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

不孕症是世界范围内的主要医学问题。大多数的研究进行，以阐明男性因素不育的原因描述单基因改变。然而，这并不能反映大多数不孕症患者的实际情况。不孕症似乎是一个复杂的，多原因的现象。因此，在本研究中，我们通过使用两种全球独特的小鼠模型（生育力系FL1和FL2）来改变观点，这两种小鼠模型被选择用于参数“高生育力”超过150代。与对照组相比，这些小鼠的后代数量几乎翻了一番，每窝总出生体重也翻了一番。该项目的目的是初步表征这两个生育系的睾丸表型。表征包括评价睾丸的组织学组成、标记基因的表达、激素水平和经典的精子运动参数。全面的基因表达分析将阐明受表型特征影响的分子途径。我们期望获得对睾丸实质内直接影响生殖结果的分子机制的新的基本见解。我们假设那些受影响以维持较高生育力的基因和途径也有助于表型“生育力降低”。因此，本研究为进一步探讨男性因素不育的发病机制及治疗奠定了基础。

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.