ArticleActa physiologica (Oxford, England)2020
Serotonin homeostasis in the materno-foetal interface at term: Role of transporters (SERT/SLC6A4 and OCT3/SLC22A3) and monoamine oxidase A (MAO-A) in uptake and degradation of serotonin by human and rat term placenta.
Article in Acta physiologica (Oxford, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 74 citations in OpenAlex.
- Tryptophan metabolism: A hidden regulator of female reproductive health beyond fertility.Chinese medical journal · 2026Review
- The placental tryptophan pathway across gestation: implications for pregnancy outcomes.Human reproduction update · 2026Review
- Compensatory Serotonin Synthesis and Histone H3 Serotonylation in Preimplantation Embryos Exposed to Maternal Fluoxetine or Monoamine Oxidase Blockade.Journal of developmental biology · 2026Article
- Maternal serum serotonin, serotonin transporter, and umbilical cord arterial serotonin levels in obese versus non-obese pregnancies.Northern clinics of Istanbul · 2026Article
- Sex-dependent serotonergic signaling across development: molecular mechanisms shaping vulnerability to neurodevelopmental and mental disorders.Frontiers in pharmacology · 2026Review
- Placental and fetal consequences of maternal selective serotonin reuptake inhibitor use: current evidence and unresolved questions.Frontiers in pharmacology · 2026Review
- Placental monoamine oxidase A activity in pregnancies complicated by maternal overweight/obesity and gestational diabetes mellitus.Frontiers in endocrinology · 2026Article
- Tryptophan's Journey Through Pregnancy: The Role of Serotonin.International journal of tryptophan research : IJTR · 2026Review
- Controversial effects of metformin on human physiology and pathophysiology.Frontiers in pharmacology · 2026Review
- Disruption of the Placenta-Brain Axis in Transgenic Mice Lacking Serotonin Transporter (SERT) in Trophoblast Cells.International journal of molecular sciences · 2025Article
- Persistent and Dose-Dependent Neural and Metabolic Gene Expression Changes Induced by Transient Citalopram Exposure in Zebrafish Embryos.International journal of molecular sciences · 2025Article
- Impact of intraamniotic inflammation on tryptophan metabolism in the placenta-fetal brain axis in rats.Reproduction (Cambridge, England) · 2025Article
- Placental serotonergic system dysregulation is associated with early impairments in infant neurodevelopment.Frontiers in endocrinology · 2025Article
- Taprenepag restores maternal-fetal interface homeostasis for the treatment of neurodevelopmental disorders.Journal of neuroinflammation · 2024Article
- Host 5-HT affects Plasmodium transmission in mosquitoes via modulating mosquito mitochondrial homeostasis.PLoS pathogens · 2024Article
- Monoamine oxidases activity maintains endometrial monoamine homeostasis and participates in embryo implantation and development.BMC biology · 2024Article
- Serotonin Transporter-dependent Histone Serotonylation in Placenta Contributes to the Neurodevelopmental Transcriptome.Journal of molecular biology · 2024Article
- Developmental expression of catecholamine system in the human placenta and rat fetoplacental unit.Scientific reports · 2024Article
- Sex and fetal genome influence gene expression in pig endometrium at the end of gestation.BMC genomics · 2024Article
- A Review of Serotonin in the Developing Lung and Neonatal Pulmonary Hypertension.Biomedicines · 2023Review
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
aimSerotonin is crucial for proper foetal development, and the placenta has been described as a 'donor' of serotonin for the embryo/foetus. However, in later stages of gestation the foetus produces its own serotonin from maternally-derived tryptophan and placental supply is no longer needed. We propose a novel model of serotonin homeostasis in the term placenta with special focus on the protective role of organic cation transporter 3 (OCT3/SLC22A3).
methodsDually perfused rat term placenta was employed to quantify serotonin/tryptophan transport and metabolism. Placental membrane vesicles isolated from human term placenta were used to characterize serotonin transporters on both sides of the syncytiotrophoblast.
resultsWe obtained the first evidence that serotonin is massively taken up from the foetal circulation by OCT3. This uptake is concentration-dependent and inhibitable by OCT3 blockers of endogenous (glucocorticoids) or exogenous (pharmaceuticals) origin. Population analyses in rat placenta revealed that foetal sex influences placental extraction of serotonin from foetal circulation. Negligible foetal serotonin levels were detected in maternal-to-foetal serotonin/tryptophan transport and metabolic studies.
conclusionWe demonstrate that OCT3, localized on the foetus-facing membrane of syncytiotrophoblast, is an essential component of foeto-placental homeostasis of serotonin. Together with serotonin degrading enzyme, monoamine oxidase-A, this offers a protective mechanism against local vasoconstriction effects of serotonin in the placenta. However, this system may be compromised by OCT3 inhibitory molecules, such as glucocorticoids or antidepressants. Our findings open new avenues to explore previously unsuspected/unexplained complications during pregnancy including prenatal glucocorticoid excess and pharmacotherapeutic risks of treating pregnant women with OCT3 inhibitors.
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