Estudo in vitro do desenvolvimento pós-natal da próstata de ratos sob influência de glicose

Abstract

Maternal diabetes interferes with hormone signaling and affects the adult rodent prostate structure. However, the effects of the hyperglycemic environment on the prostate of neonates are not well described. In addition to developing under hyperglycemic conditions, pups of diabetic rats may be born moderately hyperglycemic. Since postnatal events are critical for prostate development and maturation, clarifying the impact of increased glucose concentrations in the first few days after birth is essential. We aimed to evaluate in vitro effects of different glucose concentrations on postnatal prostate development. Prostates were removed from newborn rats (day 0) and cultured for 1, 2 and 3 days in DMEM under glucose at 100 mg / dL (Control), 225 mg / dL (moderate glucose) or 450 mg / dL (high glucose) . Samples were processed for histological analysis (H&E and Picrosirius staining); immunohistochemistry for smooth muscle α-actin and PCNA; or homogenized for evaluation of caspase activity, TGF-β concentration by the ELISA method and quantification of p- ERK1/2 and MMP-2 proteins by Western blot. High glucose concentration reduces the number of prostatic buds and induces massive loss of proliferating cells, both epithelial and stromal, compared to control. The natural increase in collagen deposition observed in the control during the first 3 days of development is affected by increased glucose concentrations since treated groups presented drastic reduction on collagen distribution. In addition, the frequency of smooth muscle cells is also reduced by environments of moderate to high glucose concentrations. The activity of caspase is significantly higher in prostates incubated at moderate glucose concentration and there is an expressive increase of TGF-β concentration in the treated groups compared to control. Finally, it was observed that the activation of p-ERK1 / 2 and the content MMP-2 decreased in the treated groups. These data show that rat prostate postnatal development is affected by elevated glucose levels, imparing glandular structure by mitosis reduction; damage to important signaling molecules, who have part on cell proliferation and survival; by increasing cell death and decreasing stromal elements.