Exposição prolongada à uma mistura de desreguladores endócrinos induz lesões pré-neoplásicas na próstata dorsolateral de ratos

Abstract

Endocrine disruptors (ED) are exogenous chemical compounds that can destabilize hormonal action especially in hormone-responsive organs such as the prostate, causing several adverse health effects such as the development of prostatic intraepithelial neoplasia (PIN), accepted as the main precursor lesion of invasive prostatic carcinoma. Most research involving these substances evidences only the evaluation of the effects of EDs alone or in small groups, during short exposure intervals. Therefore, the aim of the present study was to investigate the histological aspects of the dorsolateral prostate of rats exposed during pregnancy, lactation and adulthood to an ED mixture based on environmental exposure. Twenty pregnant females of the Sprague-Dawley strain were divided into 2 experimental groups (control and ED Mix) and exposed during pregnancy and lactation to a mixture consisting of 12 compounds that include phthalates, pesticides, u.v. filters, in addition to bisphenol A and butylparaben (diluted in corn oil by gavage). At 22 days of age, male pups were weaned and continued to receive the full DE mix until 220 days. After euthanasia, the dorsolateral prostate of the animals was collected, dissected and destined for analysis: biometric data, stereological, morphometric, fractal, histological, kariometric, mast cell quantification and collagen identification. The results were analyzed by the T Test (parametric) expressed as mean and standard deviation and Mann-Whitney Test (non-parametric) expressed as median and interquartile range with significance between the groups verified using the Prism 5.0 software (GraphPad), with p value < 0.05). Exposure to the mixture of DE promoted a reduction in the absolute weight of the prostate and epididymis, a decrease in the stromal compartment and an increase in the luminal compartment. The morphometric analysis revealed a decrease in epithelial height in the ED Mix group. The alterations observed in the stereo-morphometric analyzes were not evidenced by the fractal analysis. The administration of toxicants caused the appearance of inflammatory cells, dysplasia and in 80% of the animals the development of PIN. Kariometric analyzes did not reveal significant changes between groups. The number of intact and degranulated mast cells was higher in the animals of the ED Mix group and in relation to collagen identification there was a reduction in both type I and type III collagen. Thus, we conclude that the mixture of DE in an experimental design based on environmental exposure was able to destabilize the histoarchitecture of the dorsolateral prostate, predisposing this microenvironment to the development of pre-neoplastic lesions, inflammation, collagen reduction and morphological changes.