A defect in the peroxisomal biogenesis in germ cells induces a spermatogenic arrest at the round spermatid stage in mice.

Ann-Kristin Brauns, Markus Heine, Klaus Tödter, Eveline Baumgart-Vogt, Georg H Lüers, Udo Schumacher

Scientific reports 2019 Jul 02

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Peroxisomes are involved in the degradation of very long-chain fatty acids (VLCFAs) by β-oxidation. Besides neurological defects, peroxisomal dysfunction can also lead to testicular abnormalities. However, underlying alterations in the testes due to a peroxisomal defect are not well characterized yet. To maintain all metabolic functions, peroxisomes require an import machinery for the transport of matrix proteins. One component of this translocation machinery is PEX13. Its inactivation leads to a peroxisomal biogenesis defect. We have established a germ cell-specific KO of Pex13 to study the function of peroxisomes during spermatogenesis in mice. Exon 2 of floxed Pex13 was specifically excised in germ cells prior to meiosis by using a transgenic mouse strain carrying a STRA8 inducible Cre recombinase. Germ cell differentiation was interrupted at the round spermatid stage in Pex13 KO mice with formation of multinucleated giant cells (MNCs) and loss of mature spermatids. Due to a different cellular content in the germinal epithelium of Pex13 KO testes compared to control, whole testes biopsies were used for the analyses. Thus, differences in lipid composition and gene expression are only shown for whole testicular tissue but cannot be limited to single cells. Gas chromatography revealed an increase of shorter fatty acids and a decrease of n-6 docosapentaenoic acid (C22:5n-6) and n-3 docosahexaenoic acid (C22:6n-3), the main components of sperm plasma membranes. Representative genes of the metabolite transport and peroxisomal β-oxidation were strongly down-regulated. In addition, structural components of the blood-testis barrier (BTB) were altered. To conclude, defects in the peroxisomal compartment interfere with normal spermatogenesis.

Citation

Ann-Kristin Brauns, Markus Heine, Klaus Tödter, Eveline Baumgart-Vogt, Georg H Lüers, Udo Schumacher. A defect in the peroxisomal biogenesis in germ cells induces a spermatogenic arrest at the round spermatid stage in mice. Scientific reports. 2019 Jul 02;9(1):9553