Effects of negative energy balance on liver gene and protein expression during the early postpartum period and its impacts on dairy cow fertility

Abstract

Negative energy balance (NEB) is a severe metabolic affecting high yielding dairy cows early post partum with both concurrent and latent negative effects on cow fertility as well as on milk production and cow health. The seasonal nature of Irish dairy production necessitates high cow fertility and a compact spring calving pattern in order to maximise grass utilisation. Poor dairy cow reproductive performance currently costs the Irish cattle industry in excess of €400 million annually. High milk yields have been associated with lower reproductive efficiency, and it has been suggested that this effect is probably mediated through its effects on the energy balance of the cow during lactation. The modern high genetic merit dairy cow prioritises nutrient supply towards milk production in early lactation and this demand takes precedence over the provision of optimal conditions for reproduction. In this study we used the bovine Affymetrix 23,000 gene microarray, which contains the most comprehensive set of bovine genes to be assembled and provides a means of investigating the modifying influences of energy balance on liver gene expression. Cows in severe negative energy balance (SNEB) in early lactation showed altered hepatic gene expression in metabolic processes as well as a down regulation of the insulin-like growth factor (IGF) system, where insulin like growth factor-1 (IGF-1), growth hormone receptor variant 1A (GHR1A) and insulin-like growth factor binding protein-acid labile subunit (IGFBP-ALS) were down regulated compared to the cows in the moderate negative energy balance MNEB group, consistent with a five-fold reduction in systemic concentrations of IGF1 in the SNEB group.Cows in SNEB showed elevated expression of key genes involved in the inflammatory response such as interleukin-8 (IL-8). There was a down regulation of genes involved in cellular growth in SNEB cows and moreover a negative regulator of cellular proliferation (HGFIN) was up regulated in SNEB cows, which is likely to compromise adaptation and recovery from NEB. The puma method of analysis revealed that 417 genes were differentially regulated by EB (P<0.05), of these genes 190 were up-regulated while 227 were down-regulated, with 405 genes having known biological functions. From Ingenuity Pathway Analysis (IPA), lipid catabolism was found to be the process most affected by differences in EB status.