Desenvolvimento e validação de um modelo de endometriose subcutânea em ratas para estudo de prováveis mecanismos fisiopatológicos e do efeito de drogas

In: reponame:Repositório Institucional da Universidade Federal do Ceará (UFC) · 2013 · W2464176850
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A subcutaneous endometriosis model was developed in rats by implanting uterine fragments, showing reproducible endometrioma growth and variable responses to estradiol, medroxyprogesterone acetate, triptorelin pamoate, and acetylsalicylic acid treatments.

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The dissertation studied the development and validation of a subcutaneous endometriosis model in female Wistar rats by implanting 4×4 mm uterine tissue fragments and monitoring endometrioma growth at 1, 7, 14, and 21 days. Endometrial implants were confirmed histologically, and the greatest relative wet and dry weight gain of endometrioma occurred on day 14. The study then assessed the effect of drugs administered on day 5 after implantation, comparing estradiol (dose-dependent increase with the highest dose differing significantly from lower and untreated groups), medroxyprogesterone acetate, triptorelin pamoate, and acetylsalicylic acid using wet and dry relative endometrioma weight as the growth indicator. The main caveat explicitly implied by the design is that growth measurement after short timepoints serves as the primary readout for model validation and drug effect. This paper is centrally about endometriosis — it develops and validates a subcutaneous rat endometriosis model to study mechanisms and drug effects.

