Progesterone Receptor B ( PGR-B ) Is Partially Methylated in Eutopic Endometrium From Infertile Women With Endometriosis
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Progesterone Receptor B (PGR-B) Is Partially Methylated in Eutopic Endometrium From Infertile Women With Endometriosis
Reproductive Sciences 1-7 ª The Author(s) 2019 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/1933719119828078 journals.sagepub.com/home/rsx
Carlos Vale´rio Rocha-Junior, MSc1, Michele Gomes Da Broi, PhD1, Cristiana Libardi Miranda-Furtado, PhD1,*, Paula Andrea Navarro, PhD1,2, Rui Alberto Ferriani, PhD1,2, and Juliana Meola, PhD1,2
Abstract Endometriosis is frequently related to infertility and little is known about the mechanisms underlying this association. Some studies point to an endometrial factor involved in this condition, which could compromise embryo implantation. Progesterone plays crucial role in endometrial receptivity by acting through progesterone receptor (PGR) isoforms PR-A and PR-B whose expression is epigenetically regulated by DNA methylation, in a specific promoter region for each isoform. Epigenetic changes in PGR-A and PGR-B may be related to progesterone resistance of endometriosis-related infertility. In order to better understand the mechanisms involved in endometrial receptivity, this case–control study aimed to compare the methylation pattern of PGR-A and PGR-B in eutopic endometrium from infertile women with and without endometriosis during the secretory phase. Endometrial biopsies from 19 patients (10 infertile women with endometriosis and 9 infertile controls) with regular cycles were performed during the secretory phase and were dated according to Noyes’ criteria. The percentage of DNA methylation at PGR-A and PGR-B was carried out by high-resolution melting assay. The PGR-A gene showed 0% of DNA methylation (unmethylated) in both control and endometriosis groups. However, PGR-B gene showed a partially methylated pattern in majority of the patients (n ¼ 7), with methylation percentage corresponding to 50%, while in the control group the percentage of methylation was 20% (hypomethylated; P ¼ .04). The increased percentage of methylation at PGR-B may be related to reduced gene expression, which could compromise the endometrial receptivity in patients with endometriosis. Keywords endometriosis, infertility, endometrial receptivity, progesterone receptor, methylation
Introduction Endometriosis is a benign gynecological disease, characterized by the presence and growth of functional ectopic endometrial tissue,1,2 which affects between 6% and 10% of women of reproductive age.3 Studies suggest a compromised fertility in patients with the disease even in early stages,4-6 considering that 30% to 50% of women with this disorder are infertile.7 However, the mechanisms involved in this condition are not yet fully understood.8 In this regard, evidence indicates that functional endometrium defects may contribute to the decreased fecundity presented by patients with endometriosis.9-14 During the mid-secretory phase, the human endometrium undergoes molecular, histological, and structural changes that allow embryo implantation and the development of a pre
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