RE08 : Epigenetic study for the phatalate and uterine leiomyoma

Objective: Studies on leiomyoma of uterus and phthalates, one of the estrogen-dependent diseases, have shown equivocal results. However, in our case-control study, phthalate exposure in patients with uterine leiomyoma was found to be higher than in the control group. Therefore we want to know if there is the correlation with phthalates exposure and epigenetic changes on the pathology of uterine myoma. Methods: We obtained tissues(endometrium, myometrium and leiomyoma) from the paients who had undergone hysterectomy, myomectomy or laparotomy with uterine leiomyoma and without uterine leiomyoma. Concentrations of phthalate metabolites were determined by liquid chromatography-tandem mass spectrometry. In the case of urine, the measured concentration was corrected by urine creatinine concentration. Using the Pyrosequencing and MethyLight assays, we analyzed promoter methylation levels of ER, PR, and aromatase genes associated with myoma and global DNA methylation using repetitive elements (LINE1, Sat2 Alu). Results: 1. DNA methylation at the promoter region of the estrogen receptor alpha (ERalpha) gene and progesterone receptor gene in human endometrium (n = 30), myoma (n = 21) and adenomyosis The association of exposure was first identified.2. Phthalate exposure (MEHP, MMP) in endometrial tissues appears to have a significant negative correlation with ER a methylation.3. Significant negative correlation between ERα methylation and phthalate exposure (MEOHP, MEHHP, 2cx-MMHP, 5cx-MEPP, ΣMEHP-3 and ΣMEHP-3) negative correlation was confirmed. Conclusion: In this study, hypomethylation of DNA in the promoter region of estrogen receptor alpha (ERalpha) gene of human endometrium, uterine leiomyoma and uterine leiomyoma was observed with more phthlate exposure. However, it is difficult to understand pathophysiology with too few specimens, so more research is needed.