An epigenetic disorder may cause aberrant expression of aromatase gene in endometriotic stromal cells.
OBJECTIVE
To examine the molecular basis of aromatase expression in stromal cell culture from endometriotic chocolate cysts.


METHODS
Prospective study.


METHODS
Department of Obstetrics and Gynecology and Department of Biosignaling, Tottori University, Yonago Japan.


METHODS
Thirty women, selected randomly, who underwent laparoscopy (n = 18) or laparotomy (n = 12).


METHODS
Endometrial and endometriotic stromal cells were obtained from the uterus and chocolate cyst lining of the ovary.


METHODS
Estradiol concentrations in the culture media were measured by means of enzyme immunoassay. Aromatase expression was examined by quantitative real-time polymerase chain reaction. Promoter usage was examined using unique exon I (PII, I.1, I.3, I.4, I.5, and I.6) and exon II primers. To determine the effect of 5-aza-deoxycytidine on endometrial stromal cells, the cells were treated with the agent for 96 hours.


RESULTS
Endometriotic cells secreted a marginal level of estradiol into the culture media, but adding testosterone to the culture produced a pronounced level of estradiol. In endometrial cells, estradiol production was far less efficient than in endometriotic cells even after adding testosterone. Real-time polymerase chain reaction analyses demonstrated the up-regulation of aromatase messenger RNA (mRNA) expression in endometriotic cells. Three proximal promoters, PII, 1.3, and 1.6, drove mRNA expression. In endometrial cells where a marginal level of aromatase mRNA expression was observed, the same promoters as those in the endometriotic cells were used. To determine the role of epigenetic modification of aromatase gene expression in endometriotic cells, endometrial cells were treated with 5-aza-deoxycytidine, which markedly enhanced aromatase mRNA expression, depending on the same proximal promoters as those in endometriotic cells.


CONCLUSIONS
An epigenetic disorder may play a role in the pathophysiology of endometriosis.
Department of Biosignaling, Tottori University School of Medicine, Yonago, Japan.
Masao
M
Izawa
Tasuku
T
Harada
Fuminori
F
Taniguchi
Yoko
Y
Ohama
Yasuko
Y
Takenaka
Naoki
N
Terakawa
D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D000077209:Decitabine; D004715:Endometriosis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D044127:Epigenesis, Genetic / Q000502:physiology*; D004958:Estradiol / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D010049:Ovarian Diseases / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D017154:Stromal Cells / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D014591:Uterine Diseases / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
D012333:RNA, Messenger; D004958:Estradiol; D000077209:Decitabine; D001141:Aromatase; D001374:Azacitidine