A transient placental source of serotonin for the fetal forebrain

• Published in: Nature (London) 2011-04, Vol.472 (7343), p.347-350
• Main Authors: Bonnin, Alexandre, Goeden, Nick, Chen, Kevin, Wilson, Melissa L., King, Jennifer, Shih, Jean C., Blakely, Randy D., Deneris, Evan S., Levitt, Pat
• Format: Article
• Language: English
• Subjects: 631/136/368; 631/378/1697; 631/378/548/1964; Animals; Autism; Biological and medical sciences; Brain; Colleges & universities; Embryo, Mammalian - metabolism; Female; Fetal development; Fetus - embryology; Fetus - metabolism; Fundamental and applied biological sciences. Psychology; Humanities and Social Sciences; Humans; In Vitro Techniques; letter; Maternal-Fetal Exchange - physiology; Mice; multidisciplinary; Neurons; Observations; Physiological aspects; Placenta - metabolism; Pregnancy; Prenatal Exposure Delayed Effects; Prosencephalon; Prosencephalon - embryology; Prosencephalon - metabolism; Raphe Nuclei - cytology; Rhombencephalon - embryology; Rhombencephalon - metabolism; Rodents; Science; Science (multidisciplinary); Serotonin; Serotonin - analysis; Serotonin - biosynthesis; Serotonin - metabolism; Time Factors; Transcription Factors - deficiency; Transcription Factors - genetics; Vertebrates: nervous system and sense organs
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature09972

Early sources of serotonin Although it is widely assumed that a maternal contribution to fetal serotonin (5-hydroxytryptamine or 5-HT) levels during pregnancy is important in neurodevelopment, there is little direct experimental evidence to support the idea. Bonnin et al . use new techniques to determine that during early pregnancy the placenta is a significant source of 5-HT, made from maternal tryptophan precursors in both mice and humans. Later in pregnancy, an endogenous 5-HT source in the fetus takes over. Serotonin (5-hydroxytryptamine or 5-HT) is thought to regulate neurodevelopmental processes through maternal–fetal interactions that have long-term mental health implications. It is thought that beyond fetal 5-HT neurons there are significant maternal contributions to fetal 5-HT during pregnancy 1 , 2 but this has not been tested empirically. To examine putative central and peripheral sources of embryonic brain 5-HT, we used Pet1 −/− (also called Fev) mice in which most dorsal raphe neurons lack 5-HT 3 . We detected previously unknown differences in accumulation of 5-HT between the forebrain and hindbrain during early and late fetal stages, through an exogenous source of 5-HT which is not of maternal origin. Using additional genetic strategies, a new technology for studying placental biology ex vivo and direct manipulation of placental neosynthesis, we investigated the nature of this exogenous source. We uncovered a placental 5-HT synthetic pathway from a maternal tryptophan precursor in both mice and humans. This study reveals a new, direct role for placental metabolic pathways in modulating fetal brain development and indicates that maternal–placental–fetal interactions could underlie the pronounced impact of 5-HT on long-lasting mental health outcomes.