RESUMO
The diagnosis of peritoneal endometriosis during laparoscopy may be difficult due to the polymorphic aspects of the lesions. Enhanced imaging using contrast agents has potential to provide a better identification of peritoneal endometriosis. The aim of this systematic review is to provide an overview of the literature on what is known about the intraoperative laparoscopic visual enhancement of peritoneal endometriosis using contrast agents. A systematic review was done of studies about enhanced imaging during laparoscopy for endometriosis using contrast agents. Clinical studies which contained a description of imaging with a contrast agent and also reported visual findings of endometriosis during laparoscopy, were included. Nine suitable studies were identified. Intraoperative visualization of endometriosis was analyzed with or without histologic confirmation. Four studies evaluated 5-aminolevulinic acid-induced fluorescence (5-ALA), 1 study evaluated indigo carmine, 2 studies evaluated methylene blue (MB), 1 study evaluated indocyanine green (ICG) and 1 study evaluated so-called bloody peritoneal fluid painting. All studies, with a combined total of 171 included patients, showed potential of enhanced visibility of endometriosis using contrast agents. A combined total of 7 complications, all related to the use of 5-ALA, were reported. We conclude that the use of contrast-based enhanced imaging during laparoscopy is promising and that it can provide a better visualization of peritoneal endometriosis. However, based on the limited data no technique of preference can yet be identified.
Assuntos
Ácido Aminolevulínico , Meios de Contraste , Endometriose/diagnóstico por imagem , Azul de Metileno , Doenças Peritoneais/diagnóstico por imagem , Feminino , Humanos , Laparoscopia , Imagem ÓpticaRESUMO
The 3rd International Consensus Workshop on Research Priorities in Endometriosis was held in São Paulo on May 4, 2014, following the 12th World Congress on Endometriosis. The workshop was attended by 60 participants from 19 countries and was divided into 5 main sessions covering pathogenesis/pathophysiology, symptoms, diagnosis/classification/prognosis, disease/symptom management, and research policy. This research priorities consensus statement builds on earlier efforts to develop research directions for endometriosis. Of the 56 research recommendations from the 2011 meeting in Montpellier, a total of 41 remained unchanged, 13 were updated, and 2 were deemed to be completed. Fifty-three new research recommendations were made at the 2014 meeting in Sao Paulo, which in addition to the 13 updated recommendations resulted in a total of 66 new recommendations for research. The research recommendations published herein, as well as those from the 2 previous papers from international consensus workshops, are an attempt to promote high-quality research in endometriosis by identifying and agreeing on key issues that require investigation. New areas included in the 2014 recommendations include infertility, patient stratification, and research in emerging nations, in addition to an increased focus on translational research. A revised and updated set of research priorities that builds on this document will be developed at the 13th World Congress on Endometriosis to be held on May 17-20, 2017, in Vancouver, British Columbia, Canada.
Assuntos
Consenso , Educação , Endometriose , Pesquisa , Feminino , HumanosRESUMO
Previous studies examining reproductive parameters in men with galactosemia have inconsistently demonstrated abnormalities. We hypothesized that men with galactosemia may demonstrate evidence of reproductive dysfunction. Pubertal history, physical examination, hormone levels and semen analyses were examined in 26 males with galactosemia and compared to those in 46 controls. The prevalence of cryptorchidism was higher in men with galactosemia than in the general population [11.6% vs. 1.0% (95%CI: 0.75-1.26; p <0.001)]. Testosterone (461±125 vs. 532± 33 ng%; p=0.04), inhibin B (144±66 vs. 183±52 pg/mL; p=0.002) and sperm concentration (46±36 vs. 112±75×10(6) spermatozoa/mL; p=0.01) were lower and SHBG was higher (40.7±21.5 vs 26.7±14.6; p=0.002) in men with galactosemia compared to controls. Semen volume was below normal in seven out of 12 men with galactosemia. Men with galactosemia have a higher than expected prevalence of cryptorchidism and low semen volumes. The subtle decrease in testosterone and inhibin B levels and sperm count may indicate mild defects in Sertoli and Leydig cell function, but does not point towards severe infertility causing reproductive impairment. Follow-up studies are needed to further determine the clinical consequences of these abnormalities.
