Maternal malnutrition induces inflammatory pathways and oxidative stress in the dorsolateral prostate of male offspring rats

Abstract

Maternal conditions during pregnancy can influence the long-term health of offspring. In particular, maternal malnutrition (MM), such as protein restriction, affects the development of several organs, including the male reproductive system. This study examined how a low-protein maternal diet impacts the structure and function of the dorsolateral prostate (DLP) in aging male rats. Male offspring were divided into two groups: A control group (CTR), whose mothers received a normal protein diet (17%) during pregnancy and lactation, and a low-protein group (GLLP), whose mothers received a low-protein diet (6%) during the same period. At 540 days of age, the offspring were euthanized, and the DLPs were collected for analysis. The GLLP group showed significant structural changes in the DLP, including increased epithelial and reduced stromal compartments. These rats also had lower levels of probasin (a prostate-specific protein), along with a higher number of mast cells, CD68 + macrophages, and IL-10 protein expression, indicating inflammation. Antioxidant balance was disrupted: Glutathione (GSH) levels increased, while catalase (CAT) and superoxide dismutase (SOD) decreased. The expression of SIRT1, a protein linked to aging and oxidative stress control, was reduced. In silico analysis using human prostate cancer data (PRAD-TCGA) revealed that biological pathways related to oxidative stress, immune response, and tissue remodeling were disrupted in both the rat model and human prostate cancer. In summary, maternal protein restriction leads to long-term changes in the dorsolateral prostate of aging male offspring, including inflammation, oxidative stress, and tissue remodeling. The reduced expression of SIRT1 may play a key role in these effects.