Male fertility phenotypes: Characterization of two high fertility outbreed mouse lines to explore male factor (in)fertility.

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Infertility is a major medical problem worldwide. Most of the studies conducted to elucidate reasons for male factor infertility described single gene alterations. However, this does not reflect reality in most infertile patients. Infertility rather appears to be a complex, multi-causal phenomenon. In the present study we therefore change the perspective by using two worldwide unique mouse models (fertility lines FL1 and FL2) which were selected for the parameter "high fertility" for more than 150 generations. These mice almost doubled the number of offspring as well as they doubled the total birth weight per litter in comparison to a control line. The aim of this project is to initially characterize the testicular phenotypes of these two fertility lines. The characterization includes evaluation of the histological composition of the testis, expression of marker genes, hormone levels and classical sperm motility parameters. A global gene expression analysis will elucidate the molecular pathways affected by the phenotypic characteristics.We expect to gain new basic insights into molecular mechanisms within the testicular parenchyma which have a direct impact on the reproductive outcome.We hypothesise that those genes and pathways which are affected in order to maintain a higher fertility also contribute to the phenotype "reduced fertility" upon their alteration.Therefore, with this project we build the basis for future investigations concerning pathogenesis and therapy of male factor infertility.