Avaliação da remodelação tecidual prostática em ratos expostos ao bisfenol A e aos fitoestrógenos genisteína e indol-3-carbinol durante o período perinatal

Abstract

Faced with so many chemical substances inserted in plasticizer products and epoxy resins present in our daily lives, Bisphenol A (BPA) stands out, known for its direct action on hormone-dependent tissues, such as the prostate. Some studies have shown that administration of low doses of BPA during early life, when tissues are especially sensitive to endocrine disruptors, affects various aspects of prostate development. On the other hand, some substances present in plants, such as Indole-3-Carbinol (I3C) and Genistein (GEN), have chemoprotective action on tumor cells, through activation of pro-apoptotic and antiproliferative signaling pathways. Therefore, the present study aims to analyze the prostatic structural characteristics of prepubertal rats, resulting from perinatal exposure to BPA and phytoestrogens and to quantify the percentage of prostatic collagen and analyzing its distribution in the prostatic stroma. Sprague-Dawley pregnant females were divided into 4 experimental groups: C: Control; B: BPA (10 µg/Kg); B+G: BPA (10 µg/Kg) + GEN (5 mg/Kg); B+I: BPA (10 µg/Kg) + I3C (20 mg/Kg). The treatments were performed on the mothers, by gavage, from gestational day 17 to postnatal day (PND) 21. The animals received phytoestrogen-free basal chow and filtered water ad libitum. After euthanasia in DPN22, the animals' prostatic complex was collected, dissected and processed. For this, fractal analysis was performed on slides submitted to hematoxylin-eosin staining, as well as the analysis of epithelial height and stereology. Picrosirius staining was also performed to quantify stromal collagen and fractal analysis. In the BPA group, there was a reduction in the stromal compartment when compared to the control group. This reduction was reversed in the groups that underwent GEN or I3C administration. The groups treated with BPA and phytoestrogens showed a reduction in epithelial height when compared to the C group. Such changes found in the stereo-morphometric analyzes were not evidenced by the fractal analysis. There was an increase in the area occupied by collagen in the groups submitted to administration of BPA and phytoestrogens in relation to the control group. Regarding the distribution pattern of these fibers, fractal analysis revealed higher values in all treated groups. Thus, it was found that BPA mainly altered the prostatic stroma, with less influence of phytoestrogens in the reversal of these parameters, which can affect glandular development and cause repercussions in adult life.