Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 8

The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.

Perfused rat term placenta as a preclinical model to investigate placental dopamine and norepinephrine transport

Horackova, Hana, Vachalova, Veronika, Abad, Cilia, Karahoda, Rona, Staud, Frantisek·2023·Clinical Science
DOI 10.1042/cs20220726
Open this paper in CoChat — free account

Abstract

The placenta represents a non-neuronal organ capable of transporting and metabolizing monoamines. Since these bioactive molecules participate in numerous processes essential for placental and fetal physiology, any imbalance in their levels during pregnancy may affect brain development, projecting a higher risk of behavioral disorders in childhood or adulthood. Notably, the monoamine system in the placenta is a target of various psychoactive drugs and can be disrupted in several pregnancy pathologies. As research in pregnant women poses significant ethical restrictions, animal models are widely employed to study monoamine homeostasis as a mechanism involved in fetal programming. However, detailed knowledge of monoamine transport in the rat placenta is still lacking. Moreover, relatability to the human placental monoamine system is not examined. The present study provides insights into the transplacental monoamine dynamics between maternal and fetal circulation. We show that norepinephrine maternal-to-fetal transport is <4% due to high metabolism within the trophoblast. In contrast, dopamine maternal-to-fetal transport exceeds 25%, likely through passive transport across the membrane. In addition, we show high clearance of norepinephrine and dopamine from the fetal circulation mediated by the organic cation transporter 3 (OCT3). Altogether, we present transcriptional and functional evidence that the in situ rat placenta perfusion represents a suitable model for (patho)physiological investigation of dopamine and norepinephrine homeostasis in the fetoplacental unit. With the rapid advancements in drug discovery and environmental toxicity, the use of rat placenta as a preclinical model could facilitate screening of possible xenobiotic effects on monoamine homeostasis in the placenta.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1042/cs20220726

Cites

5 of 5 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Research works printed but not linked: 57

