Environmental factors may contribute to autism development and male bias: Effects of fragrances on developing neurons

Autism spectrum disorders (ASDs) are developmental conditions characterized by deficits in social interaction, impairments in verbal and nonverbal communication, and stereotyped patterns of behavior. Previous studies have implicated environmental factors in the development of ASD. Although no reliable neurophysiological network is associated with ASD, low levels of plasma oxytocin (OXY) and arginine vasopressin (AVP) have been reported. The "twin" nonapeptides OXY and AVP are mainly produced in the brain of mammals, and dysregulation of these neuropeptides has been associated with changes in behavior, especially social interactions.

Previously, we analyzed 91 commonly used fragrances and reported significant mutagenic, neurocytotoxic, and stimulatory effects on fetal neuroblastoma cell lines (NBC). In this study, we analyzed the neuromodifications of three selected fragrances on male and female human fetal brain neurons, utilizing immunohistochemistry.

We show that exposure to femtomolar concentrations of fragrances results in morphological changes by light microscopy in the NBC. Importantly, these fragrances significantly reduced the OXY- and AVP-receptor positive (OXYR+ and AVPR+) neurons in male NBC but not in female NBC, possibly contributing to the development of male bias in ASD.

This study is the first to show a potential link between fragrance exposure, depletion of OXYR+ and AVPR+ neurons, and a male bias in autism.