title: A transient placental source of serotonin for the fetal forebrain.
abstract: 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 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. 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.
authors.affiliation: Zilkha Neurogenetic Institute, Keck School of Medicine of USC, Los Angeles, California 90089, USA. bonnin@usc.edu
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bonnin
authors.forename: Nick
authors.initials: N
authors.lastname: Goeden
authors.forename: Kevin
authors.initials: K
authors.lastname: Chen
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Wilson
authors.forename: Jennifer
authors.initials: J
authors.lastname: King
authors.forename: Jean C
authors.initials: JC
authors.lastname: Shih
authors.forename: Randy D
authors.initials: RD
authors.lastname: Blakely
authors.forename: Evan S
authors.initials: ES
authors.lastname: Deneris
authors.forename: Pat
authors.initials: P
authors.lastname: Levitt
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000196:embryology / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D051379:Mice; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016548:Prosencephalon / Q000196:embryology* / Q000378:metabolism*; D011903:Raphe Nuclei / Q000166:cytology; D012249:Rhombencephalon / Q000196:embryology / Q000378:metabolism; D012701:Serotonin / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics
chemical_list: C484684:Fev protein, mouse; D014157:Transcription Factors; D012701:Serotonin