Application: Reproductive ageing is associated with decline in fertility in mammals. Considering the irreplaceable contribution of the uterus to pregnancy success and outcomes, determining the impact of ageing on this organ is essential to identify strategies that preserve its biological functions in older females. Introduction: Ageing is associated with an inflammatory process that affects the functions of most organs. Although age-related dysfunction of cell cycle and activation of inflammation-related pathways has been reported in bovine uterus, effect of ageing on endometrial physiology remains a matter of debate in cattle and more generally in mammals. Using an experimental model of cloned bovine females, the objective of our study was to evaluate the effect of ageing on the endometrium using transcriptome profiles patterns and the responses of cultured endometrial cells to interferon tau, the major factor of pregnancy recognition in ruminants. Materials and Methods: The study was conducted using 6 young primiparous bovine clones aged 4–5 years and 7 old nulliparous clones aged 13–14 years generated from the same somatic cell line and reared under similar conditions. Plasma progesterone concentration was determined at days 2, 8, 14, and 22 post-estrus cycle synchronization. Using endometrial biopsies and a custom bovine array (23,926 unique transcripts), gene expression profiles were determined in four individuals per group at 15 days post-estrus. Differentially expressed genes were identified using the fold change rank ordering method. Pathway enrichment analyses were performed using Ingenuity Pathway Analysis software. Primary cultures of endometrial cells were derived from biopsies collected at 15 days post-estrus (n = 3/ group) then incubated with recombinant interferon-tau (IFNT, 100 ng/mL) for 1 h and 24 h. Transcript levels of interferon- dependent genes were quantified by RT-qPCR. Results: Progesterone profiles were similar between the two groups of females. Between young and old bovine endometrium, transcriptome analyses unveiled 1286 differentially expressed genes, and activation of pathways related to inflammation, immunity, metabolism, and cellular processes. In primary glandular epithelial cells treated with rIFNT for 1 h, MX1 and RSAD2 transcript levels were significantly lower in old versus young bovine females (P-value 0,01 and P-value 0,05 respectively). In stromal cells, RSAD2 transcript level was significantly lower in old females at 1 h (P-value 0,001). Conclusions: By affecting the ability of the endometrium to respond to the embryo, we suggest that age-related modifications of endometrial physiology may account for reproductive failures of uterine origin. Additional experiments are required to support our hypothesis.