Recently, we established an
in vitro
model with immortalized dog uterine stromal (DUS) cells for investigations into canine-specific decidualization. Their
capability to decidualize was assessed with cAMP and prostaglandin (PG) E2. Here, we show that the effects of PGE2 are mediated through both of the cAMP-mediating PGE2 receptors
(PTGER2/4). Their functional inhibition suppressed gene expression of
PRLR
and
PGR
in DUS cells. We also assessed the effects of cAMP and PGE2 on
selected extracellular matrix components and CX43, and showed that cAMP, but not PGE2, increases COL4, extracellular matrix protein 1 (ECM1) and CX43 protein levels during
in vitro
decidualization, indicating a mesenchymal-epithelial decidual transformation in these cells. Thus, although PGE2 is involved in decidualization, it does
not appear to regulate extracellular matrix. Further, the role of progesterone (P4) during
in vitro
decidualization was addressed. P4 upregulated
PRLR
and
PGR
in DUS cells, but these effects were not influenced by PGE2; both P4 and PGE2 hormones appeared to act independently. P4 did not
affect
IGF1
expression, which was upregulated by PGE2, however, it suppressed expression of
IGF2
, also in the presence of PGE2. Similarly, P4 did
not affect PGE2 synthase (
PTGES
), but in the presence of PGE2 it increased
PTGER2
levels and, regardless of the presence of PGE2, suppressed
expression of
PTGER4
. Our results indicate a reciprocal regulatory loop between PGE2 and P4 during canine
in vitro
decidualization: whereas P4 may
be involved in regulating PGE2-mediated decidualization by regulating the availability of its receptors, PGE2 regulates PGR levels in a manner dependent on PTGER2 and -4.