Effects of prenatal Firemaster 550 exposure on placental gene expression and serotonergic innervation in the developing forebrain

Project Summary Gestation is a critical window during which chemical exposure may lead to profound impacts on neurodevelopment and behavior. The placenta provides important supportive functions for the developing brain, including the secretion of hormones, monoamines and other growth factors which nurture the developing brain. Following the phase out of polybrominated diphenyl ethers (PBDEs) alternative chemical flame retardants (FRs) have become ubiquitous contaminants in the home but their toxicity remains largely unknown. We have shown that the alternative mixture known as Firemaster® 550 (FM 550) is a developmental neuroendocrine disruptor that has sex specific impacts on behavior. Almost nothing is known about the mechanisms by which FM 550 can impact the developing brain. Our preliminary data suggest disruption of placental function may play a role. Therefore the proposed studies seek to establish a novel connection between altered placental function and brain development as potential mechanism by which FM 550 impacts the developing brain. Aim 1 will test the hypothesis that prenatal FM 550 exposure sex-specifically reduces forebrain serotonin innervation. Aim 2 will test the hypothesis that the placenta is a direct target of toxicity by testing for depleted serotonin synthesis and secretion during late gestation. This aim will focus specifically on the syncytiotrophoblast cell layer, which is the primary source of serotonin for the fetal brain during late gestation. Importantly, these studies will use a dose range of FM 550 considered environmentally relevant. These experiments will be the first to study the impact of FM 550 on the placenta and gestational brain, and stand out in terms of innovation because they will be among the first to establish a direct connection between chemical induced placental dysfunction and altered brain development.