Sex-specific differences in the effects of maternal protein restriction on offspring in early developmental biology: systemic and pituitary consequences

• Grant number: 24/04347-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2024
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Luis Antonio Justulin Junior
• Grantee: Gustavo Monezzi Cordeiro
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Maternal malnutrition is a worldwide problem, and this condition encompasses both exacerbated diets and malnutrition and restriction of certain macromolecules. The consequences of these adversities are linked to the concept of the Developmental Origins of Health and Disease (DOHaD), an area of knowledge that postulates that effects on the gestational and/or lactational environment can influence the most diverse organs and systems in offspring throughout biology of development. One of the experimental models used to investigate the association of health and disease with maternal exposure is Maternal Protein Restriction (MPR), which leads to increased maternal glucocorticoids, delayed development in early life, decreased serum levels of insulin, albumin and testosterone, hypertension throughout life and incidence of prostate cancer with aging. MPR can also affect the pituitary gland, a gland in the endocrine system responsible for the secretion and production of several hormones, having a series of functions on reproductive homeostasis, growth and catabolic and anabolic processes. However, studies on the different sex-specific consequences of MPR on the pituitary glands in early life have not yet been investigated. Therefore, the objective of this project is to evaluate whether RPM affects the morphophysiology of the pituitary gland of male and female post-weaning rats, contrasting with the metabolic impacts. For this, Sprague Dawley rats will be used, divided into 2 groups: Male and female rats born to mothers fed a normoprotein diet (CTR, 17% protein) or a hypoprotein diet (GLLP, 6% protein) during pregnancy and lactation. The animals will be euthanized on postnatal day (PND) 21, with blood and pituitary glands (adenohypophysis and neurohypophysis) collected. The pituitary glands will be processed, and morphological parameters (morphometry and electron microscopy) and gene expression (rTqPCR) will be analyzed, and the blood used for hormonal analyzes (ELISA). Thus, the expected results are that there will be negative effects on the morphophysiology of the pituitary glands at the beginning of life, which impacts the cellular response of the different regions of the pituitary gland, as well as gene expression and hormonal levels, with different sex-specific responses, which which can lead to adversities throughout the systemic environment, creating a window of susceptibility to metabolic diseases throughout developmental biology.Keywords: DOHaD, Maternal malnutrition, Pituitary gland, Metabolism.