Aspartame intake during pregnancy induces placental dysfunction through impaired mitochondrial function and biogenesis modulation

Introduction: Aspartame is a nonnutritive sweetener (NSS), which is widely used in foods and beverages worldwide. The safety of aspartame, a commonly used artificial sweetener, has been debated. Here, we investigated the potential effects and underlying mechanisms of aspartame consumption during pregnancy on placental dysfunction and birth outcomes. Methods: Female Sprague Dawley rats were exposed to a low (30 mg/kg) or high (60 mg/kg) dose of aspartame before and during pregnancy; moreover, we assessed placental histopathological structure, oxidative stress markers, and mitochondrial function. In addition, we explored how aspartame affects birth weight in a human maternal–infant cohort. Results: In animal study revealed that aspartame treatment of female rats for 14 weeks (12 week before pregnancy and 18 days of gestation) causes a significant reduction in the number and weight of fetuses, as well as damage to placental structure. These effects are linked to increased oxidative stress in the placenta, possibly damaging placental trophoblasts, impairing mitochondrial function, and initiating a compensatory mitochondrial biosynthesis mechanism. In the human pregnant cohort revealed that aspartame reduces birth weight considerably. Discussion: These findings suggested the potential risks associated with aspartame consumption during pregnancy. Therefore, the safety of aspartame, particularly in pregnant individuals, should be reconsidered; specifically, tailored, acceptable daily intake guidelines should be developed for aspartame in different populations.