Longa exposição a uma mistura de desreguladores endócrinos predispõe a próstata ventral de ratos à lesões pré-neoplásicas

Abstract

Endocrine disruptors (EDs) are compounds that modify hormone biosynthesis, causing consequences for human health, including chronic diseases such as cancer. The prostate, a hormone-dependent organ, is influenced by EDs both in differentiation processes and in the control of homeostasis in adulthood. Studies have focused only on evaluating the effects of EDs in isolation or in small groups and over short time intervals, not adequately portraying human exposure. Given this, the purpose of the present study is to characterize the effects of exposure to a mixture of EDs based on human exposure from intrauterine life through adulthood on prostate morphology and its histopathological aspects. Pregnant Sprague-Dawley females were randomly assigned to 2 experimental groups: Ctrl Group (vehicle: corn oil, by gavage) and ED Mix Group: received 32.11mg/kg/day of the mixture consisting of twelve compounds (phthalates, pesticides, u.v. filters, bisphenol A, butylparaben) diluted in corn oil (2ml/kg), by gavage. Pregnant or nursing rats received the treatment from gestational day 7 (GD7) to postnatal day 21 (PND21). After weaning, at PND22, male pups of the F1 generation continued to receive the complete ED mixture until 220 days of age, when they were euthanized. The ventral prostate was collected, dissected and processed for histological analysis. Sections stained with hematoxylin-eosin, picrosirius, and toluidine blue were subjected to fractal analysis, stereological, morphometric, karyometric analyses, quantification of relative volume and collagen types, and mast cell counts. ED mixing caused a decrease in epithelial compartment, an increase in fractal dimension, and a decrease in glandular dilatation. In addition, a total decrease in collagen was observed, characterized by both type I and type III collagen. Both groups showed stromal inflammatory foci, but without statistical difference, which reflected in the similar amount of mast cells. There was presence of proliferative lesions, prostatic intraepithelial neoplasia, presence of invasive adenocarcinoma and regions of epithelial atrophy in the group exposed to the ED mixture. It is concluded that the ED mixture was able to cause changes in prostatic histoarchitecture and induce the appearance of preneoplastic lesions.