Endometrial gene expression in high- and low-fertility heifers in the late luteal phase of the estrous cycle and a comparison with midluteal gene expression

Embryonic mortality is a major constraint to improving reproductive efficiency and profitability in livestock enterprises. We previously reported differential expression of genes with identified roles in cellular growth and proliferation, lipid metabolism, endometrial remodeling, inflammation, angiogenesis, and metabolic exchange in endometrial tissue on day 7 of the estrous cycle (D7), between heifers ranked as either high (HF) or low (LF) for fertility. The aim of the current study was to further elucidate the underlying molecular mechanisms contributing to early embryo loss by examining differential endometrial gene expression in HF or LF heifers at a later stage of the estrous cycle; day 14 (D14). A second objective was to compare these expression profiles with those from midluteal HF and LF endometrium. Using the same animal model as employed in the previous study, we slaughtered HF and LF animals on D14, harvested endometrial tissue, and carried out global gene expression analysis using the Affymetrix Bovine GeneChip. Microarray analysis detected 430 differentially expressed genes (DEG) between HF and LF animals. Ingenuity Pathway Analysis revealed enrichment for a host of biological pathways including lipid metabolism, molecular transport, immune response, cell morphology and development, and cell growth and proliferation. Important DEG included ALB, BMPR2, CCL28, COL4A3/4, FADS1, ITGA6, LDLR, PLCB3, PPARG, PTGS2, and SLC27A4. Furthermore, DEG expressed on both D7 and D14 included: PCCB, SLC25A24, DAP, and COL4A4. This study highlights some of the pathways and mechanisms underpinning late luteal bovine endometrial physiology and endometrial-related conception rate variance.