Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2026
High-dose prenatal omega-3 fish oil induces autism-like social deficits and hippocampal glial changes in rat offspring.
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Erdoğan Mümin Alper, Erbaş Oytun
Аннотация
OBJECTIVE: To determine whether very high-dose maternal omega-3 fish oil supplementation induces sex-dependent autism-related behavioral and neurobiological changes in rat offspring.
METHODS: Pregnant Sprague-Dawley rats received tap water or fish oil (60% EPA, 40% DHA; 5000 mg/kg/day) throughout gestation. Litters were standardized at birth and offspring weaned on P21. At P50, sociability (three-chamber test) and locomotion (open field) were assessed. Brain IGF-1, plasma biochemical markers, and serum testosterone were measured. Hippocampal CA1/CA3 neurons and GFAP immunoreactivity were analyzed.
RESULTS: Omega-3-exposed males showed a profound sociability deficit (15.4 ± 4.8% vs. 78.3 ± 6.1%; p < 0.001), while females were unaffected. Locomotor activity was unchanged. IGF-1 increased in both sexes, with a greater rise in males. Prenatal omega-3 elevated triglycerides, uric acid, and ALT in both sexes and selectively increased cholesterol and testosterone in males. Histology revealed CA1 neuronal alterations and marked astrogliosis in exposed males.
CONCLUSION: Very high-dose prenatal omega-3 intake produces a male-specific autism-like phenotype associated with IGF-1 upregulation, hippocampal glial activation, and metabolic changes, underscoring the importance of defining upper safety thresholds for prenatal omega-3 intake during pregnancy.
METHODS: Pregnant Sprague-Dawley rats received tap water or fish oil (60% EPA, 40% DHA; 5000 mg/kg/day) throughout gestation. Litters were standardized at birth and offspring weaned on P21. At P50, sociability (three-chamber test) and locomotion (open field) were assessed. Brain IGF-1, plasma biochemical markers, and serum testosterone were measured. Hippocampal CA1/CA3 neurons and GFAP immunoreactivity were analyzed.
RESULTS: Omega-3-exposed males showed a profound sociability deficit (15.4 ± 4.8% vs. 78.3 ± 6.1%; p < 0.001), while females were unaffected. Locomotor activity was unchanged. IGF-1 increased in both sexes, with a greater rise in males. Prenatal omega-3 elevated triglycerides, uric acid, and ALT in both sexes and selectively increased cholesterol and testosterone in males. Histology revealed CA1 neuronal alterations and marked astrogliosis in exposed males.
CONCLUSION: Very high-dose prenatal omega-3 intake produces a male-specific autism-like phenotype associated with IGF-1 upregulation, hippocampal glial activation, and metabolic changes, underscoring the importance of defining upper safety thresholds for prenatal omega-3 intake during pregnancy.