Evaluation of Toll-Like Receptor 4 and Nuclear Factor Kappa B expression in the prostate of adult rats exposed to sodium saccharin during gestation and lactation

• Grant number: 25/13464-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Sergio Pereira
• Grantee: Ana Carolina Moura Caputi
• Host Institution: Faculdade de Ciências (FC). Universidade Estadual Paulista (UNESP). Campus de Bauru. Bauru , SP, Brazil

Abstract

Sodium saccharin is a non-caloric artificial sweetener widely used in the food industry, especially in diets seeking a healthy alternative to replace sugar. However, the World Health Organization (WHO) has discouraged the consumption of artificial sweeteners. In line with this, studies have observed that sodium saccharin is capable of crossing the maternal-fetal barrier and acting as an endocrine disruptor in the male reproductive system, affecting sex hormones. Substances with such characteristics can have impacts beyond the embryonic and fetal periods, potentially leading to various damages in the individual during adulthood-a concept known as "DOHaD." Meanwhile, the consumption of sweeteners is increasing, and there are still few studies on the effects of sodium saccharin, especially regarding its consumption during gestation and lactation and its potential consequences for the offspring. Endocrine disruptors mainly affect hormone-dependent organs, such as the prostate, a gland essential for reproduction but vulnerable to hormonal variations, making it more susceptible to tissue lesions and carcinogenesis. Among cancers, prostate cancer is one of the most frequent and lethal worldwide and is commonly triggered by chronic inflammation, which can be caused by substances capable of penetrating the body and interacting with its components, such as endocrine disruptors. Given this, the present study aims to evaluate the intergenerational effects in the F1 generation of gestational and lactational exposure to sodium saccharin on the prostate of adult male rats, focusing on the expression of Toll-Like Receptor 4 (TLR4) and Nuclear Factor Kappa B, both involved in inflammatory processes. For this purpose, pregnant Sprague-Dawley rats will be used and divided into two experimental groups: the control group (C), consisting of rats that will consume food and water ad libitum (n=10); and the sodium saccharin group (S), consisting of rats that will consume food and water ad libitum sweetened with 0.3% sodium saccharin (n=10). After the weaning period, the offspring (F1) will receive food and water ad libitum, and at 120 days of age they will be euthanized. The prostates of each male will then be removed, weighed, and histologically processed for morphological, histopathological, immunohistochemical, and statistical analyses.