The effects of maternal malnutrition on the pancreas of young male offspring rats: morphological analysis, IGF/Insulin, and tissue oxidative stress pathways

Abstract

The DOHaD (Developmental Origin of Health and Diseases) concept seeks to establish the correlation between the incidence of diseases in adult life and in aging in view of the events suffered during early development. One of his most used models for DOHaD studies is the submission of rodents to maternal protein restriction (MPR). Experimental studies have already shown that it is responsible for low birth weight, smaller size, decreased fat deposits, altered serum levels of steroid hormones and growth factors that are essential for offspring growth, intra tissue oxidative stress in the most diverse organs, in addition to being associated with the development of metabolic syndromes in adult life. Knowing the importance of the pancreas in maintaining an individual's systemic homeostasis, it seems essential to us to investigate the impact of MPR on pancreatic morphophysiology, associating these changes to important pathways for the emergence of pancreatic lesions throughout life, such as IGF/Insulin signaling pathways and oxidative stress. Thus, male offspring of Sprague Dawley rats will be used, which were divided into two experimental groups: the control group (CTR, n=10, rats fed during pregnancy and lactation with a diet with 17% protein) and the gestational protein restriction and lactational (RPGL, n=10, rats fed a diet with 6% protein), at the time of weaning, on a postnatal day (PND) 21 the animals will be anesthetized, blood collected and pancreas dissected, and separated to be fixed for morphological analysis (n=6/animals group), the other pancreas will be frozen for protein extraction to be performed protein expression analysis for Insulin, Insulin Receptor (IR1 and IR2), IGF-1 Receptor, and IGF-binding protein 1 (IGFBP 3), in addition to colorimetric assays for the measurement of SOD, CAT and GSH activity. With this project, we hope to associate the impact of RPM on the morphophysiology of the pancreas of young rats, associating the changes to molecular pathways that may contribute throughout life to pancreatic dysfunction.