Assuntos
Criptorquidismo/fisiopatologia , Galactosemias/fisiopatologia , Reprodução/fisiologia , Adulto , Criptorquidismo/metabolismo , Galactosemias/sangue , Galactosemias/metabolismo , Humanos , Inibinas/metabolismo , Masculino , Pessoa de Meia-Idade , Sêmen/metabolismo , Sêmen/fisiologia , Contagem de Espermatozoides/métodos , Testosterona/metabolismo , Adulto JovemRESUMO
Endometriosis is defined as the presence of endometrial tissue outside the uterus. It affects 10-15% of women during reproductive age and has a big personal and social impact due to chronic pelvic pain, subfertility, loss of work-hours and medical costs. Such conditions are exacerbated by the fact that the correct diagnosis is made as late as 8-11 years after symptom presentation. This is due to the lack of a reliable non-invasive diagnostic test and the fact that the reference diagnostic standard is laparoscopy (invasive, expensive and not without risks). High-molecular weight gadofosveset-trisodium is used as contrast agent in Magnetic Resonance Imaging (MRI). Since it extravasates from hyperpermeable vessels more easily than from mature blood vessels, this contrast agent detects angiogenesis efficiently. Endometriosis has high angiogenic activity. Therefore, we have tested the possibility to detect endometriosis non-invasively using Dynamic Contrast-Enhanced MRI (DCE-MRI) and gadofosveset-trisodium as a contrast agent in a mouse model. Endometriotic lesions were surgically induced in nine mice by autologous transplantation. Three weeks after lesion induction, mice were scanned by DCE-MRI. Dynamic image analysis showed that the rates of uptake (inwash), persistence and outwash of the contrast agent were different between endometriosis and control tissues (large blood vessels and back muscle). Due to the extensive angiogenesis in induced lesions, the contrast agent persisted longer in endometriotic than control tissues, thus enhancing the MRI signal intensity. DCE-MRI was repeated five weeks after lesion induction, and contrast enhancement was similar to that observed three weeks after endometriosis induction. The endothelial-cell marker CD31 and the pericyte marker α-smooth-muscle-actin (mature vessels) were detected with immunohistochemistry and confirmed that endometriotic lesions had significantly higher prevalence of new vessels (CD31 only positive) than the uterus and control tissues. The diagnostic value of gadofosveset-trisodium to detect endometriosis should be tested in human settings.
Assuntos
Meios de Contraste , Endometriose/diagnóstico , Gadolínio , Imageamento por Ressonância Magnética/métodos , Compostos Organometálicos , Animais , Feminino , CamundongosRESUMO
OBJECTIVE: To determine [1] expression levels of both DNA methyltransferases (DNMTs) and methyl-CpG-binding domain proteins (MBDs) in human endometrium throughout the menstrual cycle and in eutopic and ectopic endometrium of patients with endometriosis and [2] hormone responsiveness of DNMT and MBD expression in explant cultures of proliferative phase endometrium. DESIGN: In vitro study. SETTING: Academic medical center. PATIENT(S): Premenopausal women with and without endometriosis. INTERVENTION(S): Explant cultures of proliferative phase endometrium were treated with vehicle, 17ß-E(2), or a combination of E(2) and P (E(2) + P) for 24 hours. MAIN OUTCOME MEASURE(S): Expression levels of DNMT1, DNMT2, and DNMT3B and MBD1, MBD2, and MeCP2 with use of real-time quantitative polymerase chain reaction. RESULT(S): Expression levels of DNMT1 and MBD2 were significantly higher in secretory-phase endometrium compared with proliferative endometrium and menstrual endometrium. In explant cultures, treatment with E(2) + P resulted in significant up-regulation of DNMT1 and MBD2. Expression levels of several DNMTs and MBDs were significantly lower in endometriotic lesions compared with eutopic endometrium of women with endometriosis and disease-free controls. CONCLUSION(S): These findings suggest a role for DNMTs and MBDs in the growth and differentiation of the human endometrium and support the notion that endometriosis may be an epigenetic disease.
