1. Disrupted placental serotonin synthetic pathway and increased placental serotonin
- Author
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Suveena Ranzil, Euan M. Wallace, Peter R. Ebeling, Anthony J. Borg, Stacey J. Ellery, Cathy Vaillancourt, Jan Jaap H. M. Erwich, Alexander Bonnin, Padma Murthi, Nadia Alfaidy, David W. Walker, Monash University [Clayton], Hudson Institute of Medical Research [Clayton], Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Invasion mechanisms in angiogenesis and cancer (IMAC), Biologie du Cancer et de l'Infection (BCI ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Keck School of Medicine [Los Angeles], University of Southern California (USC), The Royal Women's Hospital, University of Groningen [Groningen], University of Melbourne, This work was supported by an award to PM and PRE from the Australian Institute of Musculoskeletal Science, Western Health, Victoria, Australia., Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), and Reproductive Origins of Adult Health and Disease (ROAHD)
- Subjects
Adult ,0301 basic medicine ,Serotonin ,Placenta ,Pregnancy Trimester, Third ,ENDOMETRIUM ,Intrauterine growth restriction ,INFANTS ,Placental insufficiency ,Tryptophan Hydroxylase ,Biology ,Article ,Preeclampsia ,Andrology ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,medicine ,PREGNANCIES ,Humans ,Serotonin Plasma Membrane Transport Proteins ,[SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health ,Fetus ,Fetal Growth Retardation ,030219 obstetrics & reproductive medicine ,TPH1 ,CONSEQUENCES ,TPH2 ,Obstetrics and Gynecology ,Placental Insufficiency ,medicine.disease ,VESICULAR MONOAMINE TRANSPORTER ,RELATIVE GENE-EXPRESSION ,Up-Regulation ,PREECLAMPSIA ,030104 developmental biology ,medicine.anatomical_structure ,Reproductive Medicine ,Case-Control Studies ,Chorionic villi ,Gestation ,UPDATE ,Female ,IMPLANTATION ,VILLOUS TREE ,Metabolic Networks and Pathways ,Developmental Biology - 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 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.
- Published
- 2019