Estrogen- and Progesterone (P4)-Mediated Epigenetic Modifications of Endometrial Stromal Cells (EnSCs) and/or Mesenchymal Stem/Stromal Cells (MSCs) in the Etiopathogenesis of Endometriosis

Endometriosis is a common chronic inflammatory condition in which endometrial tissue appears outside the uterine cavity. Because ectopic endometriosis cells express both estrogen and progesterone (P4) receptors, they grow and undergo cyclic proliferation and breakdown similar to the endometrium. This debilitating gynecological disease affects up to 15% of reproductive aged women. Despite many years of research, the etiopathogenesis of endometrial lesions remains unclear. Retrograde transport of the viable menstrual endometrial cells with retained ability for attachment within the pelvic cavity, proliferation, differentiation and subsequent invasion into the surrounding tissue constitutes the rationale for widely accepted implantation theory. Accordingly, the most abundant cells in the endometrium are endometrial stromal cells (EnSCs). These cells constitute a particular population with clonogenic activity that resembles properties of mesenchymal stem/stromal cells (MSCs). Thus, a significant role of stem cell-based dysfunction in formation of the initial endometrial lesions is suspected. There is increasing evidence that the role of epigenetic mechanisms and processes in endometriosis have been underestimated. The importance of excess estrogen exposure and P4 resistance in epigenetic homeostasis failure in the endometrial/endometriotic tissue are crucial. Epigenetic alterations regarding transcription factors of estrogen and P4 signaling pathways in MSCs are robust in endometriotic tissue. Thus, perspectives for the future may include MSCs and EnSCs as the targets of epigenetic therapies in the prevention and treatment of endometriosis. Here, we reviewed the current known changes in the epigenetic background of EnSCs and MSCs due to estrogen/P4 imbalances in the context of etiopathogenesis of endometriosis

Endometrial lysosomal enzyme activity in ovulatory dysfunctional uterine bleeding, IUCD users and post-partum women

The aim of this study was to evaluate the role of lysosomal enzymes in excessively heavy menstruation by comparing women with menorrhagia due to dysfunctional bleeding or intrauterine contraceptive device (IUCD) use with those with normal menstrual periods or with amenorrhoea associated with breastfeeding. This was a prospective cohort investigation of the activity of four endometrial lysosomal enzymes in three contrasting groups: (i) women with ovulatory dysfunctional uterine bleeding and users of intrauterine contraceptive devices; (ii) breastfeeding post-partum women in whom there are long periods of amenorrhoea, particularly in the early months post-partum; and (iii) normal cycling women. It was found that the total activity of lysosomal enzymes, particularly acid phosphatase and N-acetyl-β-D- glucosaminidase, was markedly elevated (P<0.001) in IUCD-exposed endometrium, and endometrium from women with dysfunctional uterine bleeding when compared with endometrium from women with a history of entirely normal menstrual periods or that in post-partum breastfeeding women. The activity of α-L- fucosidase was moderately elevated in IUCD users (P < 0.05) and ovulatory dysfunctional uterine bleeding (P < 0.05), whereas αD-mannosidase activity was elevated in ovulatory dysfunctional uterine bleeding (P < 0.05), but decreased in IUCD users (P < 0.01). No significant differences were observed in the lysosomal enzyme activities of breastfeeding post-partum women and normal cycling women. These results show that total endometrial tissue activity of four lysosomal enzymes was substantially increased throughout the cycle in most circumstances in women with two different causes for increased menstrual bleeding. This suggests a contributory role to the increased bleeding

Tratamento laparoscópico de 98 pacientes com endometriose intestinal Laparoscopic treatment of 98 women with bowel endometriosis

OBJETIVO: Identificar os tipos de tratamento cirúrgico e a morbidade operatória na endometriose intestinal. MÉTODOS: Estudo retrospectivo de pacientes operadas no Biocor Instituto (Belo Horizonte, MG) por uma equipe multidisciplinar para tratamento de endometriose no período de janeiro de 2002 a junho de 2009. RESULTADO: Noventa e oito pacientes foram submetidas aos seguintes procedimentos para tratamento da endometriose intestinal: ressecção segmentar do reto (n 46; 45,5%), ressecção em disco (n 25; 24,7%), "shaving" (n 18; 17,8%), apendicectomia (n 5; 5%), liberação de aderências sem ressecção (n 5; 5%), ressecção segmentar do sigmóide (n 1; 1%) e ressecção segmentar do colo direito (n 1, 1%). A cirurgia concomitante mais freqüente foi a ressecção de endometriomas ovarianos (n 45). A morbidade operatória foi de 9,2%, sendo as complicações maiores uma fístula retovaginal (1%) e uma deiscência de anastomose (1%). Quarenta e duas pacientes tiveram seguimento médio de 14 meses com recidiva clínica em 8 casos (dor pélvica e dispareunia) e 4 recidivas de imagem à ultrassonografia em parede intestinal, assintomáticas. CONCLUSÃO: O tratamento da endometriose por laparoscopia é factível e seguro, com baixos índices de recidiva.<br>OBJECTIVE: The purpose of this study was to identify the types of surgical procedures performed and the operative morbidity in women with bowel endometriosis. METHODS: Retrospective evaluation of surgical records of women who underwent surgical treatment of endometriosis by a mutidisciplinar team at Biocor Instituto (Belo Horizonte, MG) from January 2002 to June 2009. RESULTS: Ninety-eight women underwent surgical treatment of bowel endometriosis during the study period. The following surgical procedures were performed: segmetnal rectal resection (n 46; 45,5%), intestinal disc excision (n 25; 24,7%), "shaving" (n 18; 17,8%), appendectomy (n 5; 5%), adhesiolysis without intestinal resection (n 5; 5%), segmental sigmoidectomy (n 1; 1%) e segmental right colon resection (n 1, 1%). The most frequent concomitant surgery performed was the removal of ovarian endometriomas (n 45). Operative morbity was observed in 9.2% and major complications were rectovaginal fistula (1%) and anastomosis dehiscence (1%). After a mean followup of 14 months that included 42 patients , recurrence of clinical symptoms (pelvic pain and dyspareunia) was observed in 8 cases as well as 4 cases of asymptomatic intestinal wall endometriosis recurrence which was identified by ultrasonography. CONCLUSION: Laparoscopic treatment of bowel endometriosis is feasible, safe and presents a low recurrence rate