Changes in the endometrial transcriptome during the bovine estrous cycle: effect of low circulating progesterone and consequences for conceptus elongation

摘要

In cattle, elevated concentrations of circulating progesterone (P4) in theimmediate post-conception period have been associated with an advancement ofconceptus elongation, an associated increase in interferon-tau production and higherpregnancy rates. Low P4 has been implicated as a causative factor in the lowpregnancy rates observed in dairy cows. The aims of this study were (1) to describethe changes that occur in the bovine endometrial transcriptome during the estrouscycle, (2) to determine how elevated P4 affects the temporal pattern of geneexpression in the endometrium of cyclic heifers, (3) to determine if the expression ofthese genes is altered in heifers with low P4 and (4) to determine the consequences oflow P4 for conceptus development following embryo transfer. The main findingswere that 1) relatively few differences occurred in endometrial gene expression duringthe early luteal phase of the estrous cycle under normal concentrations of P4 (Day 5versus Day 7) but comparison of endometria from more distant stages of the lutealphase (Day 7 versus Day 13) revealed large transcriptional changes; 2) exogenoussupplementation of P4, leading to elevated concentrations from Day 3 to Day 8,considerably altered the expression of a large number of genes at all stages of theluteal phase; 3) induction of low circulating P4 altered the normal temporal changesthat occured in the expression of these genes, mainly by delaying their expression; 4)this delay in gene expression was, in part, due to delayed down regulation of thePGR from the LE and GE, and 5) the altered endometrial gene expression induced bylow P4 was associated with a reduced capacity of the uterus to support conceptusdevelopment after embryo transfer on Day 7. In conclusion, the present studyprovides clear evidence for a temporal change in the transcriptomic signature of thebovine endometrium which is sensitive to the concentrations of circulating P4 in thefirst few days after estrus and which can, under conditions of low progesterone, leadto an suboptimal uterine environment and a reduced ability to support conceptuselongation.