OBJECTIVE: To define the expression and function of DNA methyltransferases (DNMTs) in response to decidualizing stimuli in endometriotic cells compared with healthy endometrial stroma. DESIGN: Basic science. SETTING: University research center. PATIENT(S): Premenopausal women with or without endometriosis. INTERVENTION(S): Primary cultures of stromal cells from healthy endometrium (E-IUM) or endometriomas (E-OSIS) were subjected to in vitro decidualization (IVD) using 1 μM medroxyprogesterone acetate, 35 nM 17β-estradiol, and 0.05 mM 8-Br-cAMP. MAIN OUTCOME MEASURE(S): Expression of DNMT1, DNMT3A, and DNMT3B in E-IUM and E-OSIS were assessed by quantitative real-time polymerase chain reaction and immunoblotting. Recruitment of DNMT3B to the promoters of steroidogenic factor 1 (SF-1) and estrogen receptor α (ESR1) was examined by chromatin immunoprecipitation. RESULT(S): IVD treatment reduced DNMT3B messenger RNA (74%) and protein levels (81%) only in E-IUM; DNMT1 and DNMT3A were unchanged in both cell types. Significantly more DNMT3B bound to the SF-1 promoter in E-IUM compared with E-OSIS, and IVD treatment reduced binding in E-IUM to levels similar to those in E-OSIS. Enrichment of DNMT3B across 3 ESR1 promoters was reduced in E-IUM after IVD, although the more-distal promoter showed increased DNMT3B enrichment in E-OSIS after IVD. CONCLUSION(S): The inability to downregulate DNMT3B expression in E-OSIS may contribute to an aberrant epigenetic fingerprint that misdirects gene expression in endometriosis and contributes to its altered response to steroid hormones.
OBJECTIVE: To define the expression and function of DNA methyltransferases (DNMTs) in response to decidualizing stimuli in endometriotic cells compared with healthy endometrial stroma. DESIGN: Basic science. SETTING: University research center. PATIENT(S): Premenopausal women with or without endometriosis. INTERVENTION(S): Primary cultures of stromal cells from healthy endometrium (E-IUM) or endometriomas (E-OSIS) were subjected to in vitro decidualization (IVD) using 1 μM medroxyprogesterone acetate, 35 nM 17β-estradiol, and 0.05 mM 8-Br-cAMP. MAIN OUTCOME MEASURE(S): Expression of DNMT1, DNMT3A, and DNMT3B in E-IUM and E-OSIS were assessed by quantitative real-time polymerase chain reaction and immunoblotting. Recruitment of DNMT3B to the promoters of steroidogenic factor 1 (SF-1) and estrogen receptor α (ESR1) was examined by chromatin immunoprecipitation. RESULT(S): IVD treatment reduced DNMT3B messenger RNA (74%) and protein levels (81%) only in E-IUM; DNMT1 and DNMT3A were unchanged in both cell types. Significantly more DNMT3B bound to the SF-1 promoter in E-IUM compared with E-OSIS, and IVD treatment reduced binding in E-IUM to levels similar to those in E-OSIS. Enrichment of DNMT3B across 3 ESR1 promoters was reduced in E-IUM after IVD, although the more-distal promoter showed increased DNMT3B enrichment in E-OSIS after IVD. CONCLUSION(S): The inability to downregulate DNMT3B expression in E-OSIS may contribute to an aberrant epigenetic fingerprint that misdirects gene expression in endometriosis and contributes to its altered response to steroid hormones.
Authors: Petra A B Klemmt; Janet G Carver; Stephen H Kennedy; Philippe R Koninckx; Helen J Mardon Journal: Fertil Steril Date: 2006-03 Impact factor: 7.329
Authors: Kaylon L Bruner-Tran; Juan Gnecco; Tianbing Ding; Dana R Glore; Virginia Pensabene; Kevin G Osteen Journal: Reprod Toxicol Date: 2016-07-14 Impact factor: 3.143
Authors: Lyudmila M Mikhaleva; Victor E Radzinsky; Mekan R Orazov; Tatyana N Khovanskaya; Anastasia V Sorokina; Sergey A Mikhalev; Snezhana V Volkova; Victoria B Shustova; Mikhail Y Sinelnikov Journal: Int J Womens Health Date: 2021-06-01