Document Detail

Cell cycle regulation of human endometrial stromal cells during decidualization.
MedLine Citation:
PMID:  22534328     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Differentiation of endometrial stromal cells into decidual cells is crucial for optimal endometrial receptivity. Data from our previous microarray study implied that expression of many cell cycle regulators are changed during decidualization and inhibition of DNA methylation in vitro. In this study, we hypothesized that both the classic progestin treatment and DNA methylation inhibition would inhibit stromal cell proliferation and cell cycle transition.
METHODS: The human endometrial stromal cell line (HESC) was treated from 2 days to 18 days with the DNA methylation inhibitor, 5-aza-2'-deoxycytidine (AZA), a mixture of estradiol/progestin/cyclic adenosine monophosphate ([cAMP]; medroxy-progesterone acetate [MPA mix]) or both. Cell growth was measured by cell counting, cell cycle transition and apoptosis were analyzed by flow cytometry, expression of cell cycle regulators were analyzed by quantitative polymerase chain reaction (qPCR) and Western blotting, and change in DNA methylation profiles were detected by methylation-specific PCR.
RESULTS: Both AZA and MPA mix inhibited the proliferation of HESC for at least 7 days. Treatment with MPA mix resulted in an early G0/G1 inhibition followed by G2/M phase inhibition at 18 days. In contrast, AZA treatment inhibited cell cycle progression at the G2/M phase throughout. The protein levels of p21(Cip1)and 14-3-3σ were increased with both AZA and MPA mix treatments without any change in the DNA methylation profiles of the genes.
CONCLUSIONS: Our data imply that the decidualization of HESC is associated with cell cycle arrest at G0/G1 phase initially and G2/M phase at later stages. Our results also suggest that p53 pathway members play a role in the cell cycle regulation of endometrial stromal cells.
Philip C Logan; Michael Steiner; Anna P Ponnampalam; Murray D Mitchell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-24
Journal Detail:
Title:  Reproductive sciences (Thousand Oaks, Calif.)     Volume:  19     ISSN:  1933-7205     ISO Abbreviation:  Reprod Sci     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-24     Completed Date:  2012-12-03     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  101291249     Medline TA:  Reprod Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  883-94     Citation Subset:  IM    
The Liggins Institute, University of Auckland, Auckland, New Zealand.
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MeSH Terms
Azacitidine / analogs & derivatives,  pharmacology
Cell Cycle / physiology*
Cell Cycle Checkpoints / drug effects
Cell Cycle Proteins / genetics
Cell Line
Cyclic AMP / pharmacology
DNA Methylation / drug effects
Decidua / drug effects,  physiology*
Endometrium / physiology*
Estradiol / pharmacology
G0 Phase / drug effects
G1 Phase / drug effects
Gene Expression / drug effects
Medroxyprogesterone Acetate / pharmacology
Polymerase Chain Reaction
Progestins / pharmacology
Stromal Cells / physiology*
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Progestins; 320-67-2/Azacitidine; 50-28-2/Estradiol; 60-92-4/Cyclic AMP; 71-58-9/Medroxyprogesterone Acetate; 776B62CQ27/decitabine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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