In cattle, starting 4-5 days after estrus, pre-implantation embryonic development occurs in the confinement of the uterine lumen. Cells in the endometrial epithelial layer control the molecular traffic to and from the lumen and, thereby determine luminal composition. Starting early post-estrus, endometrial function is regulated by sex-steroids, but the effects of progesterone on luminal cells transcription have not been measured in vivo. First objective was to determine the extent to which progesterone controls transcription in luminal epithelial cells 4 d (D4) after estrus. Second objective was to discover luminal transcripts that predict pregnancy outcomes, when the effect of progesterone is controlled. Endometrial luminal epithelial cells were collected from embryo transfer recipients on D4 using a cytological brush and their transcriptome determined by RNASeq. Pregnancy by embryo transfer was measured on D30 (25 pregnant and 18 non-pregnant). Progesterone concentration on D4 was associated positively (n= 182) and negatively (n= 58) with gene expression. Progesterone-modulated transcription indicated an increase in oxidative phosphorylation, biosynthetic activity and proliferation of epithelial cells. When these effects of progesterone were controlled, different genes affected positively (n= 22) and negatively (n= 292) odds of pregnancy. These set of genes indicated that a receptive uterine environment was characterized by the inhibition of phosphoinositide signaling and innate immune system responses. A panel of 25 genes predicted the pregnancy outcome with sensitivity and specificity ranging from 64-96% and 44-83%, respectively. In conclusion, in the early diestrus, both progesterone-dependent and -independent mechanisms regulate luminal epithelial transcription associated with pregnancy outcomes in cattle.

Prior to implantation in cattle, the mucous medium contained in the uterine lumen serves as a working interface for molecular exchange and signaling between the lining endometrium and the embryo. The composition of this luminal fluid changes temporally according to the secretory and reabsorptive activities of the uterus and the embryo, which are under complex regulation. Via this interface, both the embryo and the endometrium reprogram each other's functions to support pregnancy continuation beyond the pre-implantation period. More specifically, the embryo receives elongation signals and the uterus receives anti-luteolytic stimuli. Here, characteristics of the luminal compartment as well as the regulation of its composition to determine the pregnancy outcome will be discussed.

No abstract

No abstract