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

不孕不育是世界范围内的一个主要医学问题。大多数旨在阐明男性因素不育原因的研究都描述了单基因改变。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，我们通过使用两个世界范围内独特的小鼠模型（生育力系FL1和FL2）来改变观点，这两个模型被选择为参数“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增加了一倍，每窝总出生体重也增加了一倍。该项目的目的是初步表征这两个生育系的睾丸表型。表征包括评估睾丸的组织学组成，标记基因的表达，激素水平和经典的精子运动参数。全球基因表达分析将阐明受表型特征影响的分子途径。我们期望对睾丸实质的分子机制有新的基本认识，这对生殖结果有直接的影响。我们假设，那些为了维持较高的生育能力而受到影响的基因和途径，在其改变后也会导致“生育能力降低”的表型。为进一步研究男性因素性不育症的发病机制和治疗奠定基础。

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.