Assuntos
DNA (Citosina-5-)-Metiltransferases/biossíntese , Proteínas de Ligação a DNA/biossíntese , Endometriose/metabolismo , Endométrio/metabolismo , Fatores de Transcrição/biossíntese , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/genética , Proteínas de Ligação a DNA/genética , Endometriose/enzimologia , Endometriose/genética , Endométrio/enzimologia , Endométrio/patologia , Feminino , Humanos , Estrutura Terciária de Proteína/genética , Fatores de Transcrição/genética , Regulação para Cima/genéticaRESUMO
BACKGROUND: Clinical guidelines are intended to improve healthcare. However, even if guidelines are excellent, their implementation is not assured. In subfertility care, the European Society of Human Reproduction and Embryology (ESHRE) guidelines have been inventoried, and their methodological quality has been assessed. To improve the impact of the ESHRE guidelines and to improve European subfertility care, it is important to optimise the implementability of guidelines. We therefore investigated the implementation barriers of the ESHRE guideline with the best methodological quality and evaluated the used instrument for usability and feasibility. METHODS: We reviewed the ESHRE guideline for the diagnosis and treatment of endometriosis to assess its implementability. We used an electronic version of the guideline implementability appraisal (eGLIA) instrument. This eGLIA tool consists of 31 questions grouped into 10 dimensions. Seven items address the guideline as a whole, and 24 items assess the individual recommendations in the guideline. The eGLIA instrument identifies factors that influence the implementability of the guideline recommendations. These factors can be divided into facilitators that promote implementation and barriers that oppose implementation. A panel of 10 experts from three European countries appraised all 36 recommendations of the guideline. They discussed discrepancies in a teleconference and completed a questionnaire to evaluate the ease of use and overall utility of the eGLIA instrument. RESULTS: Two of the 36 guideline recommendations were straightforward to implement. Five recommendations were considered simply statements because they contained no actions. The remaining 29 recommendations were implementable with some adjustments. We found facilitators of the guideline implementability in the quality of decidability, presentation and formatting, apparent validity, and novelty or innovation of the recommendations. Vaguely defined actions, lack of facilities, immeasurable outcomes, and inflexibility within the recommendations formed barriers to implementation. The eGLIA instrument was generally useful and easy to use. However, assessment with the eGLIA instrument is very time-consuming. CONCLUSIONS: The ESHRE guideline for the diagnosis and treatment of endometriosis could be improved to facilitate its implementation in daily practice. The eGLIA instrument is a helpful tool for identifying obstacles to implementation of a guideline. However, we recommend a concise version of this instrument.
Assuntos
Endometriose/diagnóstico , Guias de Prática Clínica como Assunto/normas , Endometriose/terapia , Europa (Continente) , Feminino , Humanos , Desenvolvimento de Programas , Sociedades Médicas , Inquéritos e QuestionáriosAssuntos
Endometriose/genética , Polimorfismo de Nucleotídeo Único , Fator de Crescimento Transformador beta1/genética , Doenças Uterinas/genética , Povo Asiático/genética , Estudos de Casos e Controles , Endometriose/etnologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único/fisiologia , Grupos Populacionais/etnologia , Grupos Populacionais/genética , Doenças Uterinas/etnologiaRESUMO
The prevalence of the BLyS -817C>T polymorphic variant among women with either deep infiltrating endometriosis or adenomyosis compared with a group of gynecologic patients without symptomatic endometriosis and a group of healthy women was assessed in this study. Patients with deep infiltrating endometriosis had less often a BLyS -817C/T genotype as compared with the reference group, with an odds ratio of 0.50 (95% confidence interval 0.27-0.93 versus the C/C genotype).
