Impact of gestational and lactational protein restriction on rat prostate: relationship between the signaling pathway insulin/IGF and glandular development

Abstract

Adverse pregnancy conditions may cause irreversible morphological changes in the fetus, a condition known as Fetal Programming Gestational (PFG). The in utero protein restriction, a model of PFG, results in low birth weight, as well as the increased incidence of development of insulin resistance and Type II diabetes in adult rats. The PFG also changes the levels of steroid hormones and growth factors such as insulin/IGF in the offspring. The insulin/IGF signaling pathway has also been linked to morphogenesis and maintenance of prostatic morphophysiology. Considering recent studies from our group that demonstrated the delayed development of the offspring rat prostate subjected to gestational protein restriction, this project aims to characterize gene and protein expression of the insulin / IGF signaling pathway in normal prostate development, and associating possible changes of this via with delay in glandular development caused by gestational protein restriction/lactation in these periods. For this, Sprague Dawley rats born to mothers fed a normal diet (17% protein, control group) or hypoproteic feed (6% protein) during pregnancy (RPG group), or during pregnancy and lactation (RPGL group) will be used. The ventral prostate lobes (VP) and blood will be collected on postnatal day (PND) 10 and 21. Hormonal dosages of testosterone, estradiol, IGF-1 and insulin will be made in blood of the animals from different experimental groups; analysis of morphological and morphometric parameters of the gland; immunohistochemical analysis for androgen receptor (AR) and Ki67 and real-time PCR for the transcript of insulin, IGF-1 and 2 and its receptor (IGFR1) and western blotting (only for DPN21) will also be made. These data will be related to possible morphological changes in the ventral prostate of animals from restricted groups. This project is part of the research area covered by a regular aid project and a doctoral project, both approved by FAPESP that is in progress (Proc. No. 2013 / 24230-5 and 2014 / 08531-8).