Progesterone Receptor B (PGR-B) Is Partially Methylated in Eutopic Endometrium From Infertile Women With Endometriosis.

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 = 7), with methylation percentage corresponding to 50%, while in the control group the percentage of methylation was 20% (hypomethylated; P = .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.

Perfil diferencial de transcritos em endométrio eutópico de mulheres inférteis com endometriose e controles durante a janela de implantação / Differential profile of transcripts in eutopic endometrium of infertile women with endometriosis during the implantation window

Objetivos: Alterações moleculares no endométrio eutópico de mulheres com endometriose podem estar envolvidas na infertilidade associada à doença. Este estudo objetivou comparar os genes diferencialmente expressos (DEG) no endométrio eutópico de mulheres inférteis com endometriose, controles inférteis (CI; fator masculino e/ou tubário) e controles férteis (CF) durante a janela de implantação, através de RNA­Seq. Material e métodos: Biópsias endometriais foram obtidas de 17 pacientes (seis inférteis com endometriose, seis CI e cinco CF) durante a janela de implantação. O RNA total foi extraído e o RNA­Seq foi feito na plataforma Illumina HISEQ 2500, high output, paired end. A normalização dos dados e a expressão diferencial foram conduzidas no ambiente estatístico R através do pacote DESeq2. Resultados: Os grupos CI e CF foram semelhantes. Nenhum DEG foi identificado quando comparados os grupos CF e endometriose (independentemente do estágio da doença). Cinco DEGs (SCUBE1, CCL20, LGALS9C, TRIM 29 e WNT11) foram identificados no grupo endometriose avançada (EIII/IV) e um DEG (KANSL1­AS1) no grupo endometriose inicial (EI/II), quando comparados com o CF. Dois DEGs (KANSL1­AS1 e VGLL3) foram identificados com a comparação de EI/II e EIII/IV. Conclusões: Os dados sugerem que o endométrio eutópico de mulheres inférteis com endometriose, especialmente na doença avançada, seja molecularmente diferente do endométrio eutópico de mulheres férteis durante a janela de implantação.(AU)

Molecular alterations in the eutopic endometrium of women with endometriosis may be involved in the endometriosis­related infertility. This study aimed to compare the differentially expressed genes (DEG) in eutopic endometrium of infertile women with endometriosis, infertile controls (IC; male and/or tubal factor) and fertile controls (FC) through RNA­Seq. Material and methods: Endometrial biopsies were obtained from 17 patiens (6 infertile women with endometriosis, 6 IC and 5 FC) during the implantation window. The RNA was extracted and the RNA­Seq was performed at a HISEQ 2500 Illumina Platform, high output, paired end. Standardization and differential expression were conducted in the statistical R environment using DESeq2 package. Results: The groups IC and FC were similar. No DEG has been identified comparing CF and endometriosis groups. Five DEGs (SCUBE1, CCL20, LGALS9C, TRIM 29 e WNT11) were identified in the advanced endometriosis (EIII/IV) group, and 1 (KANSL1­AS1) in the initial endometriosis (EI/II) group compared to FC. Two DEGs (KANSL1­AS1 and VGLL3) were identified by comparing EI/II and EIII/IV groups. Conclusions: These data suggest that the eutopic endometrium of infertile women with endometriosis, especially those with advanced disease, may be molecularly different from those of fertile women during the implantation window.(AU)