DNA methylation patterns of steroid receptor genes ESR1, ESR2 and PGR in deep endometriosis compromising the rectum

Autor(es)

Meyer, Joana Ladeira ^[1] ; Zimbardi, Daniela ^[1] ; Podgaec, Sergio ^[2] ; Amorim, Renee Laufer ^[3] ; Abrao, Mauricio Simoes ^[2] ; Rainho, Claudia Aparecida ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Inst Biosci, Dept Genet, BR-18618970 Botucatu, SP - Brazil

^[2] Sao Paulo Univ USP, Dept Obstet & Gynecol, Sao Paulo - Brazil

^[3] Sao Paulo State Univ UNESP, Dept Clin Vet Med, BR-18618970 Botucatu, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Molecular Medicine; v. 33, n. 4, p. 897-904, APR 2014.
• Citações Web of Science: 21

Resumo

Endometriosis is characterized by the presence of endometrial-like tissue located outside the uterine cavity. Recent evidence suggests that endometriosis may be an epigenetic disease, as well as an estrogen-dependent disease. Based on the unique steroid hormone receptor expression profile observed in endometriotic lesions as compared to eutopic endometrium, the present study aimed to gain further insight into the DNA methylation patterns of alternative promoters of the steroid receptor genes ESR1, ESR2 and PGR in intestinal deep endometriosis, one of the most aggressive forms of endometriosis. The DNA methylation patterns were evaluated by methylation-specific polymerase chain reaction (MS-PCR) after bisulfite modification in 44 endometriotic tissues as well as in 7 matched eutopic endometrium. No differences in the DNA methylation were observed for the ESR1 and ESR2 genes. Methylation of the PGR gene was observed in 39% (17 out of 44) and 19% (7 out of 37) of the cases in the promoter regions B (PGRB) and A (PGRA), respectively. Both PGR promoter regions were methylated in 3 cases. PGRB methylated alleles were detected exclusively in the endometriotic lesions when compared to the eutopic endometrium obtained from the same patient. The effect of DNA methylation in inhibiting the PGR gene expression was corroborated by immunostaining for PgR protein in a subset of tissue samples. The present study demonstrated that epigenetic changes occur in both promoter regions of the PGR gene in intestinal endometriosis. Since eutopic and ectopic tissues do not respond sufficiently to progesterone in women with endometriosis, further study is necessary to evaluate the effect of epigenetic alterations in progesterone-resistance in this enigmatic disease. (AU)

• Processo FAPESP: 08/53716-5 - Identificacao de perfis diferenciais de metilacao do dna na endometriose.
• Beneficiário: Claudia Aparecida Rainho
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 08/52270-3 - Identificacao de perfis diferenciais de metilacao do dna na endometriose pela triagem genomica de microarranjos de ilhas cpg.
• Beneficiário: Daniela Zimbardi
• Linha de fomento: Bolsas no Brasil - Mestrado