  1. Thomas, 1995, Noradrenaline is essential for mouse fetal development, Nature, 374, 643, 10.1038/374643a0 · DOI · Paper page
  2. Padbury, 1989, Functional maturation of the adrenal medulla and peripheral sympathetic nervous system, Baillieres Clin. Endocrinol. Metab., 3, 689, 10.1016/S0950-351X(89)80049-7 · DOI
  3. Lee, 1999, Effects of dopamine and melatonin on the regulation of the PIT-1 isotype, placental growth hormone and lactogen gene expressions in the rat placenta, Mol. Cells, 9, 646, 10.1016/S1016-8478(23)13597-7 · DOI
  4. Yarlagadda, 2019, Placental barrier and autism spectrum disorders: the roles of prolactin and dopamine in the developing fetal brain-part II, Innov. Clin. Neurosci., 16, 36
  5. Previc, 2007, Prenatal influences on brain dopamine and their relevance to the rising incidence of autism, Med. Hypotheses, 68, 46, 10.1016/j.mehy.2006.06.041 · DOI
  6. Robinson, 2001, Genetically determined low maternal serum dopamine beta-hydroxylase levels and the etiology of autism spectrum disorders, Am. J. Med. Genet., 100, 30, 10.1002/ajmg.1187 · DOI
  7. Rosenfeld, 2021, The placenta-brain-axis, J. Neurosci. Res., 99, 271, 10.1002/jnr.24603 · DOI · Paper page
  8. Ramamoorthy, 1993, Expression of a cocaine-sensitive norepinephrine transporter in the human placental syncytiotrophoblast, Biochemistry, 32, 1346, 10.1021/bi00056a021 · DOI
  9. Ramamoorthy, 1992, Active transport of dopamine in human placental brush-border membrane vesicles, Am. J. Physiol., 262, C1189, 10.1152/ajpcell.1992.262.5.C1189 · DOI
  10. Ganapathy, 1993, Transport and metabolism of monoamines in the human placenta: a review, Placenta, 14, 35, 10.1016/S0143-4004(05)80281-4 · DOI
  11. Sata, 2005, Functional analysis of organic cation transporter 3 expressed in human placenta, J. Pharmacol. Exp. Ther., 315, 888, 10.1124/jpet.105.086827 · DOI
  12. Karahoda, 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, Acta Physiol. (Oxf.), 229, e13478, 10.1111/apha.13478 · DOI
  13. Horackova, 2022, Functional characterization of dopamine and norepinephrine transport across the apical and basal plasma membranes of the human placental syncytiotrophoblast, Sci. Rep., 12, 11603, 10.1038/s41598-022-15790-7 · DOI · Paper page
  14. Egashira, 1976, Studies on monoamine oxidase. XVIII. Enzymic properties of placental monoamine oxidase, Jpn. J. Pharmacol., 26, 493, 10.1254/jjp.26.493 · DOI
  15. Castrén, 1974, The simultaneous function of catechol-O-methyltransferase and monoamine oxidase in human placenta, Acta Obstet. Gynecol. Scand., 53, 41, 10.3109/00016347409156887 · DOI
  16. Horackova, 2021, Effect of selected antidepressants on placental homeostasis of serotonin: maternal and fetal perspectives, Pharmaceutics, 13, 10.3390/pharmaceutics13081306 · DOI
  17. Karahoda, 2021, Prenatal inflammation as a link between placental expression signature of tryptophan metabolism and preterm birth, Hum. Mol. Genet., 30, 2053, 10.1093/hmg/ddab169 · DOI
  18. Ranzil, 2019, Disrupted placental serotonin synthetic pathway and increased placental serotonin: Potential implications in the pathogenesis of human fetal growth restriction, Placenta, 84, 74, 10.1016/j.placenta.2019.05.012 · DOI
  19. Sivasubramaniam, 2002, Monoamine oxidase expression and activity in human placentae from pre-eclamptic and normotensive pregnancies, Placenta, 23, 163, 10.1053/plac.2001.0770 · DOI
  20. McKiever, 2020, Challenges in conducting clinical research studies in pregnant women, J. Pharmacokinet. Pharmacodyn., 47, 287, 10.1007/s10928-020-09687-z · DOI
  21. Vachalova, 2022, Functional reorganization of monoamine transport systems during villous trophoblast differentiation: evidence of distinct differences between primary human trophoblasts and BeWo cells, Reprod. Biol. Endocrinol., 20, 112, 10.1186/s12958-022-00981-8 · DOI · Paper page
  22. Wilson, 2011, Focus on: the use of animal models for the study of fetal alcohol spectrum disorders, Alcohol. Res. Health., 34, 92
  23. Furukawa, 2019, Morphology and physiology of rat placenta for toxicological evaluation, J. Toxicol. Pathol., 32, 1, 10.1293/tox.2018-0042 · DOI
  24. Boyd, 1975, The Human Placenta
  25. Sun, 2019, Trend of antidepressants before, during, and after pregnancy across two decades-a population-based study, Brain Behav., 9, e01441, 10.1002/brb3.1441 · DOI
  26. Bourke, 2013, Prenatal exposure to escitalopram and/or stress in rats: a prenatal stress model of maternal depression and its treatment, Psychopharmacology (Berl.), 228, 231, 10.1007/s00213-013-3030-z · DOI
  27. Wang, 2017, The recent progress in animal models of depression, Prog. Neuropsychopharmacol. Biol. Psychiatry, 77, 99, 10.1016/j.pnpbp.2017.04.008 · DOI · Paper page
  28. Houwing, 2020, Perinatal fluoxetine treatment and dams' early life stress history alter affective behavior in rat offspring depending on serotonin transporter genotype and sex, Behav. Brain Res., 392, 112657, 10.1016/j.bbr.2020.112657 · DOI
  29. Olivier, 2011, Fluoxetine administration to pregnant rats increases anxiety-related behavior in the offspring, Psychopharmacology (Berl.), 217, 419, 10.1007/s00213-011-2299-z · DOI
  30. Ellenbroek, 2016, Rodent models in neuroscience research: is it a rat race?, Dis. Model Mech., 9, 1079, 10.1242/dmm.026120 · DOI · Paper page
