Disrupted placental serotonin synthetic pathway and increased placental serotonin

Potential implications in the pathogenesis of human fetal growth restriction

Suveena Ranzil, Stacey Ellery, David W. Walker, Cathy Vaillancourt, Nadia Alfaidy, Alexander Bonnin, Anthony Borg, Euan M. Wallace, Peter R. Ebeling, Jan Jaap Erwich, Padma Murthi

Research output: Contribution to journalReview ArticleResearchpeer-review

Abstract

Objectives: Placental insufficiency contributes to altered maternal-fetal amino acid transfer, and thereby to poor fetal growth. An important placental function is the uptake of tryptophan and its metabolism to serotonin (5-HT) and kynurenine metabolites, which are essential for fetal development. We hypothesised that placental 5-HT content will be increased in pregnancies affected with fetal growth restriction (FGR). Methods: The components of the 5-HT synthetic pathway were determined in chorionic villus samples (CVS) from small-for gestation (SGA) and matched control collected at 10–12 weeks of human pregnancy; and in placentae from third trimester FGR and gestation-matched control pregnancies using the Fluidigm Biomarker array for mRNA expression, the activity of the enzyme TPH and 5-HT concentrations using an ELISA. Results: Gene expression for the rate limiting enzymes, TPH1 and TPH2; 5-HT transporter, SLC6A4; and 5-HT receptors HTR5A, HTR5B, HTR1D and HTR1E were detected in all CVS and third trimester placentae. No significant difference in mRNA was observed in SGA compared with control. Although there was no significant change in TPH1 mRNA, the mRNA of TPH2 and SLC6A4 was significantly decreased in FGR placentae (p < 0.05), while 5-HT receptor mRNA was significantly increased in FGR compared with control (p < 0.01). Placental TPH enzyme activity was significantly increased with a concomitant increase in the total placental 5-HT concentrations in FGR compared with control. Conclusion: This study reports differential expression and activity of the key components of the 5-HT synthetic pathway associated with the pathogenesis of FGR. Further studies are required to elucidate the functional consequences of increased placental 5-HT in FGR pregnancies.

Original languageEnglish
Number of pages10
JournalPlacenta
DOIs
Publication statusAccepted/In press - 23 May 2019

Cite this

@article{578c32103cba49e0adff8f26dc7df1f7,
title = "Disrupted placental serotonin synthetic pathway and increased placental serotonin: Potential implications in the pathogenesis of human fetal growth restriction",
abstract = "Objectives: Placental insufficiency contributes to altered maternal-fetal amino acid transfer, and thereby to poor fetal growth. An important placental function is the uptake of tryptophan and its metabolism to serotonin (5-HT) and kynurenine metabolites, which are essential for fetal development. We hypothesised that placental 5-HT content will be increased in pregnancies affected with fetal growth restriction (FGR). Methods: The components of the 5-HT synthetic pathway were determined in chorionic villus samples (CVS) from small-for gestation (SGA) and matched control collected at 10–12 weeks of human pregnancy; and in placentae from third trimester FGR and gestation-matched control pregnancies using the Fluidigm Biomarker array for mRNA expression, the activity of the enzyme TPH and 5-HT concentrations using an ELISA. Results: Gene expression for the rate limiting enzymes, TPH1 and TPH2; 5-HT transporter, SLC6A4; and 5-HT receptors HTR5A, HTR5B, HTR1D and HTR1E were detected in all CVS and third trimester placentae. No significant difference in mRNA was observed in SGA compared with control. Although there was no significant change in TPH1 mRNA, the mRNA of TPH2 and SLC6A4 was significantly decreased in FGR placentae (p < 0.05), while 5-HT receptor mRNA was significantly increased in FGR compared with control (p < 0.01). Placental TPH enzyme activity was significantly increased with a concomitant increase in the total placental 5-HT concentrations in FGR compared with control. Conclusion: This study reports differential expression and activity of the key components of the 5-HT synthetic pathway associated with the pathogenesis of FGR. Further studies are required to elucidate the functional consequences of increased placental 5-HT in FGR pregnancies.",
author = "Suveena Ranzil and Stacey Ellery and Walker, {David W.} and Cathy Vaillancourt and Nadia Alfaidy and Alexander Bonnin and Anthony Borg and Wallace, {Euan M.} and Ebeling, {Peter R.} and Erwich, {Jan Jaap} and Padma Murthi",
year = "2019",
month = "5",
day = "23",
doi = "10.1016/j.placenta.2019.05.012",
language = "English",
journal = "Placenta",
issn = "0143-4004",
publisher = "W.B. Saunders",

}

Disrupted placental serotonin synthetic pathway and increased placental serotonin : Potential implications in the pathogenesis of human fetal growth restriction. / Ranzil, Suveena; Ellery, Stacey; Walker, David W.; Vaillancourt, Cathy; Alfaidy, Nadia; Bonnin, Alexander; Borg, Anthony; Wallace, Euan M.; Ebeling, Peter R.; Erwich, Jan Jaap; Murthi, Padma.

