Decidual stromal cells differentiate from endometrial stromal
fibroblasts (ESFs) under the influence of progesterone and cyclic
adenosine monophosphate (cAMP) and are essential for implantation and
the maintenance of pregnancy. They evolved in the stem lineage of
placental (eutherian) mammals coincidental with the evolution of
implantation. Here we use the well-established in vitro decidualization
protocol to compare early (3 days) and late (8 days) gene transcription
patterns in immortalized human ESF. We document extensive, dynamic
changes in the early and late decidual cell transcriptomes. The data
suggest the existence of an early signal transducer and activator of
transcription (STAT) pathway dominated state and a later nuclear factor
κB (NFKB) pathway regulated state. Transcription factor expression in
both phases is characterized by putative or known progesterone receptor (PGR)
target genes, suggesting that both phases are under progesterone
control. Decidualization leads to proliferative quiescence, which is
reversible by progesterone withdrawal after 3 days but to a lesser
extent after 8 days of decidualization. In contrast, progesterone
withdrawal induces cell death at comparable levels after short or long
exposure to progestins and cAMP. We conclude that decidualization is
characterized by a biphasic gene expression dynamic that likely
corresponds to different phases in the establishment of the
fetal–maternal interface.