Impact of maternal protein restriction on the morphophysiology and proteomic profile of the liver of young and senile rats

Abstract

Adverse gestational conditions can lead to irreversible offspring morphofunctional changes, a condition established as the Developmental Origin of Health and Disease (DOHaD). Perinatal protein malnutrition (PPM), a model used for studies on DOHaD, has been associated with an increased incidence of cardiovascular and renal diseases, in addition to affecting reproductive parameters and the development of some types of cancer. In this context, it has been shown that the liver, a central organ in the control of metabolism and detoxification, is also affected by exposure to PPM. Our research group demonstrated that PPM impacts the offspring's metabolic parameters, in addition to increasing the incidence of prostatic lesions in aging animals. Thus, this project aims to identify the global profile of protein expression in the liver of rats submitted to PPM (gestational and lactational). For this, the rats were divided into the following experimental groups: 1- Control (CTR): Rats born to dams who consumed a normal diet (17% protein) and water ad libitum during pregnancy and lactation; 2- Perinatal protein malnutrition (PPM): Rats born to dams who consumed low-protein diet (6% protein) during pregnancy and lactation and who later consumed normal diet and water ad libitum until postnatal day (PND) 90 and 540. In PND 90 and 540 the animals were anesthetized, weighed, euthanized and the liver was collected. These samples will be submitted to proteomic analysis by mass spectrometry (LC-Ms/Ms), and morphological and morphometric analyzes and oxidative stress analysis will also be performed. After that, integrative and comparative analyzes of these data between the experimental groups will be performed, in addition to in silico analyses, comparing our results with other experimental models and with patient data. Some targets will be selected for validation by western blotting, immunohistochemistry, or RTqPCR. Thus, it is expected to obtain a global view of the effects of PPM on the offspring's liver.(AU)