Assuntos
Fator Ativador de Células B/genética , Endometriose/genética , Doenças Peritoneais/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Adulto , Estudos de Casos e Controles , Endometriose/patologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Razão de Chances , Doenças Peritoneais/patologia , Polimorfismo de Nucleotídeo Único/fisiologia , Regiões Promotoras Genéticas/genética , Adulto JovemRESUMO
Three nulliparous women, aged 39, 34 and 26 years, who were treated for fertility problems and who were affected by endometriosis, presented with ureteral obstruction caused by deep infiltrating endometriosis. The first two patients had complete unilateral loss of kidney function at the time of diagnosis. They chose to have fertility treatment first and both became pregnant. The third patient still had 24% renal function in the affected left kidney. She was treated by complete surgical resection of the endometriosis and reimplantation of the ureter. Ureteral obstruction is a rare, but serious, complication of deep infiltrating endometriosis. Timely recognition is important, since delay results in unnoticed loss of renal function. Clinical investigation for endometriosis of the posterior vaginal fornix is recommended for all patients with chronic abdominal pain, severe dysmenorrhoea or deep dyspareunia. On diagnosis of deep infiltrating endometriosis, further examination is necessary to detect possible ureteral obstruction and consequent hydronephrosis, which can be demonstrated by ultrasound. MRI is of value to map the extent of disease, which is usually multi-focal. Surgery to relieve ureteral obstruction and remove all endometriotic lesions is the treatment of choice if the kidney is still functional.
Assuntos
Endometriose/complicações , Rim/fisiologia , Obstrução Ureteral/etiologia , Adulto , Endometriose/cirurgia , Feminino , Fertilidade/fisiologia , Humanos , Obstrução Ureteral/diagnóstico , Obstrução Ureteral/cirurgiaRESUMO
Several assisted reproduction procedures, such as IVF and ICSI, are available for a variety of infertility problems. In fertility clinics, patients are screened for blood-borne viral infections, including hepatitis B virus (HBV). Reasons for screening are prevention of vertical transmission and laboratory safety. We present the case of a 26-year-old female patient with a chronic HBV infection, whose husband tested negative for hepatitis B. She and her husband were referred to our fertility clinic because of subfertility. Analysis of the husband's semen indicated the necessity of an ICSI procedure. The current Dutch guidelines advise against ICSI in chronic HBV carriers, since the risks and effects of chromosomal integration of HBV DNA in the fetus are not well-known. In this article, we review the scientific evidence for the risk of introducing HBV virus into the oocyte and subsequent integration of HBV DNA into the human genome, and debate the question of whether to do, or not to do, IVF and ICSI.
Assuntos
Fertilização in vitro/ética , Hepatite B Crônica/transmissão , Transmissão Vertical de Doenças Infecciosas , Injeções de Esperma Intracitoplásmicas/ética , Adulto , DNA Viral/sangue , Feminino , Células Germinativas/virologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/complicações , Humanos , Infertilidade/complicações , MasculinoRESUMO
BACKGROUND: Fundamental and genetic differences between women in the endometrium may cause some to develop endometriosis, whereas others do not. Oral contraceptives (OC) may have an effect on the endometrium, rendering the development of endometriosis less likely. STUDY DESIGN: Endometrium from women using OC (OCE) and menstrual endometrium (ME) from normal cycling women were transplanted onto the chicken chorioallantoic membrane (CAM), and endometriosis-like lesion formation was evaluated. Microarray gene expression profiling was performed to identify differentially expressed genes in the endometrium from these groups. Microarray data were validated by real-time PCR. RESULTS: Less endometriosis-like lesions were formed after transplantation of OCE than after transplantation of ME (p<.05). Most of the differentially expressed genes belong to the TGFbeta superfamily. Real-time PCR validation revealed that inhibin betaA (INHBA) expression was significantly decreased in OCE as compared to ME. CONCLUSION: OC use affects the characteristics of endometrium, rendering it less potent to develop into endometriosis.
