Study of possible association between endometriosis and phthalate and bisphenol A by biomarkers analysis.

Endocrine disrupting chemicals (EDCs) such as phthalates and bisphenol A (BPA) are substances that may interfere with the actions of endogenous hormones and may be associated with estrogen-related diseases such as endometriosis. This paper describes a case-control study to evaluate the relationship between endometriosis and phthalates and BPA exposure, through biomarkers analysis in urine. The biomarkers of exposure analyzed were metabolites mono-methyl phthalate, mono-isobutyl phthalate (MiBP), mono-butyl phthalate, mono-cyclohexyl phthalate, mono-(ethylhexyl) phthalate, mono-isononyl phthalate, mono-octyl phthalate (MOP), mono-benzyl phthalate and BPA. Urine samples were collected from women aged 18-45 years old. The Study group (n = 30) and Control group (n = 22) were composed of women using as criteria confirmation of endometriosis by videolaparoscopy surgery with histological diagnosis and the absence of the disease, respectively. The analytical method used liquid phase microextraction with determination by gas chromatography coupled to mass spectrometry. The concentrations of biomarkers were adjusted by the creatinine concentration in urine samples of the two groups. The values obtained for the Study Group were compared with the values obtained for the Control Group. The chi-square test and Odds Ratio were used to compare dichotomized phthalate metabolites and BPA metabolite by endometriosis. All nine metabolites were found in different concentrations in the urine samples in both groups The phthalate metabolites that had the highest concentrations, were MOP and MiBP, in which the values of 670 µg g-1 and 560 µg g-1, respectively. The relationship between endometriosis and the all grouped metabolites was evaluated, but was not statistically significant with a 95% CI [X2 (df = 1) = 1.471; p = 0.225]. However, odds ratio (95% confidence interval - CI) for MiBP, which was found at relatively high concentrations in the samples, by endometriosis was 1.929 (0.507-7.332). The food habits and gynecologic history were evaluated and no difference was found between groups. Although no evidences of causal link was found, this study contributes to show that other analysis must be done for evaluating the association between endometriosis and compounds suspected of being EDC.

Iron overload-modulated nuclear factor kappa-B activation in human endometrial stromal cells as a mechanism postulated in endometriosis pathogenesis.

OBJECTIVE: To evaluate the effect of iron overload on nuclear factor kappa-B (NF-κB) activation in human endometrial stromal cells (ESCs). DESIGN: Experimental study. SETTING: University hospital research laboratory. PATIENT(S): Ten healthy women. INTERVENTION(S): Isolated ESCs from endometrial biopsies were incubated with 50 µM FeSO(4) or vehicle. The NF-κB inhibitor [5-(p-fluorophenyl)-2-ureido] thiophene-3-carboxamide (TPCA-1), which inhibits IKKß, the kinase of IκBα (inhibitory protein of NF-κB), was used to prevent iron overload-stimulated NF-κB changes in ESCs. MAIN OUTCOME MEASURE(S): NF-κB activation was assessed by p65:DNA-binding activity immunodetection assay. IκBα, p65, and intercellular adhesion molecule (ICAM)-1 proteins expression was evaluated by Western blots. ESC soluble ICAM (sICAM)-1 secretion was measured by ELISA using conditioned medium. RESULT(S): Iron overload increased p65:DNA-binding activity and decreased IκBα and p65 cytoplasmic expression in ESCs after 30 minutes of incubation as compared with the basal condition. ESC ICAM-1 expression and sICAM-1 secretion were higher after 24 hours of iron overload treatment than in the absence of treatment. TPCA-1 prevented the iron overload-induced increase of p65:DNA binding and IκBα degradation. CONCLUSION(S): Iron overload activates IKKß in ESCs, stimulating the NF-κB pathway and increasing ICAM-1 expression and sICAM-1 secretion. These results suggest that iron overload induces a proendometriotic phenotype on healthy ESCs, which could participate in endometriosis pathogenesis and development.

Análises histoquímica e morfométrica de lesões endometrióticas induzidas em ratas e tratadas com dexametasona / Histochemical and morphometric analysis of endometriotic lesions induced in female rats and treated with dexamethasone

INTRODUÇÃO: A literatura relata que os implantes endometriais possuem receptores para hormônios esteroides, sendo estimulados principalmente pelo estrógeno, e que algumas estratégicas de tratamento têm sido propostas em modelos experimentais, tais como a utilização de glicocorticoides sintéticos, como a dexametasona. OBJETIVO: analisar histoquímica e morfometricamente lesões endometrióticas induzidas em ratas e tratadas com 0,8 mg/kg/dia de dexametasona. MATERIAL E MÉTODOS: Quarenta ratas albinas (linhagem Wistar) com 90 dias de vida, pesando aproximadamente 150 g, foram induzidas à endometriose e divididas em grupos: 1. ratas com endometriose e avaliadas após 34 dias (G1); 2. ratas com endometriose e avaliadas após 47 dias (G2); 3. ratas com endometriose e, após 21 dias do pós-operatório, tratadas com dexametasona por 13 dias (G3) e 4. ratas com endometriose e, após 21 dias do pós-operatório, tratadas com dexametasona por 13 dias e eutanasiadas após um período de 13 dias, contados a partir do término do tratamento com dexametasona (G4). Os fragmentos dos implantes endometriais foram fixados em Bouin, incluídos em paraplast e corados por hematoxilina-eosina e tricrômico de Mallory. As médias do número de glândulas foram submetidas ao teste não-paramétrico de Tukey-Kramer (p < 0,05). RESULTADOS: A dexametasona reduziu a inflamação nos implantes endometriais, o teor de colágeno no estroma e significativamente a área ocupada pelas glândulas (G1= 123,25 ± 6,44ª; G2= 113 ± 6,27ª; G3= 81,66 ± 3,05b; e G4= 94 ± 6,24b). CONCLUSÃO: A dexametasona, na dosagem utilizada, reduz os efeitos estrogênicos em implantes endometriais em ratas.

