Progesterone's role in deep infiltrating endometriosis: Progesterone receptor and estrogen metabolism enzymes expression and physiological changes in primary endometrial stromal cell culture.

To study progesterone signaling activation, we measured changes in extracellular pH as a reflection of Na+/H+ exchange (NHE) using a cytosensor microphysiometer and assessed progesterone receptor (PR) and estrogen metabolism enzymes mRNA expression in cultured endometrial cells from women with deep infiltrating endometriosis and healthy controls using real-time quantitative PCR. This study was conducted at a University hospital and included patients with and without deep infiltrating endometriosis (DIE). Primary endometrial stromal cells (ECs) from women with DIE and controls were treated with 17ß-estradiol and progesterone prior to microphysiometer measurements and qPCR evaluations. Decreased progesterone responsiveness and decreased total nuclear PR and HSD17B1 mRNA expression were observed in cultured ECs from women with deep infiltrating endometriosis relative to those from control samples before and after hormone treatment. These cells also showed increased 17ß-hydroxysteroid dehydrogenases types 2 (HSD17B2) relative to control group and increased expression of aromatase (CYP19) after exposure to progesterone. These physiological and expression patterns observed in ECs cultures from women with DIE reinforces previous findings in the literature supporting the progesterone resistance hypothesis in the pathogenesis of endometriosis.

Inflammatory cytokine profile of co­cultivated primary cells from the endometrium of women with and without endometriosis.

Endometriosis is a chronic gynecological disorder defined as the presence of endometrial tissue within extra-uterine sites. The primary symptoms are infertility and chronic pain. The inflammatory environment and aberrant immune responses in women with endometriosis may be directly associated with the initiation and progression of endometriotic lesions. In the present study, the secretion of inflammatory cytokines was evaluated in cultures of primary endometrial cells (ECs) isolated from the endometrium of women with and without endometriosis. The presence of endometriotic cells leads to alterations in the secretory profile of healthy ECs. The expression of the inflammatory cytokines interleukin (IL)­6 and IL­8 was significantly increased in endometriotic and co­cultured cells compared with healthy ECs. IL­6 expression was strongly correlated with IL­8 expression in endometriotic cells. IL­1ß expression was increased on day 10 of co­culture to 48.30 pg/ml and may be associated with the long­term co­culture, rather than IL­6 and IL­8 expression. IL­6 expression was strongly correlated with cell number, whereas IL­8 expression was moderately correlated with cell number. Additionally, it was observed that co­cultured cells exhibited a different population of cells, with expression of the mesenchymal stem cell marker cell surface glycoprotein MUC18, indicating a putative role of endometrial mesenchymal stem cells in the secretion of cytokines and disease development. These results indicate a predominant role of primary endometriotic cells in the secretion of cytokines, which contributes to the disrupted peritoneal and endometrial environment observed in the women with endometriosis.

Analysis of Gene Expression in the Endocervical Epithelium of Women With Deep Endometriosis.

Endometriosis affects approximately 12% of reproductive-age women and is currently diagnosed using invasive laparoscopic surgery. Differences in gene expression in the eutopic endometrium between women with and without endometriosis have been reported, and determining the reproducibility of these genetic differences in the endocervical epithelium would represent an important step toward developing novel diagnostic strategies. In this study, we analyzed gene expression in the endocervical epithelium in women with and without moderate or severe endometriosis. Using RT2 Profiler PCR Arrays, we analyzed gene expression in endocervical epithelial cells from women with deep endometriosis (n = 4) and healthy women (n =6). Nine genes were identified as being upregulated: 5 cell cycle genes (cyclin B1 [CCNB1], cyclin G1 [CCNG1], cullin 1 [CUL1], general transcription factor IIH, polypeptide 1 [GTF2H1], and proliferating cell nuclear antigen [PCNA]), 3 cytokine genes (C3, chemokine (C-C motif) ligand 21 [CCL21], and chemokine (C-X-C motif) ligand 14 [CXCL14]) and 1 gene related to dendritic cell pathways (ICAM2), showing that differential gene expression is present in the endocervical epithelium of women with deep endometriosis.

