Recurrent pregnancy loss (RPL) has significant emotional and financial impact on couples who are faced with infertility. RPL is believed to result from the inability of endometrial stromal cells to express an appropriate decidual phenotype (reviewed in Teklenburg et al., 2010), but the reasons for this are not clearly understood. MicroRNAs (miRNAs) are a class of small regulatory RNAs which modulate post-transcriptional translation. miRNAs have been shown to regulate a variety of biological processes and have been implicated in the establishment of pregnancy. Recently, miRNA mis-expression in endometrium from women who suffer from repeated implantation failure has been documented (Revel et al., 2011). Beyond this description and correlation with putative factors which may impact embryo implantation, little to no functional data nor an understanding on the mechanisms by which miRNAs regulate decidualization, have been presented? The objective of this exploratory pilot grant application is to examine the functional mechanisms by which miRNA mis-expression impairs stromal cell decidualization. In the proposed application, we will apply an innovative approach (RIP assay for miRNAs) to identify those mRNAs which are functionally regulated by miR- 27b during the process of decidualization. We anticipate that we will identify (and confirm) targets which are known to be essential for decidualization (such as HOXA10 and FOXO1) as well as novel, unforeseen targets. We will then examine the expression of these novel targets using a well-characterized mouse model of embryo implantation and decidualization gaining new insight into the mediators and mechanisms which are critical for successful pregnancy. The outcomes from this proposed research have the potential to provide novel insight into the role that specific miRNAs play in the process of decidualization. Ultimately this novel information will be applied to advance our understanding on recurrent pregnancy loss and develop new strategies towards correcting this clinical conundrum.
Recurrent pregnancy loss has major economical and emotional impact on women with this disease and is believed to result from the inability of endometrial stromal cells to express an appropriate decidual phenotype. To date, our understanding on the mechanisms which lead to the altered decidualization phenotype are poorly understood. The proposed studies will provide novel insight into the pathophysiology of recurrent pregnancy loss using an innovative approach to determine the functional role of microRNAs, which in turn will shed new light on the pathways which may be disturbed in the decidualization process in women who suffer from this disease.