Assuntos
Anticoncepcionais Orais Hormonais/farmacologia , Endometriose/prevenção & controle , Endométrio/efeitos dos fármacos , Adulto , Animais , Estudos de Casos e Controles , Galinhas , Membrana Corioalantoide , Endométrio/transplante , Feminino , Perfilação da Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Técnicas de Cultura de Tecidos , Adulto JovemRESUMO
It is widely known that angiogenesis plays a key role in endometriotic lesion formation and development. Antiangiogenic treatments aimed at inhibiting new vessel formation have proven efficient in experimental models. However, as antiangiogenic strategies do not target pre-existing pericyte-protected vessels, they require chronic administration and are likely to be beneficial for early-stage disease only or to prevent recurrence after surgery. Moreover, they may have detrimental effects on reproductive function. Vascular-disrupting agents (VDAs) have emerged as a promising new tool for the treatment of tumors. VDAs target established blood vessels, resulting in tumor ischemia and necrosis. These agents may therefore be more efficient against advanced disease. Two major types of VDAs are being developed for cancer: ligand-directed VDAs using antibodies, peptides and growth factors to deliver toxic effectors to tumor endothelium; and small-molecule VDAs exploiting physiological differences between tumor and normal endothelium to induce acute vascular shutdown. The ongoing evolution in genomics and proteomics is revolutionizing the discovery of novel endothelial markers. Several studies suggest that the vasculature of endometriotic lesions may have particular pathophysiological properties, which could be exploited for the development of selective VDAs. The aim of this review is to explore the merits and limitations of vascular therapy for the treatment of endometriosis.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Endometriose/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Inibidores da Angiogênese/efeitos adversos , Animais , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/patologia , Progressão da Doença , Endometriose/patologia , Endométrio/irrigação sanguínea , Endométrio/efeitos dos fármacos , Endométrio/patologia , Feminino , Humanos , Neoplasias/irrigação sanguínea , Neoplasias/tratamento farmacológico , Neovascularização Fisiológica/efeitos dos fármacos , Neovascularização Fisiológica/fisiologiaRESUMO
BACKGROUND: Twin pregnancies after IVF are still frequent and are considered high-risk pregnancies leading to high costs. Transferring one embryo can reduce the twin pregnancy rate. We compared cost-effectiveness of one fresh cycle elective single embryo transfer (eSET) versus one fresh cycle double embryo transfer (DET) in an unselected patient population. METHODS: Patients starting their first IVF cycle were randomized between eSET and DET. Societal costs per couple were determined empirically, from hormonal stimulation up to 42 weeks after embryo transfer. An incremental cost-effectiveness ratio (ICER) was calculated, representing additional costs per successful pregnancy. RESULTS: Successful pregnancy rates were 20.8% for eSET and 39.6% for DET. Societal costs per couple were significantly lower after eSET (7334 euro) compared with DET (10,924 euro). The ICER of DET compared with eSET was 19,096 euro, meaning that each additional successful pregnancy in the DET group will cost 19,096 euro extra. CONCLUSIONS: One cycle eSET was less expensive, but also less effective compared to one cycle DET. It depends on the society's willingness to pay for one extra successful pregnancy, whether one cycle DET is preferred from a cost-effectiveness point of view.
