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Histopathological repercussions of the endocrine disrupters bisfienol-A and 17-beta-oestradiol on mammary glands and female prostate of the Mongolian Gerbil and their relatioships with the chemically induced carcinogenesis by MNU

Abstract

The development of new treatments against diseases related to the mammary gland and prostate depends on the knowledge about the morphology, physiology and pathology of these glands. Gerbils (Meriones unguiculatus) have been widely used in scientific experiments, since they have an affordable maintenance cost, are small, relatively easy to handle and resistant. This project aims to evaluate the histopathological repercussions of the action of the endocrine disrupters bisfienol-A and 17-beta-estradiol on mammary glands and female prostate of the Mongolian gerbils, as well as their relationships with the carcinogenesis chemically induced by MNU. For the morphological characterization of the breast, the mammary glands and prostates of animals at puberty, adults, gestation, lactation and senile will be used. The glandular tissue will be stained with hematoxylin and eosin, Gomori's reticulin and PAS, and the immunohistochemical reactions for ER-alpha and ER-beta receptors, progesterone receptors and alpha-actin will be stained. In the stage of evaluation of the carcinogenic effect in the cells of the mammary gland and female prostate, mothers will be treated during pregnancy and lactation with different doses of bisphenol A or 17-beta-estradiol. From the females born, one group will be treated at 90 days of age with carcinogen N-nitroso-N-methyl-urea (MNU). Pre-neoplastic and neoplastic cell lesions in the female breast and prostate will be evaluated by staining for hematoxylin and eosin, PAS and immunohistochemical reactions to verify the presence of KI67, PCNA and ER-alpha, ER-beta and progesterone receptors, and inflammatory mediators TNF-alpha and COX-2. This study aims to establish comparative patterns for the evaluation of the effects of endocrine disrupters on the two glands since the novelty of these tests lies in the fact that, in this animal species, the females have prostate and thus, a combined study on the endocrine disruption in the two glands at the same time. In addition, other organs will be evaluated for the presence of metastases. At the time of euthanasia, blood will also be collected for serum estradiol dosage and mammary gland and prostate samples for quantification of proteins by molecular methods. (AU)