Nutritional aspects related to endometriosis / Aspectos nutricionais relacionados à endometriose

SUMMARY This literature review analyzed the evidence on nutritional aspects related to the pathogenesis and progression of endometriosis. Diets deficient in nutrients result in changes in lipid metabolism, oxidative stress and promote epigenetic abnormalities, that may be involved in the genesis and progression of the disease. Foods rich in omega 3 with anti-inflammatory effects, supplementation with Nacetylcysteine, vitamin D and resveratrol, in addition to the increased consumption of fruits, vegetables (preferably organic) and whole grains exert a protective effect, reducing the risk of development and possible regression of disease. Dietary re-education seems to be a promising tool in the prevention and treatment of endometriosis.

RESUMO Esta revisão de literatura analisou as evidências sobre aspectos nutricionais relacionados com a etiopatogenia e a progressão da endometriose. Dietas deficientes em nutrientes refletem-se em alterações no metabolismo lipídico, estresse oxidativo e favorecem anormalidades epigenéticas que podem estar envolvidas na gênese e na progressão da doença. Alimentos ricos em ômega-3, com efeito anti-inflamatório, suplementação com N-acetilcisteína, vitamina D e resveratrol, além do maior consumo de frutas, verduras (preferencialmente orgânicas) e cereais integrais, exercem efeito protetor, com redução no risco de desenvolvimento e possível regressão da doença. A reeducação alimentar parece ser uma ferramenta promissora na prevenção e no tratamento da endometriose.

Nutritional aspects related to endometriosis.

This literature review analyzed the evidence on nutritional aspects related to the pathogenesis and progression of endometriosis. Diets deficient in nutrients result in changes in lipid metabolism, oxidative stress and promote epigenetic abnormalities, that may be involved in the genesis and progression of the disease. Foods rich in omega 3 with anti-inflammatory effects, supplementation with N-acetylcysteine, vitamin D and resveratrol, in addition to the increased consumption of fruits, vegetables (preferably organic) and whole grains exert a protective effect, reducing the risk of development and possible regression of disease. Dietary re-education seems to be a promising tool in the prevention and treatment of endometriosis.

Indicação da laparoscopia na dor pélvica crônica: revisão baseada em evidências / Indication of laparoscopy in chronic pelvic pain: evidence-based review

Nas últimas décadas, o uso da laparoscopia na ginecologia apresentou aumento expressivo. Ainda é considerada por grande parte dos ginecologistas como a primeira etapa na abordagem das mulheres com dor pélvica crônica. Esta revisão de literatura analisou as indicações da laparoscopia em pacientes com dor pélvica crônica, considerando separadamente os diagnósticos etiológicos mais comuns. Foram utilizadas as bases de dados do Medline-PubMed, Lilacs e Cochrane Library. Esta revisão mostrou que é preciso cautela na indicação do procedimento endoscópico, dado que, em alguns casos, como na endometriose profunda, as complicações são graves e os resultados muitas vezes insatisfatórios, o que justifica maior incentivo ao uso de tratamentos clínicos na abordagem inicial. A laparoscopia deve ser, portanto, empregada como elemento terapêutico em casos criteriosamente selecionados

In the recent decades, the use of laparoscopy in gynecology has had a significant growth. It is still considered by many gynecologists as the first step in the evaluation of women with chronic pelvic pain. This literature review analyzed the indications of laparoscopy in patients with chronic pelvic pain, considering separately the most common etiologies. The databases of Medline, PubMed, Lilacs and Cochrane Library were used. This review showed the need of caution in the indication of endoscopic procedure, because in some cases, as in deep endometriosis, complications are serious and results are often unsatisfactory, which justifies a great incentive to the use of treatment in the initial approach. Laparoscopy should therefore be used as a therapeutic option in carefully selected cases