Diabetes mellituss is a clinical heterogenic syndrome, caused by the lack of insulin synthesis by the beta cells pancreatic or by target cells-insulin receptor dysfunction. When associated with pregnancy, the diabetes causes maternal/fetal complications, maternal hyperglycemia, fetal overgrowth (macrosomia), all as consequence of higher glucose availability and growth factors on blood flow. The higher birth weight is related to ]the increased risk to develop insulin resistance, obesity and type 2 diabetes in adulthood. The obesity also affects the reproductive system, especially sexual accessory glands and testis. Although many studies had been investigated the effects of the diabetes on testicular functions and fertility, the effects of the gestational diabetes on morphogenesis and growth of the prostate male offspring is limited. Since the prostate is important of male reproduction, here we will investigate the effect of gestational diabetes and the maternal insulin replacement on the male offspring rat ventral prostate, with special attention on senescent related-enzymes, oxidative stress and extracellular matrix-remodeling enzymes. It will be evaluate, in the puberty and in adult-life by immunohistochemistry against Ki67 antigen, and by western blotting and immunohistochemistry the quantification and expression, respectively, of the Glutathione-S-Tranferase (GST-pi), Cicloxigenase-2 (Cox-2), Sirtuin (SIRT-1). It will also be investigate apoptosis and activity of the matrix metalloproteinases (MMPs 2 and 9) by zymography. This project is part of a ongoing regular project (Prof. Fapesp 2012/18100-9).
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