A Role for the orphan nuclear receptor estrogen-related receptor alpha in endometrial stromal cell decidualization and expression of genes implicated in energy metabolism.
BACKGROUND
Differentiation (decidualization) of endometrial stromal cells (ESC) is an essential prerequisite for successful implantation and establishment of pregnancy.


OBJECTIVE
The aim was to determine whether the orphan nuclear receptor estrogen-related receptor α (ERRα, NR3B1), and its target genes, medium chain specific acyl-CoA dehydrogenase (MCAD, ACADM), pyruvate dehydrogenase kinase 4 (PDK4), and phosphoenolpyruvate carboxykinase 2 (PEPCK, PCK2), play a role in the decidualization process.


METHODS
We conducted the study at a University Research Institute.


METHODS
Endometrial tissues were collected from women with regular menstrual cycles; tissues were used for recovery of primary ESC or RNA extraction or were fixed for immunohistochemistry. Primary ESC were decidualized in vitro; some cells were treated with XCT790 (ERRα inverse agonist).


RESULTS
Decidualization of ESC in vitro was associated with a significant increase in expression of transcripts encoding ERRα and its coactivator peroxisome proliferator-activated receptor γ coactivator-1 α. Expression of ERRα target genes was altered with increased expression of MCAD and PDK4 and reduced expression of PEPCK. Incubation of decidualized ESC with XCT790 reduced expression of ERRα and markers of decidualization such as IGFBP-1.


CONCLUSIONS
Increased expression of ERRα may play a role in altering the bioenergetics of decidualized ESC in preparation for implantation of the embryo and successful establishment of early pregnancy.
Bombail
Vincent
V
Medical Research Council Human Reproductive Sciences Unit, University of Edinburgh Centre for Reproductive Biology, The Queen's Medical Research Institute, Edinburgh, United Kingdom.
Gibson
Douglas A
DA
Collins
Frances
F
MacPherson
Sheila
S
Critchley
Hilary O D
HO
Saunders
Philippa T K
PT
D000328:Adult; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D003656:Decidua / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010064:Embryo Implantation / Q000187:drug effects / Q000235:genetics; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D009570:Nitriles / Q000494:pharmacology; D011247:Pregnancy; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013844:Thiazoles / Q000494:pharmacology; D000097983:ERRalpha Estrogen-Related Receptor
D006727:Hormone Antagonists; D009570:Nitriles; D011960:Receptors, Estrogen; D013844:Thiazoles; D000097983:ERRalpha Estrogen-Related Receptor; C488234:XCT790