Investigation of the proteomic profile and placental ultrastructure of rats submitted to maternal low protein diet: A DOHaD approach

• Grant number: 24/00809-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2024
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Luis Antonio Justulin Junior
• Grantee: Luisa Annibal Barata
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Epidemiological and experimental studies show that effects on the intrauterine and lactational environment can cause problems in various systems in the offspring. This context is associated with the concept of the Developmental Origins of Health and Disease (DOHaD), and one of its models is Maternal Protein Restriction (MPR), which increases fetal exposure to maternal glucocorticoids, impacts the development of the offspring and increases susceptibility to metabolic diseases and cancer. Thus, the maternal context is essential for understanding the mechanisms affected in the offspring, and research into placental development and homeostasis is noteworthy, as the placenta is a transitional organ responsible for numerous functions crucial to fetal development and growth, one of which is recognizing and responding to environmental changes such as malnutrition and maternal stress, as well as maternal-fetal physiological exchanges and hormone production. The aim of this project is to evaluate the effects of MPR on pregnant rats, with emphasis on the proteomic, morphological and ultrastructural profile of the placenta, and its possible correlation with the impact on the offspring. To this end, rats of the Sprague Dawley strain subjected to MPR will be divided into 2 groups: rats fed a normoprotein diet (CTR, 17% protein) and rats fed a hypoprotein diet (GLP, 6% protein) during gestation. On gestational day (GD) 20, the animals will be euthanized and the placentas will be collected and subjected to morphological and ultrastructural analysis by transmission electron microscopy and proteomic analysis by mass spectrometry and liquid chromatography to evaluate the proteomic profile, in partnership with USP (FOB) in Bauru. After defining this profile, we will identify the pathways and targets differentially expressed in this organ, performing prediction, normalization and enrichment, integrating this data. With these results, we will select targets to be validated using the Western Blotting technique. The expected results refer to the proteins and metabolic pathways deregulated metabolic pathways in mothers subjected to MPR, and can set the context that, already at the beginning of life, multidirectional interactions between the fetus, placenta and mother will define the success of subsequent processes as well as negative consequences in the developmental biology of the offspring, bringing a global panorama of maternal effects and repercussions on the developmental origins of health and disease.