Assuntos
Análise Custo-Benefício , Transferência Embrionária/economia , Fertilização in vitro/efeitos adversos , Gravidez Múltipla , Adulto , Feminino , Custos de Cuidados de Saúde , Humanos , Países Baixos , Gravidez , GêmeosRESUMO
BACKGROUND: Elective single embryo transfer (eSET) in a selected group of patients (i.e. young patients with at least one good quality embryo) reduces the number of multiple pregnancies in an IVF programme. However, the reduced overall multiple pregnancy rate (PR) is still unacceptably high. Therefore, a randomized controlled trial (RCT) was conducted comparing eSET and double embryo transfer (DET) in an unselected group of patients (i.e. irrespective of the woman's age or embryo quality). METHODS: Consenting unselected patients were randomized between eSET (RCT-eSET) (n = 154) or DET (RCT-DET) (n = 154). Randomization was performed just prior to the first embryo transfer, provided that at least two 2PN zygotes were available. Non-participants received our standard transfer policy [SP-eSET in a selected group of patients (n = 100), otherwise SP-DET (n = 122)]. RESULTS: The ongoing PR after RCT-eSET was significantly lower as compared with RCT-DET (21.4 versus 40.3%) and the twin PR was reduced from 21.0% after RCT-DET to 0% after RCT-eSET. The ongoing PRs after SP-eSET and SP-DET did not differ significantly (33.0 versus 30.3%), with an overall twin PR of 12.9%. CONCLUSION: To avoid twin pregnancies resulting from an IVF treatment, eSET should be applied in all patients. The consequence would be a halving of the ongoing PR as compared with applying a DET policy in all patients. The transfer of one embryo in a selected group of good prognosis patients leads to a less drastic reduction in PR but maintains a twin PR of 12.9%.
Assuntos
Transferência Embrionária , Fertilização in vitro , Gravidez Múltipla , Adulto , Feminino , Humanos , Países Baixos , Seleção de Pacientes , Gravidez , Taxa de Gravidez , Gravidez Múltipla/estatística & dados numéricos , GêmeosRESUMO
We have studied menstrual effluent in order to identify soluble menstrual factors that induce epithelial to mesenchymal transitions (EMT) in mesothelial cells. A variety of molecules, such as nitric oxide and its reaction products, proteases (i.e. matrix metalloproteinases, plasmin) and proteins and/or peptides (i.e. growth factors: b-fibroblast growth factor, epidermal growth factor, hepatocyte growth factor, transforming growth factor-beta; cytokines: interleukin 1 beta, tumour necrosis factor-alpha [TNF-alpha]) may be involved in this process. We have demonstrated that TNF-alpha is involved in EMT, whereas the other molecules are not. Biochemical analysis has shown that the inducing menstrual factors are heat-labile molecules, are uncharged at neutral pH, have a molecular weight between 50-70 kDa (or are bound in complexes of that size) and are eluted in the albumin fraction during gel filtration chromatography. Further analysis of this fraction by using proteomics and mass spectrometry has led to the identification of alpha-enolase and haemoglobin whose inhibition partially prevents EMT. When antibodies against TNF-alpha, alpha-enolase and haemoglobin are combined, EMT is almost completely inhibited. Thus, the candidates for soluble menstrual factors that induce mesothelial EMT are TNF-alpha, alpha-enolase and haemoglobin.
Assuntos
Diferenciação Celular/fisiologia , Endométrio/química , Células Epiteliais/química , Menstruação , Mesoderma/citologia , Células Cultivadas , Meios de Cultivo Condicionados/química , Endométrio/citologia , Células Epiteliais/citologia , Feminino , Fibrinolisina/antagonistas & inibidores , Fibrinolisina/metabolismo , Substâncias de Crescimento/metabolismo , Humanos , Interleucina-1/antagonistas & inibidores , Interleucina-1/metabolismo , Espectrometria de Massas , Inibidores de Metaloproteinases de Matriz , Metaloproteinases da Matriz/metabolismo , Mesoderma/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Omento/citologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMO
Tissue integrity of the regurgitated endometrium is pivotal to the development of endometriosis. Occult, submicroscopic lesions occur. Diagnostic laparoscopy may underestimate as well as overestimate the presence of endometriosis.
Assuntos
Endometriose/diagnóstico , Endometriose/etiologia , Endométrio/patologia , Endometriose/classificação , Endometriose/patologia , Feminino , Humanos , Laparoscopia/métodosRESUMO
A prospective study was performed to determine the effects of the angiostatic compounds anti-hVEGF antibody, TNP-470, endostatin, and anginex on the vascularization and on endometriosis-like lesion formation in the chicken chorioallantoic membrane model. Endometriosis-like lesion formation was significantly impaired after treatment with angiostatic agents, which was associated with decreased vessel densities in the surrounding chorioallantoic membrane and more necrosis in the endometriosis-like lesions.
