Decidualization of the endometrium is essential for successful pregnancy and in human
females of reproductive age, it occurs every month following the post-ovulatory rise in
progesterone levels. The decidualization of primary human endometrial stromal cells
(hESCs) can be recapitulated by treatment with cAMP and progestins, which results in
changes in gene expression that give rise to phenotypes that favour implantation and
survival of the conceptus. MicroRNAs (miRNAs) are a diverse class of small, non-coding
RNA molecules that regulate gene expression post-transcriptionally and have important
roles in many biological processes. Expression profiling revealed several miRNAs to be
regulated during decidualization, and alterations in miRNA pathway components were also
found. Although induction of Dicer suggested increased capacity to produce mature
miRNAs, endogenous miRNA silencing became restricted upon decidualization of hESCs
due to the down-regulation of the Argonaute proteins, catalytic components of the RNAinduced
silencing complex. This was reflected in the regulation of miRNA target genes,
which only appeared to be subject to miRNA-dependent regulation in undifferentiated
hESCs. Moreover, the regulation of the androgen receptor (AR), a nuclear hormone
receptor known to modulate the expression of a subset of decidual genes, was not
dependent on miRNAs during decidualization. Rather, an RNA binding protein, poly(C)-
binding protein 1 (PCBP1), regulated AR expression in hESCs during decidualization and
in LNCaP cells. Additionally, decidualizing hESCs export miRNAs in exosome-sized
vesicles that can be taken up by a variety of cells, including trophoblast and vascular cells,
representing a novel mode of communication that may coordinate responses across
different cell types at the feto-maternal interface.