seminolipid is essential for normal spermatogenesis. Lb clarify the process and mechanism of germ cell degeneration in the absence of seminolipid, testicular proteins were separated by two-dimensional electrophoresis. The resulting gel images were compared between the wild-type and CGT-deficient mice at the age of 7, 10, 13 and 16 days, around which biosynthesis of seminolipid begins in the wild-type testis. A protein spot was increased in the testis of CGT-deficient mice at the age of 10, 13 and 16 days. By in-gel proteolysis followed by MALDI-TOFMS, the spot was identified as vimentin In addition, by specific detection for phosphoproteins, several spots were increased or decreased in the testis of CGT-deficient mice. It was reported that germ cell differentiation may be mediated by surface interactions between germ cells and Sertoli cells through cell junctions and the junction restructuring is regulated by various signaling molecules. It was also known that vimentin is a protein component of desmosome, which is a type of cell junctions between germ cells and Sertoli cells. Because seminolipid is expressed on the cell surface of primary spermatocytes, it was suggested that the lack of seminolipid may result in disruption of Sertoli-germ cell interactions via dysfunction of the cell junction.