Medium and long-term effects of low doses of Chlorpyrifos during the postnatal, preweaning developmental stage on sociability, dominance, gut microbiota and plasma metabolites

Cristian Perez-Fernandez; Miguel Morales-Navas; Luis Manuel Aguilera-Sáez; Ana Cristina Abreu; Laia Guardia-Escote; Ignacio Fernández; José Antonio Garrido-Cárdenas; María Teresa Colomina; Estela Giménez; Fernando Sánchez-Santed

doi:10.1016/j.envres.2020.109341

Medium and long-term effects of low doses of Chlorpyrifos during the postnatal, preweaning developmental stage on sociability, dominance, gut microbiota and plasma metabolites

Environ Res. 2020 May:184:109341. doi: 10.1016/j.envres.2020.109341. Epub 2020 Mar 6.

Affiliations

¹ Department of Psychology and Health Research Center, University of Almería, Ctra. Sacramento, s/n, 04120, Almería, Spain. Electronic address: cpf603@ual.es.
² Department of Psychology and Health Research Center, University of Almería, Ctra. Sacramento, s/n, 04120, Almería, Spain. Electronic address: miguelmoralesnavas@gmail.com.
³ Department of Chemistry and Physics, Research Centre CIAIMBITAL, University of Almería, Ctra. Sacramento, s/n, 04120, Almería, Spain. Electronic address: luisma8883@hotmail.com.
⁴ Department of Chemistry and Physics, Research Centre CIAIMBITAL, University of Almería, Ctra. Sacramento, s/n, 04120, Almería, Spain. Electronic address: acabreu@ual.es.
⁵ Department of Biochemistry and Biotechnology and Research in Neurobehavior and Health (NEUROLAB), Universitat Rovira i Virgili, 43007, C/ Macel.lí Domingo 1, Tarragona, Spain. Electronic address: laia.guardia@urv.cat.
⁶ Department of Chemistry and Physics, Research Centre CIAIMBITAL, University of Almería, Ctra. Sacramento, s/n, 04120, Almería, Spain. Electronic address: ifernan@ual.es.
⁷ Central Research Services, University of Almería, Ctra. Sacramento, s/n, 04120, Almería, Spain. Electronic address: jcardena@ual.es.
⁸ Department of Psychology and Research Center for Behavior Assessment (CRAMC), Universitat Rovira i Virgili, 43007, C/ Carretera de Valls, s/n, Tarragona, Spain. Electronic address: mariateresa.colomina@urv.cat.
⁹ Department of Biology and Geology, University of Almería, Ctra. Sacramento, s/n, 04120, Almería, Spain. Electronic address: estela@ual.es.
¹⁰ Department of Psychology and Health Research Center, University of Almería, Ctra. Sacramento, s/n, 04120, Almería, Spain. Electronic address: fsanchez@ual.es.

PMID: 32179266
DOI: 10.1016/j.envres.2020.109341

Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental pathology characterized by altered verbalizations, reduced social interaction behavior, and stereotypies. Environmental factors have been associated with its development. Some researchers have focused on pesticide exposure. Chlorpyrifos (CPF) is the most used Organophosphate. Previous developmental studies with CPF showed decreased, enhanced or no effect on social outcomes eminently in mice. The study of CPF exposure during preweaning stages on social behavior is sparse in mice and non-existent in rats. d stressors could be at the basis of ASD development, and around postnatal day 10 in the rat is equivalent to the human birthday in neurodevelopmental terms. We explored the effects of exposure to low doses (1mg/kg/mL/day) of CPF during this stage regarding: sociability, dominance gut microbiome and plasma metabolomic profile, since alterations in these systems have also been linked to ASD. There was a modest influence of CPF on social behavior in adulthood, with null effects during adolescence. Dominance and hierarchical status were not affected by exposure. Dominance status explained the significant reduction in reaction to social novelty observed on the sociability test. CPF induced a significant gut microbiome dysbiosis and triggered a hyperlipidemic, hypoglycemic/hypogluconeogenesis and a general altered cell energy production in females. These behavioral results in rats extend and complement previous studies with mice and show novel influences on gut metagenomics and plasma lipid profile and metabolomics, but do not stablish a relation between the exposure to CPF and the ASD phenotype. The effects of dominance status on reaction to social novelty have an important methodological meaning for future research on sociability.

Keywords: ASD; Chlorpyrifos; Development; Dominance; Evidence of approval (animals); Gut microbiota; Metabolomics; Sociability.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Animals
Autism Spectrum Disorder* / chemically induced
Chlorpyrifos* / toxicity
Female
Gastrointestinal Microbiome*
Humans
Insecticides* / toxicity
Mice
Rats
Social Behavior

Substances

Insecticides
Chlorpyrifos