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

In cattle, elevated concentrations of circulating progesterone (P4) in the
immediate post-conception period have been associated with an advancement of
conceptus elongation, an associated increase in interferon-tau production and higher
pregnancy rates. Low P4 has been implicated as a causative factor in the low
pregnancy rates observed in dairy cows. The aims of this study were (1) to describe
the changes that occur in the bovine endometrial transcriptome during the estrous
cycle, (2) to determine how elevated P4 affects the temporal pattern of gene
expression in the endometrium of cyclic heifers, (3) to determine if the expression of
these genes is altered in heifers with low P4 and (4) to determine the consequences of
low P4 for conceptus development following embryo transfer. The main findings
were that 1) relatively few differences occurred in endometrial gene expression during
the early luteal phase of the estrous cycle under normal concentrations of P4 (Day 5
versus Day 7) but comparison of endometria from more distant stages of the luteal
phase (Day 7 versus Day 13) revealed large transcriptional changes; 2) exogenous
supplementation 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 the
luteal phase; 3) induction of low circulating P4 altered the normal temporal changes
that 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 the
PGR from the LE and GE, and 5) the altered endometrial gene expression induced by
low P4 was associated with a reduced capacity of the uterus to support conceptus
development after embryo transfer on Day 7. In conclusion, the present study
provides clear evidence for a temporal change in the transcriptomic signature of the
bovine endometrium which is sensitive to the concentrations of circulating P4 in the
first few days after estrus and which can, under conditions of low progesterone, lead
to an suboptimal uterine environment and a reduced ability to support conceptus
elongation.