Systems approach to deciphering molecular mechanisms of infertility in lactating dairy cows with subclinical ketosis

Reproductive failure is the number one cause of voluntary culling in Canadian dairy herds. More than 60% of cows do not make it to their third or higher lactation. This is an enormous burden on the farm profitability as a cow becomes profitable only during her third lactation. Therefore, understanding the mechanisms of reproductive failure due to ovarian dysfunction is important to develop diagnostic, therapeutic and managemental strategies to optimize reproductive performance of lactating dairy cows. It is well established that metabolic stress that the cows experience during early lactation impacts on reproductive processes. Subclinical ketosis is the most prevalent metabolic disorder in dairy herds. Therefore, the objective of this project are: 1) To profile the metabolic indicators in the serum and milk of healthy, type I and type II subclinical ketosis cows; 2) To profile the transcriptome of the liver in healthy, type I and type II subclinical ketosis cows using RNAsequencing technology; and 3) To determine granulosa cell transcriptome of the dominant follicle of the healthy, type I and type II ketosis cows. These objectives are based on our preliminary results showing that metabolically stressed lactating cows have altered gene expression in the liver with associated ovarian dysfunction. We propose to use systems approach employing RNA sequencing technology to investigate the liver and ovarian functions in healthy and ketosis cows. Other molecular biology techniques including quantitative PCR, plasma biochemistry, on farm data including production and nutritional data will be used to complement our transcriptome data. Overall, the results of this project will enhance our understanding of the impact of metabolic disorders like ketosis on ovarian functions and thus lactating cow fertility.