Toxicological evaluation and reproductive development of male offspring after direct and indirect exposure to Nitrosodimethylamine

• Grant number: 23/17931-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2024
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Morphology - Embryology
• Principal Investigator: Arielle Cristina Arena
• Grantee: Reggina Lorena Mellado Castro
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Infertility is a condition that affects 15% of the world's population and is associated with environmental interferences and lifestyle. Such environmental exposure to harmful substances can occur in both adulthood and critical developmental windows, potentially resulting in infertility or subfertility. These acquired conditions align with the DOHAD (Developmental Origins of Health and Disease) and POHaD (Paternal Origins of Health and Disease) premises, which hypothesize about the maternal and paternal roles in offspring development and health. Among the environmental pollutants that can affect maternal and fetal development, there are N-nitrosamines, produced as unintentional byproducts of manufacturing processes and found in the environment, drinking water, food, and medications. The most abundant nitrosamine in the environment is nitrosodimethylamine (NDMA), which is why it is the target substance of this study. Therefore, this study will assess the potential consequences of paternal, maternal, and combined (paternal and maternal) exposure to Nitrosodimethylamine (NDMA) on toxicological parameters and early sexual parameters in male Wistar rats of the F1 generation. The F0 generation will consist of 40 male and 40 female Wistar rats, paired 1 male: 1 female, and allocated into 4 experimental groups (n=10/group/sex): the control group, maternal NDMA, paternal NDMA, and combined NDMA. The control group will receive 1 mL/kg of distilled water, while the NDMA animals will be exposed to 7.2 ng/kg/day of NDMA (oral route) from postnatal day (PD) 60 to 90, during the mating, gestational, and lactational periods. After birth, the offspring will be evaluated for their initial sexual development and continuously exposed to control (1/sex/litter) and NDMA (1/sex/litter) until PD 70. In adulthood, sexual behavior, fertility tests, organ collection, and hematological parameters will be analyzed.