The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells

Logan, Philip C., Ponnampalam, Anna P., Rahnama, Fahimeh, Lobie, Peter E. and Mitchell, Murray D. (2010) The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Human Reproduction, 25 11: 2859-2869. doi:10.1093/humrep/deq238


Author Logan, Philip C.
Ponnampalam, Anna P.
Rahnama, Fahimeh
Lobie, Peter E.
Mitchell, Murray D.
Title The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells
Journal name Human Reproduction   Check publisher's open access policy
ISSN 0268-1161
1460-2350
1359-5911
Publication date 2010-11-01
Sub-type Article (original research)
DOI 10.1093/humrep/deq238
Volume 25
Issue 11
Start page 2859
End page 2869
Total pages 11
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted abstract
Background: Decidualization, the differentiation of endometrial stromal cells is a crucial step for successful implantation of an embryo, development of the placenta and completion of pregnancy to term. Epigenetic mechanisms are thought to be strongly involved in the regulation of processes controlling implantation, placentation, organ formation and foetal growth. Recent studies suggest that decreased DNA methylation facilitates a receptive endometrium. Hence, the aim of this project was to compare the transcriptional profile changes induced by the inhibitor of DNA methylation, 5-Aza-2′- deoxycytidine (AZA) to the transcriptional changes that happen during decidualization.

Methods and Results:
When DNA methylation was inhibited in a human endometrial stromal cell (HESC) line with AZA, it resulted in the fibroblast-like stromal cells being transformed into decidual-like morphology after 9 days. Expression of both prolactin and insulin-like growth factor binding protein-1, the two established decidualization marker genes, were minimally up-regulated by AZA after 10 days of treatment. In a microarray of a three-way experiment between AZA-treated and oestradiol/progestin/cAMP-treated [medroxy-progesterone acetate (MPA)-mix] HESC and the untreated controls, we detected more than 1000 common genes that had a significant difference of expression compared with the controls. AZA-treated cells in the microarray significantly expressed 76 genes in common with the MPA-mix treated cells, and AZA treatment also differentially regulated 148 genes independently to that of MPA-mix treatment. The MPA-mix regulated at least 36 genes in the cell adhesion, extracellular matrix remodelling and RhoGTPase cytoskeletal reorganization pathway; AZA regulated 19 of these genes in common and 15 other RhoGTPase pathway genes.

Conclusion: AZA induced some decidualization-like responses of endometrial stromal cells independently of progestins or cAMP, possibly via the cytoskeletal reorganization pathway of the RhoGTPase family. © 2010 The Author.
Keyword D?ecidualization
Endometrial stromal cell
Human endometrium
Epigenetic
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2011 Collection
 
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Created: Sun, 07 Nov 2010, 10:10:49 EST