Environmental exposure to chlorpyrifos during gestation, APOE polymorphism and the risk on autistic-like behaviors

Judit Biosca-Brull; Pia Basaure; Laia Guardia-Escote; Maria Cabré; Jordi Blanco; Miguel Morales-Navas; Fernando Sánchez-Santed; Maria Teresa Colomina

doi:10.1016/j.envres.2023.116969

Environmental exposure to chlorpyrifos during gestation, APOE polymorphism and the risk on autistic-like behaviors

Environ Res. 2023 Nov 15;237(Pt 2):116969. doi: 10.1016/j.envres.2023.116969. Epub 2023 Aug 31.

Authors

Judit Biosca-Brull¹, Pia Basaure², Laia Guardia-Escote², Maria Cabré³, Jordi Blanco⁴, Miguel Morales-Navas⁵, Fernando Sánchez-Santed⁵, Maria Teresa Colomina⁶

Affiliations

¹ Universitat Rovira i Virgili, Research Group in Neurobehavior and Health (NEUROLAB), Tarragona, Spain; Universitat Rovira i Virgili, Department of Psychology and Research Center for Behavior Assessment (CRAMC), Tarragona, Spain; Universitat Rovira i Virgili, Center of Environmental, Food and Toxicological Technology (TECNATOX), Reus, Spain. Electronic address: judit.biosca@urv.cat.
² Universitat Rovira i Virgili, Research Group in Neurobehavior and Health (NEUROLAB), Tarragona, Spain.
³ Universitat Rovira i Virgili, Research Group in Neurobehavior and Health (NEUROLAB), Tarragona, Spain; Universitat Rovira i Virgili, Department of Biochemistry and Biotechnology, Tarragona, Spain.
⁴ Universitat Rovira i Virgili, Research Group in Neurobehavior and Health (NEUROLAB), Tarragona, Spain; Universitat Rovira i Virgili, Center of Environmental, Food and Toxicological Technology (TECNATOX), Reus, Spain; Universitat Rovira i Virgili, Department of Basic Medical Sciences, Reus, Spain.
⁵ Department of Psychology, Health Research Center (CEINSA), Almeria University, 04120, Almeria, Spain.
⁶ Universitat Rovira i Virgili, Research Group in Neurobehavior and Health (NEUROLAB), Tarragona, Spain; Universitat Rovira i Virgili, Department of Psychology and Research Center for Behavior Assessment (CRAMC), Tarragona, Spain; Universitat Rovira i Virgili, Center of Environmental, Food and Toxicological Technology (TECNATOX), Reus, Spain. Electronic address: mariateresa.colomina@urv.cat.

PMID: 37659636
DOI: 10.1016/j.envres.2023.116969

Abstract

Autism spectrum disorder (ASD) encompasses several neurodevelopmental conditions characterized by communication and social impairment, as well as repetitive patterns of behavior. However, it can co-occur with other mental conditions such as anxiety. The massive use of chlorpyrifos (CPF) has been linked to the increased prevalence of developmental disorders. Likewise, ASD has also been closely linked to a wide variety of genetic factors. The aims of the present investigation are to study how gestational CPF exposure and APOE polymorphism affects communication skills, early development and mid-term anxiety-like behaviors, as well as, changes in gene expression related to the cholinergic system. C57BL/6J and humanized apoE3 and apoE4 homozygous mice were exposed to 0 or 1 mg/kg/day of CPF through the diet, from gestational day (GD) 12-18. In addition, a group of C57BL/6J females were injected subcutaneously with 300 mg/kg/day of valproic acid (VPA) on GD 12 and 13. This group was used as a positive control for studying some core and associated autism-like behaviors. Communication skills by means of ultrasonic vocalizations and physical/motor development were assessed during the preweaning period, whereas locomotor activity, anxiety-like behaviors and the gene expression of cholinergic elements were evaluated during adolescence. Our results showed that C57BL/6J mice prenatally exposed to CPF or VPA showed a decrease in body weight and a delay in eye opening. Communication and anxiety behavior were affected differently depending on treatment, while gene expression was altered by sex and treatment. In addition, none of the parameters evaluated in apoE transgenic mice exposed to CPF were affected, but there were differences between genotypes. Therefore, we suggest that prenatal CPF exposure and VPA produce divergent effects on communication and anxiety.

Keywords: APOE genotype; Anxiety; Autism; Chlorpyrifos; Cholinergic system; Development; Ultrasonic vocalizations.