  31. Soares, 1987, Establishment of a rat placental cell line expressing characteristics of extraembryonic membranes, Dev. Biol., 124, 134, 10.1016/0012-1606(87)90466-0 · DOI
  32. Shi, 1997, Permeability and metabolic properties of a trophoblast cell line (HRP-1) derived from normal rat placenta, Exp. Cell. Res., 234, 147, 10.1006/excr.1997.3603 · DOI
  33. Van Loon, 1980, Plasma dopamine: source, regulation, and significance, Metabolism, 29, 1119, 10.1016/0026-0495(80)90020-7 · DOI
  34. Newnham, 1984, Fetal catecholamine release with preterm delivery, Am. J. Obstet. Gynecol., 149, 888, 10.1016/0002-9378(84)90610-0 · DOI
  35. Zhou, 2004, Norepinephrine transporter inhibitors and their therapeutic potential, Drugs Future, 29, 1235, 10.1358/dof.2004.029.12.855246 · DOI
  36. Berger, 1990, Interaction of [3H]GBR 12935 and GBR 12909 with the dopamine uptake complex in nucleus accumbens, Eur. J. Pharmacol., 177, 91, 10.1016/0014-2999(90)90554-J · DOI
  37. Koepsell, 2020, Organic cation transporters in health and disease, Pharmacol. Rev., 72, 253, 10.1124/pr.118.015578 · DOI
  38. Horton, 2013, Decynium-22 enhances SSRI-induced antidepressant-like effects in mice: uncovering novel targets to treat depression, J. Neurosci., 33, 10534, 10.1523/JNEUROSCI.5687-11.2013 · DOI
  39. Staud, 2006, Expression and transport activity of breast cancer resistance protein (Bcrp/Abcg2) in dually perfused rat placenta and HRP-1 cell line, J. Pharmacol. Exp. Ther., 319, 53, 10.1124/jpet.106.105023 · DOI
  40. Ahmadimoghaddam, 2013, Transfer of metformin across the rat placenta is mediated by organic cation transporter 3 (OCT3/SLC22A3) and multidrug and toxin extrusion 1 (MATE1/SLC47A1) protein, Reprod. Toxicol., 39, 17, 10.1016/j.reprotox.2013.03.001 · DOI
  41. Baker, 1992, Insights into the mechanisms of action of the MAO inhibitors phenelzine and tranylcypromine: a review, J. Psychiatry Neurosci., 17, 206
  42. Gordin, 2004, Clinical advantages of COMT inhibition with entacapone - a review, J. Neural. Transm. (Vienna), 111, 1343, 10.1007/s00702-004-0190-3 · DOI
  43. Sodha, 1984, Transfer and metabolism of norepinephrine studied from maternal-to-fetal and fetal-to-maternal sides in the in vitro perfused human placental lobe, Am. J. Obstet. Gynecol., 148, 474, 10.1016/0002-9378(84)90729-4 · DOI · Paper page
  44. Watanabe, 1990, Placental and blood-brain barrier transfer following prenatal and postnatal exposures to neuroactive drugs: relationship with partition coefficient and behavioral teratogenesis, Toxicol. Appl. Pharmacol., 105, 66, 10.1016/0041-008X(90)90359-3 · DOI
  45. Soares-da-Silva, 1997, Uptake of L-3,4-dihydroxyphenylalanine and dopamine formation in cultured renal epithelial cells, Biochem. Pharmacol., 54, 1037, 10.1016/S0006-2952(97)00318-3 · DOI
  46. Scholze, 2001, Substantial loss of substrate by diffusion during uptake in HEK-293 cells expressing neurotransmitter transporters, Neurosci. Lett., 309, 173, 10.1016/S0304-3940(01)02058-4 · DOI
  47. Ingebretsen, 1979, Active and passive transport of dopamine in chromaffin granule ghosts isolated from bovine adrenal medulla, J. Biol. Chem., 254, 3833, 10.1016/S0021-9258(18)50662-1 · DOI
  48. Ben-Jonathan, 2020, Dopamine: Endocrine and Oncogenic Functions, 10.1201/9780429402272 · DOI
  49. Abad, 2020, Profiling of tryptophan metabolic pathways in the rat fetoplacental unit during gestation, Int. J. Mol. Sci., 21, 10.3390/ijms21207578 · DOI
  50. Iqbal, 2021, Catechol-O-methyltransferase and pregnancy outcome: an appraisal in rat, Reprod. Sci., 28, 462, 10.1007/s43032-020-00348-7 · DOI
  51. Bzoskie, 1995, Placental norepinephrine clearance: in vivo measurement and physiological role, Am. J. Physiol., 269, E145, 10.1152/ajpendo.1995.269.1.E145 · DOI
  52. Bzoskie, 1997, The contribution of transporter-dependent uptake to fetal catecholamine clearance, Biol. Neonate, 71, 102, 10.1159/000244403 · DOI
  53. Costa, 1988, Adrenocorticotropic hormone and catecholamines in maternal, umbilical and neonatal plasma in relation to vaginal delivery, J. Endocrinol. Invest., 11, 703, 10.1007/BF03350923 · DOI
  54. Jayanthi, 2002, Characterization of cocaine and antidepressant-sensitive norepinephrine transporters in rat placental trophoblasts, Br. J. Pharmacol., 135, 1927, 10.1038/sj.bjp.0704658 · DOI
  55. Karahoda, 2022, Trophoblast differentiation affects crucial nutritive functions of placental membrane transporters, Front. Cell Dev. Biol., 10, 820286, 10.3389/fcell.2022.820286 · DOI
  56. Karahoda, 2020, Dynamics of tryptophan metabolic pathways in human placenta and placental-derived cells: effect of gestation age and trophoblast differentiation, Front. Cell Dev. Biol., 8, 574034, 10.3389/fcell.2020.574034 · DOI
  57. Karttunen, 2015, Criteria and challenges of the human placental perfusion – data from a large series of perfusions, Toxicol. in Vitro, 29, 1482, 10.1016/j.tiv.2015.06.001 · DOI

Metadata

Authors
Horackova, H., Vachalova, V., Abad, C., Karahoda, R., & Staud, F.
Venue
Clinical Science
Publisher
Portland Press Ltd.
Published
2023-01
Volume
137
Issue
2
Pages
149-161
ISSN
  • 0143-5221
  • 1470-8736
DOI
10.1042/cs20220726
Cited by
8
References
5
Language
en
Licence
creativecommons.org/licenses/by/2.0/ (vor, 3 d)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.