title: Epigenetic effect of testosterone in the behavior of C. elegans. A clue to explain androgen-dependent autistic traits?
abstract: Current research indicates that the causes of autism spectrum disorders (ASDs) are multifactorial and include both genetic and environmental factors. To date, several works have associated ASDs with mutations in genes that encode proteins involved in neuronal synapses; however other factors and the way they can interact with the development of the nervous system remain largely unknown. Some studies have established a direct relationship between risk for ASDs and the exposure of the fetus to high testosterone levels during the prenatal stage. In this work, in order to explain possible mechanisms by which this androgenic hormone may interact with the nervous system, C. elegans was used as an experimental model. We observed that testosterone was able to alter the behavioral pattern of the worm, including the gentle touch response and the pharyngeal pumping rate. This impairment of the behavior was abolished using specific RNAi against genes orthologous to the human androgen receptor gene. The effect of testosterone was eliminated in the nhr-69 (ok1926) deficient mutant, a putative ortholog of human AR gene, suggesting that this gene encodes a receptor able to interact with the hormone. On the other hand the testosterone effect remained in the gentle touch response during four generations in the absence of the hormone, indicating that some epigenetic mechanisms could be involved. Sodium butyrate, a histone deacetylase inhibitor, was able to abolish the effect of testosterone. In addition, the lasting effect of testosterone was eliminated after the dauer stage. These results suggest that testosterone may impair the nervous system function generating transgenerational epigenetic marks in the genome. This work may provide new paradigms for understanding biological mechanisms involved in ASDs traits.
authors.affiliation: Departamento de Genética, Universidad de Córdoba, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba Córdoba, Spain.
authors.forename: M Mar
authors.initials: MM
authors.lastname: Gámez-Del-Estal
authors.affiliation: Departamento de Genética, Universidad de Córdoba, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba Córdoba, Spain.
authors.forename: Israel
authors.initials: I
authors.lastname: Contreras
authors.affiliation: Departamento de Genética, Universidad de Córdoba, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba Córdoba, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Prieto-Pérez
authors.affiliation: Departamento de Genética, Universidad de Córdoba, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba Córdoba, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ruiz-Rubio
keywords: Autism spectrum disorders (ASDs); Caenorhabditis elegans; epigenetics; gentle touch; nhr-69; nuclear hormone receptor; pharyngeal pumping; testosterone