Multigenerational Study of Paternal F2 Generation Male Rats: Evaluations of Reproductive Development after Exposure of the F0 Generation to Nitrosodimethylamine

• Grant number: 24/21958-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Arielle Cristina Arena
• Grantee: Giovanna Kugel Marraschi
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Exposure to environmental contaminants can occur at any time of life, including the so-called critical windows of development. Individuals directly exposed (F0) can show adverse effects in adulthood, as can their indirectly exposed offspring (F2), configuring a multigenerational inheritance. Nitrosamines, a class of substances found in food, widely used medicines and drinking water sources, have proven mutagenic, genotoxic and carcinogenic effects at high doses. Nitrosodimethylamine (NDMA), one of the most important and abundant in this class, due to its high levels of contamination, has a daily dose considered acceptable (96 ng/day), as determined by ANVISA and the FDA. This study aims to evaluate the multigenerational effects on the reproductive development of male rats of the F2 generation of the paternal lineage (PF2) after direct exposure of the F0 generation to NDMA at a low dose. Male and female rats of the F0 generation were divided into 2 experimental groups (control and NDMA) and exposed to NDMA (0 and 7.2 ng/kg/day; via gavage) during the preconception, mating and gestational/lactational periods. The animals mated only with members of their own group to generate the F1 generation, where only male rats followed the study (1 male/litter) and, as adults, mated with external females generating the F2 generation of paternal lineage (PF2). The male offspring of this generation will be assessed for initial development and onset of puberty and, after this period, PF2 were killed to collect organs at DPN 70 and 110 for histopathological, sperm and enzyme analysis. All the data obtained will be subjected to appropriate statistical tests and treated according to their distribution.