Assuntos
Inibidores da Angiogênese/farmacologia , Membrana Corioalantoide/irrigação sanguínea , Endometriose/prevenção & controle , Neovascularização Patológica/tratamento farmacológico , Sesquiterpenos/farmacologia , Animais , Anticorpos/farmacologia , Embrião de Galinha , Galinhas , Membrana Corioalantoide/patologia , Cicloexanos , Endostatinas/farmacologia , Feminino , Neovascularização Patológica/prevenção & controle , O-(Cloroacetilcarbamoil)fumagilol , Fator A de Crescimento do Endotélio Vascular/imunologiaRESUMO
Peritoneal endometriosis is the result of ectopic implantation and growth of endometrium tissue that has been regurgitated into the abdominal cavity during menstruation. We have previously shown that menstrual effluent induces epithelial to mesenchymal transitions (EMT) in mesothelial cells, which results in cell retraction and exposure of submesothelial extracellular matrix. Since endometrial tissue preferentially adheres to the extracellular matrix, adhesion of endometrial tissue to the peritoneum is facilitated. The EMT were shown to be associated with differential expression and phosphorylation of mesothelial proteins. Using radiolabeling and proteomics we detected changes in protein expression and phosphorylation that occur in mesothelial cells during the EMT process. The identity of 73 proteins, which were obtained from 324 analyzed spots, was confirmed. The expression of 35 proteins involved in organization of the cytoskeleton, signal transduction, regulation of the redox state, and production of ATP, was altered during the EMT process. Four of the identified proteins were differentially phosphorylated: annexin-1, an actin-binding protein and a substrate for receptor tyrosine kinases; tropomyosin-alpha, a regulator of actin filament stability and cell shape; elongation factor 1 delta; ATP synthase beta-chain. In conclusion, factors from menstrual effluent induce specific changes in the expression and phosphorylation status of structural, regulatory and metabolic proteins relevant to the complex process of EMT in mesothelial cells.
Assuntos
Endométrio/fisiologia , Células Epiteliais/metabolismo , Menstruação , Mesoderma/fisiologia , Proteoma/análise , Células Cultivadas , Meios de Cultura/química , Eletroforese em Gel Bidimensional , Endometriose/patologia , Endométrio/citologia , Células Epiteliais/citologia , Feminino , Humanos , Mesoderma/citologia , Radioisótopos de Fósforo , Proteômica/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
BACKGROUND: Matrix metalloproteinases (MMPs) are essential for extracellular matrix remodelling and may contribute to the development of endometriosis. Transplantation of endometrium onto the chicken chorioallantoic membrane (CAM) results in endometriosis-like lesion formation, a process that requires extensive tissue remodelling. We investigated the expression of a wide range of MMPs in menstrual endometrium, endometriosis-like lesions in CAMs, in peritoneal endometriosis and in endometriosis in the rectovaginal space, as well as the function of MMPs in early lesion formation in the CAM model. METHODS: Expression of MMPs was evaluated by immunohistochemistry and MMP function was studied in the CAM by inhibiting MMP activity during lesion formation. RESULTS: Nearly all MMPs were present in all tissues studied. No significant differences in the expression of a majority of MMPs were found in endometriosis-like lesions in CAMs when compared with human endometriosis. Inhibition of MMP-1, -2, -3, -7 and -13 activities significantly impaired endometriosis-like lesion formation in CAMs. CONCLUSIONS: The MMP expression profiles of experimentally induced endometriosis in CAMs and human endometriosis are similar. The prevention of endometriosis-like lesion formation in the CAM by inhibiting MMP activity strongly suggests that MMPs have a function in the early development of endometriotic lesions.