Exposure of the parental generation to Nitrosodimethylamine (NDMA): multigenerational assessment of toxicological and reproductive parameters of the F0 and F2 generations in male and female rats.

• Grant number: 24/04466-9
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: January 01, 2025
• End date: June 30, 2027
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Arielle Cristina Arena
• Grantee: Lívia Trippe Nagaoka Gonçalves
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated research grant: 22/15364-7 - Implications of parental exposure to nitrosodimethylamine in rats: immediate and multigenerational effects on toxicological and reproductive parameters, AP.R

Abstract

The multigenerational assessment in this study covers the effects of direct exposure on the parental generation (F0) and the possible consequences of this exposure on future generations (F2), even in the absence of direct exposure to the tested substance. N-nitrosamines are substances considered environmental contaminants that appear as unintentional by-products in industrial production. Significant levels of these compounds have been identified in everyday products, drinking water sources, and widely used medicines. Among the identified N-nitrosamines, Nitrosodimethylamine (NDMA) is one of the most abundant in the environment. Recurrent exposure to NDMA may increase the risk of cancer, as well as evidence that it may impact the reproductive health of several species. Although the carcinogenic potential of N-nitrosamines is well established, few studies have investigated their adverse effects on reproduction and, to the best of our knowledge, there are no studies on the effects of NDMA at low doses (considered acceptable by regulatory agencies) and on a multigenerational scale. This study aims to investigate the potential effect of NDMA on the reproductive health of males and females in the F0 generation, as well as their offspring in the F2 generation. In the F0 generation, male and female rats will be exposed to NDMA (0 and 7.2 ng/kg/day; gavage) in the preconception, during mating and gestational/lactational periods. The animals will be divided into four experimental groups (n = 10 animals/group): 1) Control Females; 2) NDMA Females; 3) Male Control; 4) NDMA Males. The animals will be euthanized for hemato-biochemical, sperm, histological, hormonal, gene expression of steroidogenic and antioxidant enzymes evaluations. The offspring of this generation (F1) will be mated to obtain the F2 generation. The animals will be divided into 8 new experimental groups (n = 8 litters/group). The offspring will be evaluated in relation to initial development and onset of puberty. After this period, the animals will be euthanized for organ and blood collection at three different ages: DPN 22, for both, DPN 60 and 70, DPN 100 and 110, for females and males, respectively, for hematological, sperm, histological and hormonal.