Repercussões do diabetes gestacional no desenvolvimento da próstata de ratos: caracterização histológica, perfil de proliferação e remodelação estromal

Abstract

Gestational diabetes is defined as any degree of reduction of glucose tolerance, whose early detection occurs during pregnancy and may or may not persist after delivery. Studies indicate that the offspring of diabetic mothers display abnormal changes in development as well as metabolic disorders. The prostate gland is androgen-dependent and highly sensitive to hormonal disorders as well as to changes in blood glucose. Recent studies have shown that diabetes causes drastic atrophy in the prostate of rodents, interferes with the proliferation and apoptosis of epithelial cells, alters expression of androgen receptor and leads to significant stromal remodeling. However, little is known about the effects of diabetes later in embryonic development of the prostate. This study was important because there are no studies that show the effects of diabetes on the development of prostate rats whose mothers were diabetic. The aim of this study was to evaluate the organization of epithelial and stromal prostate of adult rats whose embryonic development was under the influence of gestational diabetes. Diabetes was induced in Wistar pregnant females rats by intraperitoneal injection of alloxan (100mg/kg body weight). Male rats offspring of diabetic (PD) and normal mothers (PC) were killed at 12 weeks of age and the ventral prostate was removed, weighed and fixed. The prostate was evaluated for general histology, frequency of collagen fibers, cell death (TUNEL), immunohistochemistry (fibroblasts, fibronectin, smooth muscle cells, cell proliferation - PCNA), western blotting (PCNA, metalloproteinases - MMP-2 and -9, androgen receptors, AKT), zymography and total antioxidant activity and catalase. The prostate of PD animals showed lower weight compared to the PC group and these animals also exhibited hyperglycemia and a significant reduction of testosterone. Cell proliferation as well as the levels of AKT and AR were higher in the offspring of diabetic mothers. The stromal analysis showed that the PD group showed a reduction of -actin, while vimentin and fibronectin did not change. The activity of MMP-2 is increased in PD animals, although the distribution of this MMP was lower in this group. This finding was associated with a significant decrease in collagen distribution. The prostate of the offspring of diabetic rats also showed reduced activity of catalase and total antioxidant activity. The results indicate that rats that developed in a diabetic environment have glycemic and hormonal changes that impact on structural changes in the ventral prostate. Among them, there is greater cell proliferation triggered by AR and AKT and stromal remodeling, which was characterized by increased activity of MMP-2 and collagen degradation. This situation may interfere with tissue architecture and homeostasis glandular. Moreover, the stroma is negatively affected by a decrease in smooth muscle cells, possibly impairing the contraction of the gland as well as the epithelium-stroma interaction stimulated by these cells. This work also shows that gestational diabetes may increase oxidative stress by reducing the activity of enzymes control.