INTRODUCTION: The literature reports that endometrial implants have receptors for steroid hormones primarily stimulated by estrogen and that some treatment strategies have been proposed in experimental models such as the use of synthetic glucocorticoids, for example, dexamethasone. OBJECTIVE: to analyze histochemically and morphometrically endometriotic lesions induced in rats and treated with dexamethasone (0.8 mg/kg/day). MATERIAL AND METHODS: Forty albino female rats (Wistar strain), with 90 days of age, weighing approximately 150 g, were induced with endometriosis and divided into groups: I - rats with endometriosis and evaluated after 34 days, II - rats with endometriosis and evaluated after 47 days, III - rats with endometriosis and 21 days post-surgery treated with dexamethasone for 13 days and IV - rats with endometriosis and 21 days post-surgery treated with dexamethasone for 13 days and euthanized after a period of 13 days starting from the end of treatment. The fragments of endometrial implants were fixed in Bouin, embedded in Paraplast and stained with hematoxylin-eosin and Mallory trichrome. The mean number of glands was compared through nonparametric Tukey-Kramer test (p < 0,05). RESULTS: Dexamethasone reduced inflammation in the endometrial implants, the collagen content in the stroma and decreased significantly the area occupied by glands (GI - 123.25 ± 6.44ª; IGI - 113 ± 6.27ª; GIII - 81.66 ± 3.05b and GIV - 94 ± 6.24b). CONCLUSION: The applied dexamethasone dosage reduces estrogenic effects in endometrial implants in rats.

Modelo experimental de endometriose em ratas - progressão do implante / Experimental model of endometriosis in rats - implant progression

OBJETIVOS: Desenvolvimento de um modelo experimental de endometriose em ratas, de modo que possibilitecaracterizar a progressão temporal da doença.MATERIAIS E MÉTODOS: Foram utilizadas 40 ratas albinas adultas, nas quais a endometriose foi induzida por meioda fixação de dois fragmentos de corno uterino de 5,0 x 4,0 mm na parede abdominal. Os animais foram submetidosà laparoscopia diagnóstica, com o objetivo de verificar a viabilidade e documentar o aspecto endoscópico daslesões, sendo sacrificados 20 deles após quatro semanas após indução (Grupo I, n=40 implantes) e 20 após oitosemanas (Grupo II, n=40 implantes). Os implantes foram medidos em seu maior comprimento e retirados, sendofixados e processados para análise morfológica.RESULTADOS: No Grupo I, a média do maior diâmetro passou para 5,897 mm (p<0,05) e no Grupo II, para 5,812 mm(p<0,05). A laparoscopia mostrou o aspecto cístico da maioria das lesões e a presença de novos vasos sangüíneospartindo da parede abdominal em direção ao implante. A análise microscópica dos implantes demonstrou umaarquitetura semelhante ao endométrio, com epitélio glandular e estroma típicos desse tecido. CONCLUSÕES: A utilização desse modelo, permitiu documentar as características e a progressão dos implantes através da laparoscopia, sendo também verificado seu crescimento e desenvolvimento histopatológico

Modelo experimental de induçäo de endometriose em ratas / Experimental model of endometriosis induction in rats

RETROSPECTIVA: A endometriose é uma doença nao completamente entendida, constituindo uma área da ginecologia na qual há grande atividade científica. Seria importante para facilitar o estudo dessa moléstia a existência de um modelo experimental de fácil obtençao e com baixo custo. OBJETIVOS: Descrever um modelo de endometriose induzida experimentalmente em ratas que permite a posterior avaliaçao macroscópica, microscópica e bioquímica da patologia. MATERIAIS E MÉTODOS: Foram utilizadas 30 ratas Wistar divididas em dois grupos: 18 animais foram submetidos à laparotomia na qual uma porçao do corno uterino esquerdo foi aberto longitudinalmente até atingir-se a cavidade endometrial, sendo o endométrio manipulado e implantado no peritônio; 12 ratas-controle sofreram apenas laparotomia sem manipulaçao do útero. Sessenta dias após o procedimento, as ratas foram re-operadas para avaliaçao macroscópica dos focos de endometriose e coleta de material para análise microscópica e citológica.RESULTADOS: Dentre as ratas que sofreram abertura uterina e sobreviveram, 84 por cento apresentavam focos macroscópicos de endometriose à re-intervençao. Nenhuma rata do grupo controle apresentou a doença.

[In defense of the pill]. / En defensa de la píldora.

PIP: This article reviews the published literature on studies done on side effects of hormonal contraception, and warns against too adverse reports. The author summarizes advantages and disadvantages of oral contraception (OC), and classifies the information as to whether it results from experimental or epidemiological studies. Known effects of OC are congenital abnormalities, lipid and carbohydrate metabolic effects, hypertension, cardiovascular effects, hepatic effects, and carcinogenic effects. Risks from OC are compared to effectiveness of treatment in itself, and as compared to other contraceptive methods and to the risk of pregnancy, especially for certain categories of women. With OC generalizations are not possible and always dangerous; every single case must be carefully evaluated.^ieng