PMID- 30728052 OWN - NLM STAT- MEDLINE DCOM- 20190501 LR - 20210816 IS - 1757-2215 (Electronic) IS - 1757-2215 (Linking) VI - 12 IP - 1 DP - 2019 Feb 6 TI - Aberrant DNA methylation suppresses expression of estrogen receptor 1 (ESR1) in ovarian endometrioma. PG - 14 LID - 10.1186/s13048-019-0489-1 [doi] LID - 14 AB - BACKGROUND: In ovarian endometriomas (OE), the expression statuses of various steroid hormone receptors are altered compared with their expression statuses in eutopic endometrium (EE). For example, in OE, the expressions of estrogen receptor 1 (ESR1), which encodes ERalpha, and progesterone receptor (PGR) are downregulated, while the expression of ESR2, which encodes ERbeta, is upregulated. The causes of these changes are unclear. DNA methylation of a specific region of a gene can result in tissue-specific gene expression. Such regions are called tissue-dependent and differentially methylated regions (T-DMRs). We previously reported that the tissue-specific expression of ESR1 is regulated by DNA methylation of a T-DMR in normal tissues. In the present study, we examined whether aberrant DNA methylation of the T-DMR is associated with the altered expressions of ESR1, ESR2 and PGR in OE. RESULTS: Gene expression levels of ESR1, ESR2 and PGR were measured by quantitative RT-PCR. The expression levels of ESR1 and PGR were significantly lower and the expression level of ESR2 was significantly higher in OE than in EE. DNA methylation statuses were examined with an Infinium HumanMethylation450K BeadChip and sodium bisulfite sequencing. DNA methylation at the T-DMRs of ESR1 were significantly higher in OE than in EE, but no significant differences were observed in the DNA methylation statuses of ESR2 and PGR. CONCLUSIONS: Aberrant DNA methylation of the T-DMR was associated with the impaired expression of ESR1, but not the altered expressions of ESR2 and PGR, in OE. FAU - Maekawa, Ryo AU - Maekawa R AUID- ORCID: 0000-0003-0923-376X AD - Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube, 755-8505, Japan. rmaekawa@yamaguchi-u.ac.jp. FAU - Mihara, Yumiko AU - Mihara Y AD - Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube, 755-8505, Japan. FAU - Sato, Shun AU - Sato S AD - Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube, 755-8505, Japan. FAU - Okada, Maki AU - Okada M AD - Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube, 755-8505, Japan. FAU - Tamura, Isao AU - Tamura I AD - Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube, 755-8505, Japan. FAU - Shinagawa, Masahiro AU - Shinagawa M AD - Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube, 755-8505, Japan. FAU - Shirafuta, Yuichiro AU - Shirafuta Y AD - Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube, 755-8505, Japan. FAU - Takagi, Haruka AU - Takagi H AD - Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube, 755-8505, Japan. FAU - Taketani, Toshiaki AU - Taketani T AD - Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube, 755-8505, Japan. FAU - Tamura, Hiroshi AU - Tamura H AD - Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube, 755-8505, Japan. FAU - Sugino, Norihiro AU - Sugino N AD - Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube, 755-8505, Japan. LA - eng GR - C16K11142/Japan Society for the Promotion of Science/ GR - C16K11091/Japan Society for the Promotion of Science/ GR - C18K09262/Japan Society for the Promotion of Science/ GR - C17K11239/Japan Society for the Promotion of Science/ GR - C18K09230/Japan Society for the Promotion of Science/ GR - 18K16801/Japan Society for the Promotion of Science/ GR - 18K16772/Japan Society for the Promotion of Science/ PT - Journal Article DEP - 20190206 PL - England TA - J Ovarian Res JT - Journal of ovarian research JID - 101474849 RN - 0 (ESR1 protein, human) RN - 0 (ESR2 protein, human) RN - 0 (Estrogen Receptor alpha) RN - 0 (Estrogen Receptor beta) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Progesterone) SB - IM MH - Adult MH - DNA Methylation/*genetics MH - Endometriosis/*genetics/metabolism/pathology MH - Endometrium/metabolism/pathology MH - Estrogen Receptor alpha/*genetics/metabolism MH - Estrogen Receptor beta/genetics/metabolism MH - Female MH - Gene Expression Regulation/*genetics MH - Humans MH - Ovarian Diseases/*genetics/metabolism/pathology MH - RNA, Messenger/genetics/metabolism MH - Receptors, Progesterone/genetics/metabolism PMC - PMC6364435 OTO - NOTNLM OT - DNA methylation OT - Endometriosis OT - Estrogen receptor 1 OT - Estrogen receptor 2 OT - Eutopic endometrium OT - Ovarian endometrioma OT - Progesterone receptor OT - Steroid receptor COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: This study was reviewed and approved by the Institutional Review Board of Yamaguchi University Graduate School of Medicine. Written informed consent was obtained from the participants before the collection of any samples, and the specimens were irreversibly de-identified. All experiments involving the handling of human tissues were performed in accordance with Tenets of the Declaration of Helsinki. CONSENT FOR PUBLICATION: Written informed consent for publication was obtained from the participants before the collection of any samples. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2019/02/08 06:00 MHDA- 2019/05/02 06:00 PMCR- 2019/02/06 CRDT- 2019/02/08 06:00 PHST- 2018/11/18 00:00 [received] PHST- 2019/01/28 00:00 [accepted] PHST- 2019/02/08 06:00 [entrez] PHST- 2019/02/08 06:00 [pubmed] PHST- 2019/05/02 06:00 [medline] PHST- 2019/02/06 00:00 [pmc-release] AID - 10.1186/s13048-019-0489-1 [pii] AID - 489 [pii] AID - 10.1186/s13048-019-0489-1 [doi] PST - epublish SO - J Ovarian Res. 2019 Feb 6;12(1):14. doi: 10.1186/s13048-019-0489-1.