Back to Search Start Over

Characterization of a human placental clearance system to regulate serotonin levels in the fetoplacental unit.

Characterization of a human placental clearance system to regulate serotonin levels in the fetoplacental unit.

Authors :
Staud F
Pan X
Karahoda R
Dong X
Kastner P
Horackova H
Vachalova V
Markert UR
Abad C
Source :
Reproductive biology and endocrinology : RB&E [Reprod Biol Endocrinol] 2023 Aug 23; Vol. 21 (1), pp. 74. Date of Electronic Publication: 2023 Aug 23.
Publication Year :
2023

Abstract

Background: Serotonin (5-HT) is a biogenic monoamine with diverse functions in multiple human organs and tissues. During pregnancy, tightly regulated levels of 5-HT in the fetoplacental unit are critical for proper placental functions, fetal development, and programming. Despite being a non-neuronal organ, the placenta expresses a suite of homeostatic proteins, membrane transporters and metabolizing enzymes, to regulate monoamine levels. We hypothesized that placental 5-HT clearance is important for maintaining 5-HT levels in the fetoplacental unit. We therefore investigated placental 5-HT uptake from the umbilical circulation at physiological and supraphysiological levels as well as placental metabolism of 5-HT to 5-hydroxyindoleacetic acid (5-HIAA) and 5-HIAA efflux from trophoblast cells.<br />Methods: We employed a systematic approach using advanced organ-, tissue-, and cellular-level models of the human placenta to investigate the transport and metabolism of 5-HT in the fetoplacental unit. Human placentas from uncomplicated term pregnancies were used for perfusion studies, culturing explants, and isolating primary trophoblast cells.<br />Results: Using the dually perfused placenta, we observed a high and concentration-dependent placental extraction of 5-HT from the fetal circulation. Subsequently, within the placenta, 5-HT was metabolized to 5-hydroxyindoleacetic acid (5-HIAA), which was then unidirectionally excreted to the maternal circulation. In the explant cultures and primary trophoblast cells, we show concentration- and inhibitor-dependent 5-HT uptake and metabolism and subsequent 5-HIAA release into the media. Droplet digital PCR revealed that the dominant gene in all models was MAO-A, supporting the crucial role of 5-HT metabolism in placental 5-HT clearance.<br />Conclusions: Taken together, we present transcriptional and functional evidence that the human placenta has an efficient 5-HT clearance system involving (1) removal of 5-HT from the fetal circulation by OCT3, (2) metabolism to 5-HIAA by MAO-A, and (3) selective 5-HIAA excretion to the maternal circulation via the MRP2 transporter. This synchronized mechanism is critical for regulating 5-HT in the fetoplacental unit; however, it can be compromised by external insults such as antidepressant drugs.<br /> (© 2023. BioMed Central Ltd., part of Springer Nature.)

Details

Language :
English
ISSN :
1477-7827
Volume :
21
Issue :
1
Database :
MEDLINE
Journal :
Reproductive biology and endocrinology : RB&E
Publication Type :
Academic Journal
Accession number :
37612712
Full Text :
https://doi.org/10.1186/s12958-023-01128-z