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Both genetic and environmental factors contribute to the development of ASD, with early\u2010life stressors, such as maternal separation (MS), and exposure to neurotoxic agents, like valproic acid (VPA), being key environmental contributors. This study investigates the combined impact of maternal deprivation (MD) and postnatal VPA exposure on autism\u2010like behaviours and neurodevelopmental outcomes in male and female rats. Rats exposed to MD from postnatal days 2 to 4 exhibited significant changes in social interaction and anxiety\u2010like behaviours, with female rats being more sensitive to MD than males. Postnatal VPA exposure resulted in similar behavioural alterations, including increased anxiety and social impairment, aligning with previous findings of VPA\u2010induced neurodevelopmental deficits. A combination of MD and VPA exposure exacerbated anxiety\u2010like behaviours in females, indicating that early\u2010life stress and environmental toxins can synergistically affect neurodevelopment. Our results further suggest that the impact of these exposures may differ between sexes, with females showing heightened sensitivity to both MD and VPA\u2010induced stress. These findings provide valuable insights into the complex interactions between genetic, environmental and epigenetic factors in ASD pathophysiology. The study underscores the critical role of early\u2010life stressors, such as MD, in exacerbating neurodevelopmental disorders, particularly when combined with neurotoxic environmental factors like VPA. The sex\u2010specific differences observed in behavioural outcomes suggest the importance of considering biological sex in future ASD research and therapeutic strategies.<\/jats:p>","DOI":"10.1002\/jdn.70004","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T16:52:50Z","timestamp":1741711970000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of Valproic Acid and Maternal Deprivation on Autism\u2010Like Behaviours and Neurodevelopmental Outcomes in Female and Male Rats"],"prefix":"10.1002","volume":"85","author":[{"given":"Sara","family":"Sheibani\u00a0Tezerji","sequence":"first","affiliation":[{"name":"Faculty of Veterinary Medicine Shahid Bahonar University of Kerman  Kerman Iran"},{"name":"Department of Behavioral and Molecular Neurobiology, Regensburg Center for Neuroscience University of Regensburg  Regensburg 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