Aging of offspring rats submitted to parinatal protein restriction: evaluation of the metabolic status and the insulin / IGF signaling pathway in the ventral prostate at 540 days of age

Abstract

Adverse perinatal conditions (intrauterine and neonatal) may cause irreversible morphological changes in the fetus, a phenomenon known as Fetal Programming (FP). Intrauterine protein restriction, a PF model, is responsible for low birth weight and the development of insulin resistance and type II diabetes in during aging. A maternal protein restriction also changes the levels of steroid hormones and growth factors such as insulin / IGFs in the offspring. The Insulin/ GF signaling pathway has been related to the development as well as prostatic disorders in aging. Thus, this project aims to characterize the metabolic status of offspring rat at 540 days old; the insulin/IGF signaling in the ventral prostate and relate these data to possible incidence of prostatic disorders in these animals. For this, Sprague Dawley rats (CTR group) born to mothers fed a normal diet (17% protein) or hypoproteic feed (6% protein) during pregnancy (RPG Group), or during pregnancy and lactation (RPGL group) will be used. After euthanasia, it will be collected blood and body fat both mothers and offspring. The offspring ventral prostate lobes (PV) will be collected on postnatal day 540. Blood samples, collected from both mothers and offspring of different experimental groups will be used to determine the total protein concentration, glucose, triglycerides: and albumin. The serum levels of insulin, IGF-1 and testosterone will be determined in offspring. Prostate morphological and morphometric parameters will be examined; Immunocytochemical analysis for Ki-67 and androgen receptor (AR); western blotting PCNA, AR PAR4 (apoptosis), AKT and PI3K will be determined and correlated to potential prostatic changes seen in these IGF-1, AKT and PI3K. This project is part of the line of research covered by regular aid project approved by FAPESP (Proc. no. 2013 / 24230-5), and a current PhD project (Proc. no. 2014 / 08531-8).