Selection for female traits of high fertility affects male reproductive performance and alters the testicular transcriptional profile

Abstract

Background: Many 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. Results: Males 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. Conclusions: These 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.