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Scientific publications (13)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RUIZ, THALLES F. R.; COLLETA, SIMONE J.; DOS SANTOS, DIEGO D.; CASTRO, NAYARA F. C.; CABRAL, AGATA S.; CALMON, MARILIA F.; RAHAL, PAULA; GIL, CRISTIANE D.; GIROL, ANA PAULA; VILAMAIOR, PATRICIA S. L.; et al. Bisphenol A disruption promotes mammary tumor microenvironment via phenotypic cell polarization and inflammatory response. Cell Biology International, v. 47, n. 6, p. 11-pg., . (20/00160-1, 18/23383-6, 20/01240-9)
RUIZ, THALLES F. R.; GRIGIO, VITOR; FERRATO, LUARA J.; DE SOUZA, LORENA G.; COLLETA, SIMONE J.; AMARO, GUSTAVO M.; GOES, REJANE M.; VILAMAIOR, PATRICIA S. L.; LEONEL, ELLEN C. R.; TABOGA, SEBASTIA O. R.. Impairment of steroidogenesis and follicle development after bisphenol A exposure during pregnancy and lactation in the ovaries of Mongolian gerbils aged females. Molecular and Cellular Endocrinology, v. 566, p. 11-pg., . (21/14140-5, 22/00521-0, 18/23383-6, 20/00160-1, 20/01240-9)
ROCHA RUIZ, THALLES FERNANDO; COLLETA, SIMONE J.; LEONEL, ELLEN C. R.; TABOGA, SEBASTIAO ROBERTO. ammary carcinoma in aged gerbil mothers after endocrine disruption in pregnancy and lactatio. Endocrine-Related Cancer, v. 28, n. 11, p. 715-730, . (20/01240-9, 18/23383-6, 20/00160-1)
RIVAS LEONEL, ELLEN CRISTINA; ROCHA RUIZ, THALLES FERNANDO; BEDOLO, CAROLINA MARQUES; PEGORIN CAMPOS, SILVANA GISELE; TABOGA, SEBASTIAO ROBERTO. Inflammatory repercussions in female steroid responsive glands after perinatal exposure to bisphenol A and 17-beta estradiol. Cell Biology International, v. 45, n. 11, . (18/23383-6, 20/01240-9)
MALDARINE, JULIANA S.; SANCHES, BRUNO D. A.; SANTOS, VITORIA A.; GOES, REJANE M.; VILAMAIOR, PATRICIA S. L.; CARVALHO, HERNANDES F.; TABOGA, SEBASTIAO R.. The complex role of telocytes in female prostate tumorigenesis in a rodent model. Cell Biology International, v. N/A, p. 15-pg., . (18/08945-8, 19/14201-4, 18/23383-6)
SANCHES, BRUNO D. A.; LEONEL, ELLEN C. R.; MALDARINE, JULIANA S.; TAMARINDO, GUILHERME H.; BARQUILHA, CAROLINE N.; FELISBINO, SERGIO L.; GOES, REJANE M.; VILAMAIOR, PATRICIA S. L.; TABOGA, SEBASTIAO R.. Telocytes are associated with tissue remodeling and angiogenesis during the postlactational involution of the mammary gland in gerbils. Cell Biology International, v. 44, n. 12, . (18/23383-6, 18/08945-8)
RUIZ, THALLES FERNANDO ROCHA; TABOGA, SEBASTIAO ROBERTO; LEONEL, ELLEN CRISTINA RIVAS. Molecular mechanisms of mammary gland remodeling: A review of the homeostatic versus bisphenol a disrupted microenvironment. REPRODUCTIVE TOXICOLOGY, v. 105, p. 1-16, . (20/01240-9, 18/23383-6)
ROCHA RUIZ, THALLES FERNANDO; RIVAS LEONEL, ELLEN CRISTINA; COLLETA, SIMONE JACOVACI; BEDOLO, CAROLINA MARQUES; PEGORIN DE CAMPOS, SILVANA GISELE; TABOGA, SEBASTIAO ROBERTO. Gestational and lactational xenoestrogen exposure disrupts morphology and inflammatory aspects in mammary gland of gerbil mothers during involution. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY, v. 89, p. 13-pg., . (20/01240-9, 18/23383-6)
SANCHES, BRUNO D. A.; CARVALHO, HERNANDES F.; MALDARINE, JULIANA S.; BIANCARDI, MANOEL F.; SANTOS, FERNANDA C. A.; VILAMAIOR, PATRICIA S. L.; TABOGA, SEBASTIAO R.. Differences between male and female prostates in terms of physiology, sensitivity to chemicals and pathogenesis-A review in a rodent model. Cell Biology International, . (09/16150-6, 18/23383-6)
SANCHES, BRUNO D. A.; MALDARINE, JULIANA S.; VILAMAIOR, PATRICIA S. L.; FELISBINO, SERGIO L.; CARVALHO, HERNANDES F.; TABOGA, SEBASTIAO R.. Stromal cell interplay in prostate development, physiology, and pathological conditions. PROSTATE, v. 81, n. 13, . (18/08945-8, 18/23383-6)
SANCHES, BRUNO D. A.; CARVALHO, HERNANDES F.; MALDARINE, JULIANA S.; BIANCARDI, MANOEL F.; SANTOS, FERNANDA C. A.; VILAMAIOR, PATRICIA S. L.; TABOGA, SEBASTIAO R.. Differences between male and female prostates in terms of physiology, sensitivity to chemicals and pathogenesis-A review in a rodent model. Cell Biology International, v. 44, n. 1, p. 27-35, . (09/16150-6, 18/23383-6)
ROCHA RUIZ, THALLES FERNANDO; COLLETA, SIMONE JACOVACI; PIRES DE CAMPOS ZUCCARI, DEBORA APARECIDA; LEITE VILAMAIOR, PATRICIA SIMONE; RIVAS LEONEL, ELLEN CRISTINA; TABOGA, SEBASTIAO ROBERTO. Hormone receptor expression in aging mammary tissue and carcinoma from a rodent model after xenoestrogen disruption. Life Sciences, v. 285, . (18/23383-6, 20/01240-9, 20/00160-1)
BEDOLO, CAROLINA MARQUES; RUIZ, THALLES FERNANDO ROCHA; AMARO, GUSTAVO MATHEUS; VILAMAIOR, PATRICIA SIMONE LEITE; LEONEL, ELLEN CRISTINA RIVAS; TABOGA, SEBASTIAO ROBERTO; DE CAMPOS, SILVANA GISELE PEGORIN. The impacts of exposure to bisphenol A in the adult female prostate Meriones unguiculatus. REPRODUCTIVE TOXICOLOGY, v. 119, p. 10-pg., . (21/14140-5, 18/23383-6)

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