Gender Dimorphism in Hepatic Oxidative Stress Induced by Protein Malnutrition During Pregnancy and Childhood

Abstract

Clinically, malnourished infants have increased markers of the metabolic syndrome by adolescence. Similarly, experimental rodent models with low birth weight are associated with hypertension, obesity, high cholesterol, insulin resistance and reduced longevity. Females show lower incidences of several metabolic diseases related to oxidative stress and mitochondrial dysfunction than males. Oxidative stress has been implicated in a large number of human diseases; altered homeostasis for ROS is one essential process that fundamentally contributes to mammalian vulnerability to sexrelated diseases. Gender is a profound determinant factor of disease susceptibility and lifespan. Little is known about gender differences in oxidative homeostasis. This review examines the evidence of the metabolic disease process involving the liver and oxidative stress induced by protein malnutrition in pregnant and lactating mothers, manifested in the adult lives of their offspring. Protein malnutrition in pregnant mothers induced changes in the oxidative status of livers of their offspring with marked sexual dimorphism. The content of reactive oxygen species, protein carbonylation and lipid peroxidation in liver cytosol were higher in males compared to females, although the total antioxidant capacity in males is higher than females. The study also highlights the complex nature of the injury of malnutrition in which the oxidation state correlates with the hepatic injury in a cause-and-effect manner, being higher in males than infemales. An understanding of the reasons for this difference may help us to decrease the susceptibility to metabolic diseases of males and to understand the basic phenomenon of ageing, and to search for safe ways to increase the life span of males. Further elucidation of precise mechanisms responsible for the gender-related differences in the hepatic pathophysiology is essential for the potential clinical application of sex hormone modulation therapy