Genetic Polymorphism and mRNA Expression Studies Reveal IL6R and LEPR Gene Associations with Reproductive Traits in Chinese Holsteins

Genetic selection of milk yield traits alters the energy distribution of high producing cows, resulting in gene-induced negative energy balance, and consequently, poor body condition scores and reduced reproductive performances. Here, we investigated two metabolic-syndrome pathway genes, IL6R (Interleukin 6 receptor) and LEPR (Leptin receptor), for their polymorphism effects on reproductive performance in dairy cows, by applying polymorphism association analyses in 1588 Chinese Holstein cows (at population level) and gene expression analyses in granulosa cells isolated from eight cows (at cell level). Among the six single nucleotide polymorphisms we examined (two SNPs for IL6R and four SNPs for LEPR ), five were significantly associated with at least one reproductive trait, including female fertility traits covering both the ability to recycle after calving and the ability to conceive and keep pregnancy when inseminated properly, as well as calving traits. Notably, the identified variant SNP g.80143337A/C in LEPR is a missense variant. The role of IL6R and LEPR in cattle reproduction were further confirmed by observed differences in relative gene expression levels amongst granulosa cells with different developmental stages. Collectively, the functional validation of IL6R and LEPR performed in this study improved our understanding of cattle reproduction while providing important molecular markers for genetic selection of reproductive traits in high-yielding dairy cattle.