Action of endocrine disruptor bisphenol A and high-fat diet on gerbil's prostatic lobes

Abstract

Prostate cancer is the main and most frequent neoplastic disease that affects men and although it represents a common cause of morbidity and mortality, it is preventable and healing. However, the molecular pathology of this disease is complex, as well as highly related to age, hereditary factors and androgen dependent, is also influenced by endogenous sex steroid hormones, environmental factors, diet, immune and inflammatory responses. Recent research has demonstrated that exposure to endocrine disruptors, present in the environment, may cause permanent morphophysiological changes in the prostate. These substances have the potential to cause damage to the endocrine system, because mimic steroids hormones may affect your metabolism and act directly on the organs of the reproductive tract. Among these environmental chemicals is the Bisphenol A (BPA). BPA is a monomer released from plastic polymers widely used today. This substance may change prostatic histophysiology, since mimics estrogen and competes with the receptors for these hormones. Recent studies in rodents have shown that exposure to low concentrations of BPA increases significantly the incidence and severity of prostatic cancer. Furthermore, it is reported that BPA is able to influence the regulation of transcription of genes involved in obesity and may promote increased body weight and adiposity. Another environmental factor potentially associated with carcinogenesis is the high-fat diet. The nutrient intake with high caloric density can result in a metabolic syndrome with symptoms associated with insulin resistance, dyslipidemia, degree of obesity and contribute to the growth of prostatic tumors in rodents. Preliminary results from our group using the rodent gerbil (Meriones unguiculatus) as a model for studies on changes in the prostate gland, indicate that the high-fat diet and BPA alone has the potential to increase the incidence of prostate neoplasias. However, the effects of its association on adults has not been verified and, the results may help to understand carcinogenesis process in this rodent. Thus, the objectives of this study are to evaluate for qualitative and quantitative histopathology methods, if the association between a high-fat diet and the endocrine disruptor BPA potentiates the development of prostatic lesions in adult animals and investigate the possible involvement of androgen and estrogen receptors in carcinogenesis stimulated by Bisphenol A and high-fat diet. Moreover, the objective is to determine the effects of administration of BPA and high fat diet on the enzyme 5-alpha reductase 2 and aromatase, involved in the biosynthesis of steroid hormones. Thus, 24 adult gerbils (100 days) will underwent the following experimental conditions: 1) Control: Which receive the control diet, 2) High-fat diet: Which receive high-fat diet, 3) BPA: Animals that receive control diet + BPA concentration of 50¼g/Kg/day in water drinking, 4) High-fat diet + BPA: Animals subjected to high-fat diet + BPA concentration of 50¼g/Kg/day in drinking water. Animals will be killed 6 months after the beginning of the experiment. The ventral and dorsolateral prostatic lobes will be removed, weighed and processed for light microscopy. The methods used will involve quantitative and statistics analysis of the feed intake, intake BPA, body and prostate weight, hormonal measurements, incidence and multiplicity of prostatic lesions and morphological analyzes using cytochemical techniques (HE, Picrossirius and Gomori's Reticulin) and immunohistochemical (Androgen Receptor (AR), Estrogen Receptors (ERa and ERb), Proliferating Cell Nuclear Antigen (PCNA), Smooth Muscle a- Actin, detection of basal cell compartment (p63) and detection of the enzymes 5-alpha reductase 2 and Aromatase). The procedures aim to contribute to better understand the mechanisms by which high-fat diet and the endocrine disruptor BPA contribute to the development of prostatic lesions. (AU)