Abstract
BackgroundMany genes important for reproductive performance are shared by both sexes. However, fecundity indices are primarily based on female parameters such as litter size. We examined a fertility mouse line (FL2), which has a considerably increased number of offspring and a total litter weight of 180% compared to a randomly bred control line (Ctrl) after more than 170 generations of breeding. In the present study, we investigated whether there might be a parallel evolution in males after more than 40 years of breeding in this outbred mouse model.ResultsMales of the fertility mouse line FL2 showed reduced sperm motility performance in a 5 h thermal stress experiment and reduced birth rate in the outbred mouse line. Transcriptional analysis of the FL2 testis showed the differential expression of genes associated with steroid metabolic processes (Cyp1b1, Cyp19a1, Hsd3b6, and Cyp21a1) and female fecundity (Gdf9), accompanied by 150% elevated serum progesterone levels in the FL2 males. Cluster analysis revealed the downregulation of genes of the kallikrein-related peptidases (KLK) cluster located on chromosome 7 in addition to alterations in gene expression with serine peptidase activity, e.g., angiotensinogen (Agt), of the renin-angiotensin system essential for ovulation. Although a majority of functional annotations map to female reproduction and ovulation, these genes are differentially expressed in FL2 testis.ConclusionsThese data indicate that selection for primary female traits of increased litter size not only affects sperm characteristics but also manifests as transcriptional alterations of the male side likely with direct long-term consequences for the reproductive performance of the mouse line.
Highlights
Many genes important for reproductive performance are shared by both sexes
Animal model Studies in mice almost exclusively focus on a single gene approach using transgenic intervention in gain or lossof-function analyses
We changed the perspective by investigating a mouse model for the long-term selection of the primary female trait of high-fertility visible in increased litter size
Summary
Fecundity indices are primarily based on female parameters such as litter size. We examined a fertility mouse line (FL2), which has a considerably increased number of offspring and a total litter weight of 180% compared to a randomly bred control line (Ctrl) after more than 170 generations of breeding. Most knowledge concerning the interaction of genes has been obtained from exploratory models, such as transgenic or knockout mice. The database Mouse Genome Informatics (MGI - www.informatics.jax.org) harbors more than 2000 genotypes associated with reproductive phenotypes. The additional advantage of this approach is its heterogeneity, which more closely mimics the phenotypic alterations in nature compared to single gene approaches to generate classical transgenic or knockout models
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