Differential gene expression in the endometrium reveals cytoskeletal and immunological genes in lactating dairy cows genetically divergent for fertility traits

Profitable milk production in dairy cows requires good reproductive performance. Calving interval is a trait used to measure reproductive efficiency. Here we used a novel lactating Holstein cow model of fertility that displayed genetic and phenotypic divergence in calving interval, a trait used to define reproductive performance using a national breeding index in Ireland. Cows had similar genetic merit for milk production traits, but either very good genetic merit for fertility (Fert+; n = 7) or very poor genetic merit for fertility (Fert-; n = 6). We tested the hypothesis that Fert+ cows would have a corresponding detectable difference in endometrial gene expression compared to the Fert- cows. To do this, we sequenced the transcriptome of endometrial biopsies collected on day 7 of the estrous cycle (non-pregnant). This is an important stage for uterine remodelling and initiation of histotroph secretion. Significant differential expression (FDR adjusted p < 0.1) of 403 genes between Fert+ and Fert- cows was found. A novel network-based functional analysis highlighted 123 genes from 3 physiologically relevant networks of the endometrium: actin and cytoskeletal components; immune function, and ion transportation. In particular, our results indicated an overall down-regulation of inflammation-related genes and an up-regulation of multiple ion transporters and gated-voltage channels and cytoskeletal genes in Fert+ cows. These three topics, which are discussed in terms of the uterus and in the context of fertility, provide molecular evidence for an association of gene expression in the uterine environment with genetic merit for fertility in dairy cows.