Prenatal Serotonin Fluctuation Affects Serotoninergic Development and Related Neural Circuits in Chicken Embryos

Abstract

The placenta is the primary source of serotonin for fetal development, programming fetal neural wiring in humans and other mammals. The fluctuation in maternal serotonin affects fetal neurogenesis with life-long consequences, however, its mechanisms have not been well known. The chicken embryo, independent of maternal neurohormonal influence, may offer an ideal model for studying the mechanisms of prenatal serotonin exposure altering postnatal physiological homeostasis and behavioral exhibition. To investigate the fine-tuning of serotonin to the early embryonic neurodevelopment, 10 µg and 20 µg serotonin were secretively injected to chicken embryos before incubation. Serotonin exposure mainly affected the neural development in the pons and midbrain, altered the serotoninergic and dopaminergic neuronal morphology, nucleus distribution, and their metabolisms and related gene expressions. The comprehensive effect of serotonin exposure was not dosage-dependent but the working pathways differed, 10 µg serotonin exposure reduced serotonin turnover rate, increased serotonin 1a receptor expression, and facilitated the ventral tegmental area neuronal development; while 20 µg serotonin exposure increased the serotoninergic and dopaminergic neurotransmission and enhanced serotoninergic regulation to the hypothalamus. These findings indicate that the serotonin exposure effect can be achieved via different paths by modifying the embryonic serotonergic and dopaminergic systems and altering fetal serotonergic influence on the thalamocortical circuit and hypothalamic-pituitary-adrenal axis. These results may offer a novel sight for understanding the function of serotonin during neurodevelopment and raise the possibility for using selective serotonin reuptake inhibitors to regulate emotional and mental wellness during early pregnancy and possible risks of complications for babies.