en Neurophysiology/Pharmacology Neurophysiology/Pharmacology Review Review <p><span style="font-size:12px;"><span style="font-family:Arial;">Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by deficits in social interaction, communication challenges, and repetitive behaviors. Its etiology is multifactorial, involving interactions among genetic, epigenetic, and environmental factors. Recent studies have revealed that environmental pollutants, immune dysregulation, mitochondrial dysfunction, oxidative stress, and epigenetic alterations play significant roles in the development of ASD. Exposure to environmental toxins such as heavy metals and air pollutants has been linked to an increased risk of ASD, primarily by inducing oxidative stress, neuroinflammation, and neurotoxicity. Immune dysregulation, marked by abnormal immune responses, may also contribute to neurodevelopmental alterations observed in ASD. Mitochondrial dysfunction, resulting in impaired energy metabolism and elevated oxidative stress, is frequently reported in individuals with ASD. In addition, epigenetic mechanisms such as DNA methylation and histone modifications are crucial for regulating gene expression and can be influenced by environmental exposures. Individuals with ASD exhibit abnormal epigenetic patterns, indicating that environmental factors can influence gene function without modifying the genetic code. The higher prevalence of ASD in males indicates potential sex-specific susceptibilities and points to a complex gene&ndash;environment interaction. While genetic predisposition is a major factor, environmental influences may intensify or reduce the risk. Understanding these interconnected mechanisms is vital for developing improved diagnostic tools, early interventions, and effective therapies. Future research should aim to identify specific biomarkers and molecular targets, enabling personalized approaches to ASD management. A deeper understanding of these mechanisms offers promising pathways for prevention, early detection, and treatment of ASD.</span></span></p> Adaptive immunity,Autism spectrum disorder (ASD),Environmental contaminants,Epigenetic,Neurodevelopmental disorders 10 21 http://ppj.phypha.ir/browse.php?a_code=A-10-1574-2&slc_lang=en&sid=1 Hussein A. Ghanimi husseinalawi86@gmail.com 3200319475328460039137 3200319475328460039137 No 1. College of Nursing, University of Al-Ameed, Karbala, Iraq.2. Department of Clinical Laboratories, College of Applied Medical Sciences, University of Kerbala, Karbala, Iraq. 3. Stem Cell Center, Al-Kafeel Super Specialty Hospital, Karbala, Iraq Abdullah H. Maad AbdullahMaad1234@gmail.com 3200319475328460039138 3200319475328460039138 No Department of pharmaceutics, College of pharmacy, University of Al-Ameed, Karbala, Iraq Zhikal Omar Khudhur ZhikalOmarKhudhur1@gmail.com 3200319475328460039139 3200319475328460039139 No Biology Education Department, Tishk International University, Erbil, Iraq Aida Karimian AidaKarimian1364@gmail.com 3200319475328460039140 3200319475328460039140 No Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran Aida Nahumi AidaNahumikl@gmail.com 3200319475328460039141 3200319475328460039141 No Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran. Asadollah Asadi AsadollahAsadi1345@gmil.com 3200319475328460039142 3200319475328460039142 No Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran. Hasan Taheri Hasan23Taheri@gmail.com 3200319475328460039143 3200319475328460039143 No Faculty of Psychology and Educational Sciences, Allameh Tabataba'i University, Tehran, Iran. Arash Abdolmaleki abdolmalekiarash1364@gmail.com 3200319475328460039144 0000000328584098 Yes Department of Biophysics, Faculty of Advanced Technologies, University of Mohaghegh Ardabili, Namin, Iran.