Abstract
Autism spectrum disorders (ASD) are neurodevelopmental pathologies. Investigating both sexes is crucial for understanding sex-specific manifestations of ASD. This study aims to examine ASD-like behaviours and metabolic alterations in male and female rats prenatally exposed to valproic acid (VPA). Pregnant Wistar albino rats were administered 400 mg/kg VPA or saline on embryonic day 12. Pups were subjected to various behavioural tests, including olfactory discrimination, sociability, locomotion, anxiety and exploratory behaviour assessments. On postnatal day 35, pups were sacrificed, and blood glucose levels were measured. Serum and brain leptin, orexin-A, nesfatin-1 and ghrelin levels were assessed by the ELISA method. VPA-exposed pups exhibited increased latency to reach maternal bedding, reduced sociability, decreased locomotion and increased immobility in both sexes. In the elevated plus maze, VPA-exposed females showed an increase in open-arm entries, while males showed a reduction compared to control groups. Blood glucose levels were significantly elevated in VPA-exposed males but not females. Significant sex-independent changes were observed in serum and brain levels of leptin and nesfatin-1 in the VPA groups. Brain orexin-A and serum ghrelin levels were altered in the VPA group in a sex-dependent manner. Prenatal VPA exposure induces ASD-like symptoms in both sexes, with notable sex-specific differences in behaviour and metabolic regulation. These findings highlight the importance of including both sexes in ASD research to better understand sex-dependent characteristics of the disorder, particularly concerning metabolic dysregulation.