Abstract
Dairy cows often experience a state of negative energy balance (NEB) during the first few months of lactation, resulting in dramatic fluctuations in circulating levels of hormones and metabolites that may have a negative impact on uterine environment and overall cow fertility. The objective of this study was to identify how the stage of lactation and energy status of the female impact gene expression in the endometrium during early pregnancy. Endometrial biopsies were collected on day 7 post-ovulation from Holstein heifers (n=3) and from lactating Holstein cows (n=22) at 54, 82, 137 days in milk (DIM). ß-hydroxybutyric acid and glucose levels were measured to determine the energy status of each cow as low, mild or severe NEB. RNA was extracted from each endometrial sample for relative transcript abundances of 34 genes involved in metabolism, heat shock/chaperone functions, and inflammatory response. Gene expression was evaluated by quantitative real-time PCR using the BioMark™ platform for gene expression analysis from Fluidigm. No changes were observed in the expression levels of heat shock protein/chaperone genes. Expression of inflammatory response genes IL-2, IL2RA, CD28, CTLA4, and GATA3 was significantly higher (adj. P < 0.05) in lactating cows when compared to heifers; among lactating animals, expression of IL-10, IL2RA, and CD28 was lower (P < 0.05) in cows with severe NEB. Expression of four genes involved in metabolism (ACACA, G6PD, IGF2R, and SLC16A3) was higher (P < 0.05) in heifers than in lactating cows, and expression of ACADL was lower (P < 0.05) in lactating cows around 130 DIM when most cows reached positive energy balance. We conclude from these data that lactation-and severe NEB-induced metabolic stress may result in a pro-inflammatory uterine environment that is inappropriately suited for supporting early embryo development and overall fertility in dairy cows.