A transient placental source of serotonin for the fetal forebrain

Nature. 2011 Apr 21;472(7343):347-50. doi: 10.1038/nature09972.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Embryo, Mammalian / metabolism
  • Female
  • Fetus / embryology
  • Fetus / metabolism*
  • Humans
  • In Vitro Techniques
  • Maternal-Fetal Exchange / physiology*
  • Mice
  • Placenta / metabolism*
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Prosencephalon / embryology*
  • Prosencephalon / metabolism*
  • Raphe Nuclei / cytology
  • Rhombencephalon / embryology
  • Rhombencephalon / metabolism
  • Serotonin / analysis
  • Serotonin / biosynthesis*
  • Serotonin / metabolism
  • Time Factors
  • Transcription Factors / deficiency
  • Transcription Factors / genetics

Substances

  • Fev protein, mouse
  • Transcription Factors
  • Serotonin