JBRA Assisted Reproduction 2025;29(Suppl.2 SBRA 2025):75
Poster Presentation
29^th Annual Congress of the SBRA. São Paulo/SP - Brazil, 2025
doi: 10.5935/1518-0557.20263654

P-63. Does lifelong exposure to the pollutant Nitrosodimethylamine compromise reproductive and fertility parameters in male Wistar rats?

Reggina Lorena Mellado Castro¹, Julia Stein¹, Livia Trippe Nagaoka¹, Giovanna Ferrari Rosalem¹, Julia Vitória Francisco De Aquino¹, Julia Tavares Alves¹, Otavio Galassi Vitale¹, Giovanna Kugel Marraschi¹, Luara Magalhães¹, Sara Tawany Caetano Dos Santos¹, Bárbara Campos Jorge¹, Arielle Cristina Arena¹

¹ Universidade Estadual Paulista - UNESP - Botucatu - SP - Brasil

Objective: Daily exposure to potential endocrine disruptors or xenobiotics during critical developmental windows may compromise individuals' reproductive health. According to the World Health Organization (WHO), infertility affects approximately 15% of the global population, and one of the possible causes includes environmental factors. Regulatory agencies worldwide have already classified N-nitrosamines, as Nitrosodimethylamine (NDMA), as a "Cohort of Concern" due to their genotoxic and carcinogenic potential. Therefore, the aim of this study was to evaluate the indirect and direct exposure of F1 male generation Wistar rats to NDMA, at low doses, from the preconception period to adulthood, and its impact on male reproduction and fertility.
Methods: F1 Wistar rats (12/litter/group) were evaluated after direct and indirect (via parental) exposure to NDMA, divided into eight experimental groups: C– (F0 males/females control and control offspring), M– (F0 females exposed to NDMA and control offspring), P– (F0 males exposed to NDMA and control offspring), MP– (F0 females/males exposed to NDMA and control offspring), C+ (F0 males/females control and offspring exposed to NDMA), M+ (F0 females exposed to NDMA and offspring exposed to NDMA), P+ (F0 males exposed to NDMA and offspring exposed to NDMA), and MP+ (F0 females/males exposed to NDMA and offspring exposed to NDMA). Indirect exposure occurred via parental exposure from postnatal day (PND) 60 to lactational day 22. For direct exposure, one rat per litter received control and one rat per litter was exposed to NDMA from PND 22 to 70. Both exposures were by gavage, receiving 1 mL/kg distilled water as control or 7.2 ng/kg/day of NDMA (CEUA 4704260423). The F1 generation was assessed for sperm morphology and motility, testis oxidative stress through the antioxidant enzymatic activity of catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) and lipid peroxidation marker malondialdehyde (MDA), the histological analysis (staging of seminiferous tubules and Leydig cell nuclei count), as well as through a fertility test, in which male offspring were mated with untreated external females. Experimental groups were compared to the C– group, and results were considered significant at p<0.05.
Results: Regarding sperm parameters, both morphology and motility showed no statistically significant differences, as well as fertility assessment. In the oxidative stress evaluation, GSH and SOD were reduced in the MP+ group compared to the C-, and MDA levels were elevated in the MP– group. In the histological evaluation of staging of seminiferous tubules, there was a reduction in the percentage of stages I–VI in the MP–, C+, and MP+ groups, and an increase in stages VII–VIII in the C+ group; however, no significant differences were found in Leydig cell count between groups.
Conclusion: In conclusion, low-dose NDMA exposure, whether direct or indirect, during critical developmental windows did not significantly impair sperm morphology, motility, or fertility in F1 Wistar males. However, oxidative stress biomarkers and histological alterations in staging of seminiferous tubules were detected. Oxidative imbalance already had evidence that can compromise the spermatic function and this can possibly be associated with alterations in the histology of the testis. These findings suggest that alterations found were not able to compromise reproductive performance in the evaluated parameters, however, further studies are needed to better elucidate these observations.