Morphological and visceral evaluation of fetuses after preconceptional and gestational exposure to Nitrosodimethylamine in rats

• Grant number: 24/06555-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2024
• End date: February 28, 2025
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Arielle Cristina Arena
• Grantee: Júlia Tavares Alves
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

N-nitrosamines are compounds belonging to the class of environmental contaminants and can be found in various products, including food and drinking water sources. Recently, the presence of these substances at high levels has been observed in widely used medicines, which has aroused the attention of regulatory agencies around the world. To date, they are known for their ability to cause mutagenic and carcinogenic effects. In addition, there is evidence of their embryotoxic potential. N-nitrosamines are metabolically activated, resulting in the formation of alkylating substances and reactive oxygen species (ROS), favoring the production of oxidative stress, which increases the risk of their deleterious effects on health. Despite this, there is a lack of studies investigating the possible adverse effects on reproduction and embryo-fetal development, especially at low doses, which are considered acceptable within the limits set by regulatory agencies. Therefore, this study aims to analyze the morphological and visceral consequences of preconception and combined gestational exposure (maternal and paternal) on fetal and embryonic development. Males will be exposed to NDMA (0 and 7.2 ng/kg/day; gavage) from the preconceptional period until mating. Females will be exposed to the same doses in the preconceptional, mating and gestational periods. The animals will be divided into two groups: 1) Control (control males x control females) and 2) Combined NDMA (NDMA males x NDMA females). Males will be euthanized after the mating period and females at DG20. The fetuses will be used for morphological and visceral evaluations. All the data obtained will be statistically analyzed.