In: Placenta, 23.05.2019.

Research output: Contribution to journalReview ArticleResearchpeer-review

TY - JOUR

T1 - Disrupted placental serotonin synthetic pathway and increased placental serotonin

T2 - Potential implications in the pathogenesis of human fetal growth restriction

AU - Ranzil, Suveena

AU - Ellery, Stacey

AU - Walker, David W.

AU - Vaillancourt, Cathy

AU - Alfaidy, Nadia

AU - Bonnin, Alexander

AU - Borg, Anthony

AU - Wallace, Euan M.

AU - Ebeling, Peter R.

AU - Erwich, Jan Jaap

AU - Murthi, Padma

PY - 2019/5/23

Y1 - 2019/5/23

N2 - Objectives: Placental insufficiency contributes to altered maternal-fetal amino acid transfer, and thereby to poor fetal growth. An important placental function is the uptake of tryptophan and its metabolism to serotonin (5-HT) and kynurenine metabolites, which are essential for fetal development. We hypothesised that placental 5-HT content will be increased in pregnancies affected with fetal growth restriction (FGR). Methods: The components of the 5-HT synthetic pathway were determined in chorionic villus samples (CVS) from small-for gestation (SGA) and matched control collected at 10–12 weeks of human pregnancy; and in placentae from third trimester FGR and gestation-matched control pregnancies using the Fluidigm Biomarker array for mRNA expression, the activity of the enzyme TPH and 5-HT concentrations using an ELISA. Results: Gene expression for the rate limiting enzymes, TPH1 and TPH2; 5-HT transporter, SLC6A4; and 5-HT receptors HTR5A, HTR5B, HTR1D and HTR1E were detected in all CVS and third trimester placentae. No significant difference in mRNA was observed in SGA compared with control. Although there was no significant change in TPH1 mRNA, the mRNA of TPH2 and SLC6A4 was significantly decreased in FGR placentae (p < 0.05), while 5-HT receptor mRNA was significantly increased in FGR compared with control (p < 0.01). Placental TPH enzyme activity was significantly increased with a concomitant increase in the total placental 5-HT concentrations in FGR compared with control. Conclusion: This study reports differential expression and activity of the key components of the 5-HT synthetic pathway associated with the pathogenesis of FGR. Further studies are required to elucidate the functional consequences of increased placental 5-HT in FGR pregnancies.

AB - Objectives: Placental insufficiency contributes to altered maternal-fetal amino acid transfer, and thereby to poor fetal growth. An important placental function is the uptake of tryptophan and its metabolism to serotonin (5-HT) and kynurenine metabolites, which are essential for fetal development. We hypothesised that placental 5-HT content will be increased in pregnancies affected with fetal growth restriction (FGR). Methods: The components of the 5-HT synthetic pathway were determined in chorionic villus samples (CVS) from small-for gestation (SGA) and matched control collected at 10–12 weeks of human pregnancy; and in placentae from third trimester FGR and gestation-matched control pregnancies using the Fluidigm Biomarker array for mRNA expression, the activity of the enzyme TPH and 5-HT concentrations using an ELISA. Results: Gene expression for the rate limiting enzymes, TPH1 and TPH2; 5-HT transporter, SLC6A4; and 5-HT receptors HTR5A, HTR5B, HTR1D and HTR1E were detected in all CVS and third trimester placentae. No significant difference in mRNA was observed in SGA compared with control. Although there was no significant change in TPH1 mRNA, the mRNA of TPH2 and SLC6A4 was significantly decreased in FGR placentae (p < 0.05), while 5-HT receptor mRNA was significantly increased in FGR compared with control (p < 0.01). Placental TPH enzyme activity was significantly increased with a concomitant increase in the total placental 5-HT concentrations in FGR compared with control. Conclusion: This study reports differential expression and activity of the key components of the 5-HT synthetic pathway associated with the pathogenesis of FGR. Further studies are required to elucidate the functional consequences of increased placental 5-HT in FGR pregnancies.

UR - http://www.scopus.com/inward/record.url?scp=85066615806&partnerID=8YFLogxK

U2 - 10.1016/j.placenta.2019.05.012

DO - 10.1016/j.placenta.2019.05.012

M3 - Review Article

JO - Placenta

JF - Placenta

SN - 0143-4004

ER -