Table 1.

The role and mechanisms of AhR/CYP1 pathway in ASD development.

Gene	Study Model	Study Design	AhR/CYP1 Modulator	Effect on AhR/CYP1 Pathway	Effect on Autism Incidence & Development	References
AhR	Human	SK-N-SH human-derived neurons	TCDD	AhR activation → ↓AChE	↓ Neuronal activity	[90]
			CH223191	AhR inhibitor, CH223191 → ↑ AChE	↑ Neuronal activity
		Pregnant amniotic fluids	PCBs & heavy metals	↑ AhR transactivation	↓ The levels of PFAS were lower in ASD cases compared to control.	[78]
	Rats	Perinatal exposure to TCDD	TCDD	Activation of AhR → ↓ AChE, monoamines, ↑ stimulation of GABA ↓ thyroid hormones, increase in TSH, decrease growth hormones in cerebellum of offspring	↑ Permanent brain damage. Impaired the development of cerebellum of their offspring	[89]
CYP1A	Human	Autistic subject		↓ CYP1A1 gene expression in umbilical cord blood	↑ ASD incidence compared to control	[82]
		Pregnant	Dioxin	↑ dioxin levels in maternal blood	↑ Neurodevelopmental deficits and autistic traits in the children with ASD	[63,83]
			PCDFs	↑ PCDFs levels in maternal blood	↑ Autistic traits in middle to late childhood using SRS	[61]
	Zebrafish	Developmental exposure to PCB126 on early- and later-life behavioral	PCB126	↑ CYP1A1 in early stages of development, with no significant upregulation at adulthood	Impaired short-term and long-term habituation to unfamiliar environment ↑ Anxiety-related behavior with no change in the larval locomotor activity	[91,92]
	Mice	Pregnant C57BL/6N	AhR plasmid transfection	Constitutive AhR activation	Affects neuronal migration during hippocampal development.	[84]
		High affinity Cyp1a2(−/−)	PCBs	CYP1A2 Knockout	↑ Motor dysfunction compared to wild-type mouse. ↑ Susceptibility to nigrostriatal dysfunction and motor deficit, and toxicity of the cerebellum and cortex.	[93,94]
CYP1B1	Human	Autistic children	Vitamin D deficiency	↓ CYP1B1 plasma levels by 70% through epigenetic silencing of CYP1B1	↓ Vitamin D by 60% → positively correlates with ASD	[81]