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Title: The role of microRNAs in the endometrium
Author: Shah, Kunal Mukesh
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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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.
Supervisor: Christian, Mark ; Dibb, Nick Sponsor: Biotechnology and Biological Sciences Research Council ; Genesis Research Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available