Human amniocytes regulate serotonin levels by active uptake and express genes suggestive of a wider role in facilitating neurotransmitter regulation in the fetal environment.
Fetal serotonin levels, which mediate multiple developmental processes, are highly regulated. However, an incomplete picture exists on the component parts of such regulation during fetal growth. Serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) are found in the amniotic fluid, also containing significant numbers of amniocytes, previously thought to be the result of cell shedding as a byproduct of growth. The aim of the present study was to examine human amniocytes as a potentially active and dynamic component of serotonin regulation in the fetal environment. Using amniocytes derived from multiple donors of amniocentesis, we found all components necessary for serotonin metabolism. We identified a strong expression of the serotonin transporter and confirmed the high-affinity serotonin transporter-mediated uptake of serotonin (5-HT), along with uptake via the norepinephrine transporter, and an evidence of 5-HT breakdown due to the expression of the degradative enzymes monoamine oxidase A and B. Additionally, wider expression analysis for biogenic amine and cholinergic metabolism suggests a capability for cholinergic synthesis and release and for catecholamine storage. Our results shed new light on amniocytes, consistent with a role in the homeostasis of neurotransmitters during fetal development. Moreover, these results may provide clinical significance for amniocytes as new targets for uptake inhibitors such as tricyclic antidepressants, selective serotonin reuptake inhibitors, and drugs of abuse such as cocaine, with implications on their regulation during pregnancy. This work shows for the first time an inherent in vivo function of amniocytes and more broadly implicates them as a new and active component of the fetal-maternal regulatory system.
Laboratory of Developmental Neurobiology, School of Biomolecular and Biomedical Sciences, University College Dublin, Conway Institute, Dublin, Ireland.
Shona
S
Pfeiffer
Julia
J
Boyle
Sean
S
Daly
Eilís
E
Dowd
Jana
J
Haase
David
D
McLaughlin
D000653:Amniotic Fluid / Q000166:cytology / Q000502:physiology*; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011247:Pregnancy; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism; D050494:Vesicular Acetylcholine Transport Proteins / Q000235:genetics / Q000378:metabolism
D017077:Culture Media, Conditioned; D018377:Neurotransmitter Agents; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D050494:Vesicular Acetylcholine Transport Proteins; D012701:Serotonin; C497467:TPH1 protein, human; D014365:Tryptophan Hydroxylase; D008995:Monoamine Oxidase; D001142:Aromatic-L-Amino-Acid Decarboxylases