The placenta is the primary source of serotonin (5-HT) for fetal development, programming fetal neural wiring in humans and other mammals. The fluctuation in maternal 5-HT 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 5-HT exposure altering postnatal physiological homeostasis and behavioral exhibition. To investigate the fine-tuning of 5-HT to the early embryonic neurodevelopment, 10 µg and 20 µg 5-HT were secretively injected to chicken embryos before incubation. 5-HT exposure mainly affected the neural development in the pons and midbrain, altered the serotoninergic and dopaminergic (DAergic) neuronal morphology, nucleus distribution, and their metabolisms and related gene expressions. The comprehensive effect of 5-HT exposure was not dosage-dependent but the working pathways differed, 10 µg 5-HT exposure reduced 5-HT turnover rate, increased 5-HT 1a receptor expression, and facilitated the ventral tegmental area neuronal development; while 20 µg 5-HT exposure increased the serotoninergic and DAergic neurotransmission and enhanced serotoninergic regulation to the hypothalamus. These findings indicate that the 5-HT exposure effect can be achieved via different paths by modifying the embryonic serotonergic (5-HTergic) and DAergic systems and altering fetal 5-HTergic influence on the thalamocortical circuit and hypothalamic-pituitary-adrenal axis. These results may offer a novel sight for understanding the function of 5-HT during neurodevelopment and raise the possibility for using selective 5-HT reuptake inhibitors to regulate emotional and mental wellness during early pregnancy and possible risks of complications for babies.
Keywords: chicken embryo; dopamine; mental health; neural circuits; prenatal serotonin exposure; serotoninergic development.
Copyright © 2021 IBRO. All rights reserved.