Developmental organophosphate flame retardant exposure disrupts adult hippocampal neurogenesis in Wistar rats

Abstract

Organophosphate flame retardant (OPFR) contamination is ubiquitous and bio-monitoring studies have shown that human exposure is widespread and may be unavoidable. OPFRs bear structural similarities to known neurotoxicants such as organophosphate insecticides and have been shown to have both endocrine disrupting and developmental neurotoxic effects. The perinatal period in rodents represents a critical period in the organization of the developing nervous system and insults during this time can impart profound changes on the trajectory of neural development and function, lasting into adulthood. Adult hippocampal neurogenesis (AHN) facilitates dentate gyrus function and broader hippocampal circuit activity in adults; however, the neurogenic potential of this process in adulthood is vulnerable to disruption by exogenous factors during early life. We sought to assess the impact of OPFRs on AHN in offspring of dams exposed during gestation and lactation. Results indicate that developmental OPFR exposure has significant, sex specific impacts on multiple markers of AHN in the dentate gyrus of rats. In males, OPFR exposure significantly reduced the number of neural progenitors the number of new/immature neurons and reduced dentate gyrus volume. In females, exposure increased the number of neural progenitors, decreased the number of new/immature neurons, but had no significant effect on dentate gyrus volume. These results further elucidate the developmental neurotoxic properties of OPFRs, emphasize the long-term impact of early life OPFR exposure on neural processes, and highlight the importance of including sex as a biological variable in neurotoxicology research.