Effects of environmental toxicant exposures on oxytocin and vasopressin systems in the developing brain: factors imparting risk and resilience

Environmental toxicants are increasingly prevalent worldwide and associated with numerous neurodevelopmental and psychiatric health outcomes. Exposure to these toxicants, particularly during gestation and the early postnatal period, alters maternal and offspring stress responses, inflammation, and behavioral outcomes. Oxytocin (OT) and arginine vasopressin (AVP) are highly conserved neuropeptides with myriad roles in the regulation of social behavior, stress responses, and more. While developmental stress is well known to impact OT and AVP systems, a growing body of literature suggests that early-life exposure to toxicants also impacts OT and AVP system development. Here we review the evidence demonstrating that perinatal exposures to environmental toxicants program developmental trajectories of the OT and AVP systems. Perinatal exposure to flame retardants, pesticides, plastics, and air pollution induces a variety of changes to OT and AVP systems in the brain, affecting the neuropeptides themselves as well as their primary central receptors, the oxytocin receptor (OTR) and the vasopressin receptor 1a (V1aR), respectively. Next, we discuss two biological mechanisms of action that may underlie the effects of toxicant exposure on OT and AVP: endocrine disruption and maternal immune activation. Finally, we explore key factors that promote either risk or resilience to toxicant exposures, including psychosocial experience, sex, the gut microbiome, and dosage/timing of exposures. Cumulatively, the literature reviewed suggests that preventing psychosocial stress to mothers during the perinatal period while promoting positive psychosocial experiences may lessen the impact of toxicants on offspring outcomes. Furthermore, the gut microbiome may be an important intermediary, and therefore target for intervention, between toxicant exposures and OT and AVP systems in the brain.