Maternal protein restriction compromises hepatic phenotype and antioxidant defense in postweaning male rats, while females exhibit resilience

Author(s):Show less -

Franzolin, Andre Matheus Leandro ; Fioretto, Matheus Naia ; Ribeiro, Isabelle Tenori ; Maciel, Flavia Alessandra ; Barata, Luisa Annibal ; Vitali, Pedro Menchini ; Magosso, Natalia ; Fagundes, Felipe Leonardo ; Emilio-Silva, Maycon Tavares ; Lima, Clelia Akiko Hiruma ; Scarano, Wellerson Rodrigo ; Justulin, Luis Antonio

• Document type: Journal article
• Source: Biochemical and Biophysical Research Communications; v. 766, p. 11-pg., 2025-04-28.

Abstract

The Developmental Origins of Health and Disease (DOHaD) concept postulates that maternal malnutrition can program offspring for dysfunction of multiple systems, including the liver. Maternal Protein Restriction (MPR) is a maternal malnutrition model that dysregulates catabolic hormones early in life, with long-term consequences on offspring such as hypertension and reproductive system cancers. Furthermore, studies evaluating sex-specific differences are scarce, especially considering the consequences of MPR on early life. Here, we investigated the impacts of MPR on hepatic phenotypic and molecular aspects of male and female rats at postnatal day (PND)21. The rats were divided into two groups: CTR, from dams that consumed a normal-protein diet (17 % protein), or GLLP, from dams that consumed a low-protein diet (6 % protein) throughout gestation and lactation. Our results demonstrated that MPR leads to an increase in collagen fibers, glycogen, and peroxiredoxin 1, in addition to a decrease in reticular fibers, mast cells, GSH, and MDA in the liver of male rats. In females, a reduction of reticular fibers and protein expression of hepatic peroxiredoxin 4 was observed. By contrasting these results with in silico analyses, we suggest that the main altered mechanisms in males are associated with oxidative stress, glycogen metabolism, and inflammatory responses. In females, a subtle dysregulation of antioxidant activity within the extracellular matrix was noted. Therefore, this work demonstrates sex-specific hepatic differences in postweaning rats exposed to MPR, highlighting possible maternal modulations that lead males to be more affected, which may generate long-term effects on hepatic and systemic health. (AU)

• FAPESP's process: 17/01063-7 - Integrative global analyzes of the rat ventral prostate submitted to maternal protein restriction and its repercussions with aging
• Grantee: Luis Antonio Justulin Junior
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/03990-0 - Global expression profile of lncRNAs in the ventral prostate of offspring rats submitted to maternal low protein diet: a DOHaD approach
• Grantee: Luis Antonio Justulin Junior
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/11651-1 - Liver Morphophysiology and Maternal Protein Restriction: Consequences on metabolism and cellular stress
• Grantee: André Matheus Leandro Franzolin
• Support Opportunities: Scholarships in Brazil - Scientific Initiation