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

van Kaam, Kim J.A.F.; Delvoux, Bert; Romano, Andrea; D’Hooghe, Thomas; Dunselman, Gerard A.J.; Groothuis, Patrick G.

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

2011

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-E₂, or a combination of E₂ and P (E₂ + 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 E₂ + 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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