Identification of potential molecular pathways involved in prostate carcinogenesis in offspring exposed to maternal malnutrition

• Published in: Aging (Albany, NY.) NY.), 2020-10, Vol.12 (20), p.19954-19978
• Main Authors: Santos, Sérgio Alexandre Alcantara, Camargo, Ana Carolina Lima, Constantino, Flávia Bessi, Colombelli, Ketlin Thassiani, Portela, Luiz Marcos Frediani, Fioretto, Matheus Naia, Vieira, José Cavalcante Souza, Padilha, Pedro Magalhães, de Oliveira, Mateus Betta, Felisbino, Sergio Luis, Carvalho, Robson Francisco, Justulin, Luis Antonio
• Format: Article
• Language: English
• Subjects: Age Factors; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Calreticulin - metabolism; Carcinogenesis - metabolism; Diet, Protein-Restricted; Disease Models, Animal; Female; Humans; Male; Malnutrition - complications; Malnutrition - metabolism; Malnutrition - physiopathology; Mass Spectrometry; Maternal Nutritional Physiological Phenomena; Prostatic Neoplasms - etiology; Prostatic Neoplasms - metabolism; Protein Interaction Maps; Proteome; Proteomics; Rats; Research Paper; Signal Transduction
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.104093

The developmental origins of health and disease concept links adult diseases with early-life exposure to inappropriate environmental conditions. Intrauterine and postnatal malnutrition may lead to an increased incidence of type 2 diabetes, obesity, and cardiovascular diseases. Maternal malnutrition (MM) has also been associated with prostate carcinogenesis. However, the molecular mechanisms associated with this condition remain poorly understood. Using a proteomic analysis, we demonstrated that MM changed the levels of proteins associated with growth factors, estrogen signaling, detoxification, and energy metabolism in the prostate of both young and old rats. These animals also showed increased levels of molecular markers of endoplasmic reticulum function and histones. We further performed an analysis that identified commonly deregulated proteins in the ventral prostate of old rats submitted to MM with a mouse model and patients with prostate cancer. In conclusion, our results demonstrated that estrogenic signaling pathways, endoplasmic reticulum functions, energy metabolism, and molecular sensors of protein folding and Ca2+ homeostasis, besides histone, and RAS-GTPase family appear to be involved in this process. Knowledge of these factors may raise discussions regarding the role of maternal dietary intervention as a public policy for the lifelong prevention of chronic diseases.