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)