Association of milk protein genes with fertilization rate and early embryonic development in Holstein dairy cattle.

Concomitant with intensive selection for increased milk yield, reproductive performance of dairy cows has declined in the last decades, in part due to an unfavourable genetic relationship between these traits. Given that the six main milk protein genes (i.e. whey proteins and caseins) are directly involved in milk production and hence have been a target of the strong selection aimed at improving milk yield in dairy cattle, we hypothesized that these genes could show selection footprints associated with fertility traits. In this study, we used an in-vitro fertilization (IVF) system to test genetic association between 66 single nucleotide polymorphisms (SNPs) in the four caseins (αS1-casein, αS2-casein, β-casein and κ-casein) and the two whey protein genes (α-lactalbumin and β-lactoglobulin) with fertilization rate and early embryonic development in the Holstein breed. A total of 6893 in-vitro fertilizations were performed and a total of 4661 IVF embryos were produced using oocytes from 399 ovaries and semen samples from 12 bulls. Associations between SNPs and fertility traits were analysed using a mixed linear model with genotype as fixed effect and ovary and bull as random effects. A multiple testing correction approach was used to account for the correlation between SNPs due to linkage disequilibrium. After correction, polymorphisms in the LALBA and LGB genes showed significant associations with fertilization success and blastocyst rate. No significant associations were detected between SNPs located in the casein region and IVF fertility traits. Although the molecular mechanisms underlying the association between whey protein genes and fertility have not yet been characterized, this study provides the first evidence of association between these genes and fertility traits. Furthermore, these results could shed light on the antagonistic relationship that exists between milk yield and fertility in dairy cattle.