Deoxyribonucleic acid methyltransferases and methyl-CpG-binding domain proteins in human endometrium and endometriosis

Kim J A F van Kaam, Bert Delvoux, Andrea Romano, Thomas D'Hooghe, Gerard A J Dunselman, Patrick G Groothuis
Fertility and sterility · 2011 · doi:10.1016/j.fertnstert.2011.01.031 · PMID:21316665
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DNMT1 and MBD2 expression increased in the secretory phase of the menstrual cycle and upon hormone treatment, but was lower in endometriosis compared to normal endometrium.

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This in vitro study measured DNA methyltransferase (DNMT1, DNMT2, DNMT3B) and methyl-CpG-binding domain protein (MBD1, MBD2, MeCP2) expression in human endometrium across the menstrual cycle and compared eutopic endometrium with ectopic endometriotic lesions in premenopausal women with and without endometriosis. It used real-time quantitative PCR to quantify gene expression and assessed hormone responsiveness by treating proliferative-phase endometrial explant cultures with vehicle, 17β-estradiol (E2), or E2 plus progesterone (E2+P) for 24 hours. DNMT1 and MBD2 were higher in secretory-phase endometrium than in proliferative-phase and menstrual endometrium, and E2+P up-regulated DNMT1 and MBD2; several DNMTs and MBDs were lower in endometriotic lesions than in eutopic endometrium and in disease-free controls. The paper’s limitation is that it is an in vitro/explant expression study, quantifying mRNA levels without directly demonstrating functional consequences of methylation changes. This paper is centrally about endometriosis — it examines DNMT and MBD expression in eutopic and ectopic endometrium and links the findings to the notion of endometriosis as an epigenetic disease.

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Abstract

OBJECTIVE: To determine [1] expression levels of both DNA methyltransferases (DNMTs) and methyl-CpG-binding domain proteins (MBDs) in human endometrium throughout the menstrual cycle and in eutopic and ectopic endometrium of patients with endometriosis and [2] hormone responsiveness of DNMT and MBD expression in explant cultures of proliferative phase endometrium. DESIGN: In vitro study. SETTING: Academic medical center. PATIENT(S): Premenopausal women with and without endometriosis. INTERVENTION(S): Explant cultures of proliferative phase endometrium were treated with vehicle, 17β-E(2), or a combination of E(2) and P (E(2) + P) for 24 hours. MAIN OUTCOME MEASURE(S): Expression levels of DNMT1, DNMT2, and DNMT3B and MBD1, MBD2, and MeCP2 with use of real-time quantitative polymerase chain reaction. RESULT(S): Expression levels of DNMT1 and MBD2 were significantly higher in secretory-phase endometrium compared with proliferative endometrium and menstrual endometrium. In explant cultures, treatment with E(2) + P resulted in significant up-regulation of DNMT1 and MBD2. Expression levels of several DNMTs and MBDs were significantly lower in endometriotic lesions compared with eutopic endometrium of women with endometriosis and disease-free controls. CONCLUSION(S): These findings suggest a role for DNMTs and MBDs in the growth and differentiation of the human endometrium and support the notion that endometriosis may be an epigenetic disease.
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Abstract

Objective: To determine [1] expression levels of both DNA methyltransferases (DNMTs) and methyl-CpG-binding domain proteins (MBDs) in human endometrium throughout the menstrual cycle and in eutopic and ectopic endometrium of patients with endometriosis and [2] hormone responsiveness of DNMT and MBD expression in explant cultures of proliferative phase endometrium. Design: In vitro study. Setting: Academic medical center. Patient(s): Premenopausal women with and without endometriosis. Intervention(s): Explant cultures of proliferative phase endometrium were treated with vehicle, 17 beta-E(2), or a combination of E(2) and P (E(2) + P) for 24 hours. Main Outcome Measure(s): Expression levels of DNMT1, DNMT2, and DNMT3B and MBD1, MBD2, and MeCP2 with use of real-time quantitative polymerase chain reaction. Result(s): Expression levels of DNMT1 and MBD2 were significantly higher in secretory-phase endometrium compared with proliferative endometrium and menstrual endometrium. In explant cultures, treatment with E(2) + P resulted in significant up-regulation of DNMT1 and MBD2. Expression levels of several DNMTs and MBDs were significantly lower in endometriotic lesions compared with eutopic endometrium of women with endometriosis and disease-free controls. Conclusion(s): These findings suggest a role for DNMTs and MBDs in the growth and differentiation of the human endometrium and support the notion that endometriosis may be an epigenetic disease. (Fertil Steril (R) 2011;95:1421-7.) | Original language | English | |---|---| | Pages (from-to) | 1421-1427 | | Number of pages | 7 | | Journal | Fertility and Sterility | | Volume | 95 | | Issue number | 4 | | DOIs | | | Publication status | Published - Mar 2011 |

Keywords

- Endometriosis - endometrium - DNA methylation - epigenetics - DNMT - MBD Fingerprint Dive into the research topics of 'Deoxyribonucleic acid methyltransferases and methyl-CpG-binding domain proteins in human endometrium and endometriosis'. Together they form a unique fingerprint.Cite this - APA - Author - BIBTEX - Harvard - Standard - RIS - Vancouver

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Condition tags

endometriosis

MeSH descriptors

DNA-Binding Proteins DNA (Cytosine-5-)-Methyltransferases Endometriosis Endometrium Transcription Factors DNA-Binding Proteins DNA-Binding Proteins DNA (Cytosine-5-)-Methyltransferase 1 DNA (Cytosine-5-)-Methyltransferases DNA (Cytosine-5-)-Methyltransferases Endometriosis Endometriosis Endometriosis Endometrium Endometrium Endometrium Female Humans Protein Structure, Tertiary Protein Structure, Tertiary

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