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Abstract

Endometriosis is defined as the presence of endometrial tissue (gland and stroma) outside the uterus. The objective of this study was to design a model of subcutaneous endometriosis in rats for the evaluation of the effect of drugs and the pathophysiology of endometriosis. Initially, female Wistar rats (Rattus norvergicus) were implanted subcutaneously with 4x4 mm uterine fragments to evaluate endometrioma growth after 1, 7, 14 and 21 days. Endometrial tissue implants were confirmed by histological analysis. The greatest relative weight gain was observed on the 14th day (wet weight 29.17 ± 6.79 mg%; dry weight 5.36 ± 0.97 mg%). Subsequently, animals were assigned to treatment groups and given either estradiol (2.5 mg/kg, 5 mg/kg, 10 mg/kg sc), medroxyprogesterone acetate (0.5 mg/kg, 2 mg/kg, 5 mg/kg sc), triptorelin pamoate (0.18 mg/kg, 0.56 mg/kg sc) and acetylsalicylic acid (3 mg/kg gavage) on the fifth day following implantation. Wet and dry relative weight of the endometrioma were used as a indicator of growth for model of endometriosis. In the group treated with estradiol, the average wet weight and dry weight on the 14 th day following implantation was 36.62 ± 4.97 mg% and 3.97 ± 1 mg% (2.5 mg), 56.37 ± 20.19 mg% and 9.11 ± 3.85 mg% (5 mg), and 173.89 ± 69.53 mg% and 27.67 ± 10.27 mg% (10 mg), respectively. In the group treated with medroxyprogesterone acetate, the corresponding figures were 13.58 ± 2.53 mg% and 2.67 ± 0.5 mg% (0.5 mg), 14.29 ± 2.07 mg% and 3.71 ± 1.31 mg% (2 mg), and 15.33 ± 7.08 mg% and 2.68 ± 1.44 mg% (5 mg). In the group treated with triptorelin pamoate, the corresponding figures were 20.04 ± 4.02 mg% and 5.21 ± 1.54 mg% (0.18 mg), and 10.86 ± 1.88 mg% and 1.89 ± 0.29 mg% (0.56 mg). In the group treated with 3 mg acetylsalicylic acid, the corresponding figures were 12.81 ± 2.04 mg% and 2.09 ± 0.4 mg%. In the estradiol group, growth gain was dose-dependent: animals receiving 10 mg differed significantly from animals receiving lower doses and from untreated animals (p<0.0001). In conclusion, the model was found to be reproducible and easy to use.
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Please use this identifier to cite or link to this item: http://repositorio.ufc.br/handle/riufc/12693 | Type: | Dissertação | | Title: | Desenvolvimento e validação de um modelo de endometriose subcutânea em ratas para estudo de prováveis mecanismos fisiopatológicos e do efeito de drogas | | Title in English: | Development and a form of endometriose validation subcutaneous under study for possible mechanisms of rats phatophysiological and drug effect | | Authors: | Pereira, Francisco Edson Ximenes Gomes | | Advisor: | Medeiros , Francisco das Chagas | | Keywords: | Endometriose;Modelos Animais;Modelos Animais de Doenças;Endometriosis | | Issue Date: | 2013 | | Citation: | PEREIRA, Francisco Edson Ximenes Gomes. Desenvolvimento e validação de um modelo de endometriose subcutânea em ratas para estudo de prováveis mecanismos fisiopatológicos e do efeito de drogas. 2013. 78 f. Dissertação (Mestrado em Cirurgia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2013. | | Abstract in Brazilian Portuguese: | A endometriose é definida como a presença de tecido endometrial (glândula e estroma) fora do útero (mais precisamente revestimento endometrial). O objetivo foi desenvolver e validar um modelo de endometriose subcutânea em ratas para estudo de prováveis mecanismos fisiopatológicos e do efeito de drogas. Inicialmente, as ratas (Rattus norvergicus, linhagem Wistar) foram implantadas subcutaneamente com fragmentos uterinos 4x4 mm para avaliar o crescimento de endometrioma após 1, 7, 14 e 21dias. Implantes de tecido endometrial foram confirmados por análise histológica. O maior ganho de peso relativo do endometrioma foi observado no dia 14 (peso úmido relativo 29,1 ± 6,79 mg%, peso seco relativo 5,36 ± 0,97 mg%). Posteriormente, os animais foram divididos em grupos e receberam estradiol (2,5 mg/kg, 5 mg/kg, 10 mg/kg sc), acetato de medroxiprogesterona (0,5 mg/kg, 2 mg/kg, 5 mg/kg sc), pamoato de triptorrelina (0,18 mg/kg, 0,56 mg/kg sc) e ácido acetilsalicílico (3 mg/kg gavagem) no quinto dia após a implantação. Peso úmido relativo e seco relativo do endometrioma foram usados como um indicador de crescimento para o modelo de endometriose. No grupo tratado com estradiol, o peso úmido relativo médio e peso seco relativo médio no dia 14 após a implantação foi de 36,62 ± 4,97 mg% e 3,97 ± 1mg % (2,5 mg/kg), 56,37 ± 20,19 mg% e 9,11 ± 3,85 mg% (5 mg/kg), 173,89 ± 69,53 mg% e 27,67 ± 10,27 mg% (10 mg/kg), respectivamente. No grupo tratado com acetato de medroxiprogesterona, os valores correspondentes foram 13,58 ± 2,53 mg% e 2,67 ± 0,5 mg% (0,5 mg/kg), 14,29 ± 2,07 mg% e 3,71 ± 1,31 mg% (2 mg/kg), e 15,33 ± 7,08 mg% e 2,68 ± 1,44 mg% (5 mg/kg). No grupo tratado com pamoato de triptorrelina, os valores correspondentes foram 20,04 ± 4,02 mg% e 5,21 ± 1,54 m% (0,18 mg/kg), e 10,86 ± 1,88 mg% e 1,89 ± 0,29 mg% (0,56 mg/kg). No grupo tratado com ácido acetilsalicílico 3 mg/kg, os valores correspondentes foram 12,81 ± 2,04 mg% e 2,09 ± 0,4 mg%. No grupo de estradiol, o ganho de crescimento foi dependente da dose: os animais que receberam 10 mg/kg diferiram significativamente dos animais que receberam doses mais baixas e a partir de animais não tratados (p < 0,0001). Em conclusão, o modelo mostrou ser reprodutível e fácil de usar. | | Abstract: | Endometriosis is defined as the presence of endometrial tissue (gland and stroma) outside the uterus. The objective of this study was to design a model of subcutaneous endometriosis in rats for the evaluation of the effect of drugs and the pathophysiology of endometriosis. Initially, female Wistar rats (Rattus norvergicus) were implanted subcutaneously with 4x4 mm uterine fragments to evaluate endometrioma growth after 1, 7, 14 and 21 days. Endometrial tissue implants were confirmed by histological analysis. The greatest relative weight gain was observed on the 14th day (wet weight 29.17 ± 6.79 mg%; dry weight 5.36 ± 0.97 mg%). Subsequently, animals were assigned to treatment groups and given either estradiol (2.5 mg/kg, 5 mg/kg, 10 mg/kg sc), medroxyprogesterone acetate (0.5 mg/kg, 2 mg/kg, 5 mg/kg sc), triptorelin pamoate (0.18 mg/kg, 0.56 mg/kg sc) and acetylsalicylic acid (3 mg/kg gavage) on the fifth day following implantation. Wet and dry relative weight of the endometrioma were used as a indicator of growth for model of endometriosis. In the group treated with estradiol, the average wet weight and dry weight on the 14 th day following implantation was 36.62 ± 4.97 mg% and 3.97 ± 1 mg% (2.5 mg), 56.37 ± 20.19 mg% and 9.11 ± 3.85 mg% (5 mg), and 173.89 ± 69.53 mg% and 27.67 ± 10.27 mg% (10 mg), respectively. In the group treated with medroxyprogesterone acetate, the corresponding figures were 13.58 ± 2.53 mg% and 2.67 ± 0.5 mg% (0.5 mg), 14.29 ± 2.07 mg% and 3.71 ± 1.31 mg% (2 mg), and 15.33 ± 7.08 mg% and 2.68 ± 1.44 mg% (5 mg). In the group treated with triptorelin pamoate, the corresponding figures were 20.04 ± 4.02 mg% and 5.21 ± 1.54 mg% (0.18 mg), and 10.86 ± 1.88 mg% and 1.89 ± 0.29 mg% (0.56 mg). In the group treated with 3 mg acetylsalicylic acid, the corresponding figures were 12.81 ± 2.04 mg% and 2.09 ± 0.4 mg%. In the estradiol group, growth gain was dose-dependent: animals receiving 10 mg differed significantly from animals receiving lower doses and from untreated animals (p<0.0001). In conclusion, the model was found to be reproducible and easy to use. | | URI: | http://www.repositorio.ufc.br/handle/riufc/12693 | | Appears in Collections: | DCIR - Dissertações defendidas na UFC | Files in This Item: | File | Description | Size | Format | | |---|---|---|---|---| | 2013_dis_fexgpereira.pdf | 2,35 MB | Adobe PDF | View/Open | Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

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