DISEASE PROGRAMING OF ENDOMETRIAL REGENERATION AND FUNCTION IN POSTPARTUM DAIRY COWS

Our long-term goal is to improve fertility and thus productivity of dairy cows to increase profitability and sustainability of the dairy industry. Postpartum uterine disease is a widespread economic problem in the dairy industry and cows that experience uterine disease have reduced fertility postpartum. The short term-goal is to identify the cells that regenerate uterine glandular epithelium (GE) and luminal epithelium (LE) and determine how uterine disease reprograms these cells leading to infertility. We hypothesize that: (a) unique epithelial (stem/progenitor) cell populations reestablish the GE and LE within the first 30 d postpartum (dpp) and (b) the early postpartum period programs the embryotrophic capacity of these cells thus determining whether or not the cow can become pregnant later postpartum.Objective One will fill a significant gap in our scientific knowledge of uterine tissue regeneration and cell function during the first month postpartum. Studies are focused on determining which cells participate in the regeneration of the GE and LE and how uterine disease affects the regenerative process within the endometrium.Objective Two addresses the mechanisms through which early postpartum uterine disease programs infertility later postpartum. Studies are focused on determining the effects of early postpartum uterine disease on chromatin conformation and the transcriptome of endometrial cells during the breeding period when there is reduced embryotrophic capacity.Completion of the proposed objectives is expected to provide significant insight into how postpartum uterine disease affects endometrial cell regeneration and function, thereby programming uterine health and fertility in cows. This fundamental knowledge is necessary to develop innovative tools to restore fertility in currently diseased cows and guide genomic selection to prevent the disease in future cows.