Investigation on a role of Prx4 in spermatogenesis by gene knockout approach

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In this work, we investigated a role of Prx4, which is recently identified antioxidative protein, in spermatogenesis. Since Prx4 has signal sequence required for secretion from cells, it is assumed to function as an antioxidant in the extracellular milieu. However, it exists as a precursor form with the intact signal sequence in testes. We assume that Prx4 participates in spermatogenesis as judged by coincidental appearance of the precursor form during spermatogenic stage and by morphological analysis.At first, we investigated expression of Prx4 in artificial cryptorchid testes. Although there was no significant alteration in levels of the secreted form, the precursor form was selectively diminished. This result was consistent with the idea that the Prx4 precursor participates in spermatogenesis. Testes are generally in scrotum where temperature is lower in some degrees compared with other parts of body. This lower temperature is essential for normal spermatogenesis. In case of cryptor … More chidism, testes stay in peritoneal cavity and, hence, are exposed to higher temperature than normal testes. This causes impairment in spermatogenesis. However, it is not clear what kind of molecule is actually involved. Our results suggest elevation in activity of an enzyme that processes the Prx4 precursor. Abnormal elevation in activity of the processing enzyme would stimulate secretion of a protein, which induces apoptosis in testis, and result in the impairment. We are now trying to make mice that lack Prx4 gene.We further investigated glutathione redox system that plays a pivotal role in testes. We found that spermatogenic cells hardly synthesize glutathione because they exhibit quite low sensitivity to BSO, an inhibitor for de novo glutathione synthesis. In addition, they do not have recycling system for oxidized glutathione because glutathione reductase is not expressed. Based upon the gene expression, it appears that Sertoli cells reduce back the oxidized glutathione and provide it, together with other nutrition and humoral factors, to spermatogenic cells. Less