Impact of peroxisomal metabolism in germ and Leydig cells on overall testis functions and male fertility

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Human disorders with peroxisomal deficiency show a range of testicular pathologies leading to male infertility, the molecular pathogenesis of which is not yet understood. We have therefore characterised peroxisomes and identified a strong heterogeneity of peroxisomal protein composition in distinct cell types of mouse and human testis and revealed that Sertoli cell peroxisomes are essential for the maintenance of regular spermatogenesis and the overall regulation of gonadal steroid metabolism. Since the impact of peroxisomal metabolism of germ and Leydig cells on overall testicular functions is not yet understood, we will establish PEX13KO-mouse models with peroxisome deficiency to investigate the relevance of peroxisomal metabolism 1) in spermatogonia and spermatids for germ cell differentiation and for male fertility, and 2) in Leydig cells for androgen synthesis, paracrine and endocrine control of testicular functions. The phenotypic analyses will include the histopathological characterisation of testis samples, analysis of marker enzymes, biochemical measurements of steroids and other peroxisome-related metabolites, mRNAexpression profiling and in vitro studies on organotypic and primary cell cultures. 3) Important results will be transferred to the analyses of human testis and blood samples.