BACKGROUND: Mid-gestation is a critical developmental window for organogenesis and neurodevelopment. Maternal exposure to L-aspartyl-L-phenylalanine methyl ester during this period may disrupt embryonic programming through oxidative and inflammatory pathways.
OBJECTIVE: This study aimed to investigate the embryo-toxic, genotoxic, and neurobehavioral impacts of L-aspartyl-L-phenylalanine methyl ester administered at doses of 240 and 300 mg/kg during the mid-gestational stage in pregnant rats.
METHODS: Pregnant Wistar albino rats were divided into three groups: control, 240 mg/kg, and 300 mg/kg of L-aspartyl-L-phenylalanine methyl ester. Assessment included fetal growth parameters, DNA fragmentation (COMET assay), pro-inflammatory cytokines (IL-1β, IL-6), and oxidative stress markers. Additionally, offspring neurobehavioral performance was evaluated using Negative Geotaxis, Swimming Rank, and Cleft Avoidance tests, followed by histopathological examination of fetal brain, liver, and heart tissues.
RESULTS: Mid-gestational exposure triggered a significant dose-dependent oxidative-inflammatory surge. Treated embryos exhibited substantial DNA fragmentation and marked elevations in IL-1β and IL-6 levels. Significant fetal growth restriction was observed alongside distinct sensorimotor and functional impairments in neurobehavioral tests. Histopathological analysis revealed degenerative alterations in the brain, liver, and myocardium, which were more severe at the higher dose (300 mg/kg).
CONCLUSION: The mid-gestational window is exceptionally vulnerable to L-aspartyl-L-phenylalanine methyl ester-induced toxicity. The findings highlight persistent structural and functional disturbances, suggesting the need for stage-specific caution regarding artificial sweetener consumption during pregnancy.
Keywords: Artificial sweeteners; DNA integrity; Dose-dependent; Inflammation; Neurobehavioral performance; Oxidative stress.