Global profiling of proteins in the ventral prostate of older rats subjected to maternal protein restriction associated with postnatal sugar consumption

Abstract

Maternal exposure to low protein diet (LPD) during the intrauterine and postnatal life causes chronic diseases, such as obesity, diabetes and even some types of cancer. This condition is known as Fetal Programming (FP), whose increase has been mainly related to sedentary life style and consumption of high-energy food, provided mostly by saturated fat and carbohydrates and "added sugar". The surge in sugar consumption is primarily related to the intake of sugary foods and beverages. Our research group demonstrated that maternal LPD has been associated with impairment of offspring prostate morphogenesis and increased incidence of prostatic disorders with aging. However, the molecular mechanism involved in these alterations are still poorly understood. Our aim is to analyze the potential changes in global protein expression caused by maternal LPD followed by the consumption of sugar in older offspring. Sprague Dawley pregnant female rats were divided into two groups: Control Group (CTR, n=10) that received control diet (17% protein) during the gestation and lactation periods; and Gestation and Lactation Low Protein Group (GLLP, n=10) fed with low protein diet (6% protein) throughout these periods. After weaning, the male offspring were divided into 4 groups: Control (CTR): rats received filtered water; Control+Sugar (CTR+SU): rats were given 10% sugar solution diluted in filtered water; Gestation and Lactation Low Protein Group (GLLP): rats received filtered water; Gestation and Lactation Low Protein Group +Sugar (GLLP+SU): rats were given 10% sugar solution diluted in filtered water. The sugar solution was offered from weaning to postnatal day (PND) 90. The animals were euthanized on PND540, the ventral prostate (VP) were collected and stored in liquid nitrogen for mass spectrometry analysis at the University of Toronto, Canada in collaboration with Dr. Thomas Kislinger. During the 6 months internship, we will compare our data to the human prostatic adenocarcinoma data available in the "The Cancer Genome Atlas" database (TCGA), in order to find potential molecular pathways deregulated in the VP of LPD offspring that could be related to the development of prostatic lesions in older animals. Thus, we expect to improve the knowledge if the prostate aging process is affected by maternal LPD and/or sugar consummed, but also identify common potential signaling pathways between the aging of rat and process of human prostate carcinogenesis. The internship at Dr. Kislinger's Lab will provide the PhD Candidate Ketlin Colombelli experience in proteomics and bioinformatics analysis. These skills will be useful for the advancement of her PhD research when she returns to Brazil. (AU)