The role of serotonin in prenatal ontogenesis

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Abstract

This review article summarizes current ideas about the role of serotonin in prenatal ontogenesis. We herein present the results of experimental and clinical studies that reveal the mechanisms of serotonin involvement in the establishment and development of the single “mother-placenta-fetus” system. The article highlights the key role of maternal serotonin in the genetic program for the morphological and functional development of fetal organs from the earliest stages of prenatal ontogenesis, in both normal and complicated pregnancy. We also discuss gestational factors that affect the production of maternal, placental, and fetal serotonin, as its deficiency or excess during pregnancy determines perinatal and long-term pathology programming in the offspring. The article substantiates the prospects for using serotonin as a biochemical marker of brain damage in a newborn for the timely application of neuroprotection and the prevention of adverse consequences.

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About the authors

Inna I. Evsyukova

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Author for correspondence.
Email: eevs@yandex.ru
ORCID iD: 0000-0003-4456-2198
SPIN-code: 4444-4567

MD, Dr. Sci. (Med.), Professor

Russian Federation, Saint Petersburg

References

  1. Bacqué-Cazenave J, Bharatiya R, Barrière G, et al. Serotonin in animal cognition and behavior. Int J Mol Sci. 2020;21(5). doi: 10.3390/ijms21051649
  2. Park S, Kim Y, Lee J, et al. A systems biology approach to investigating the interaction between serotonin synthesis by tryptophan hydroxylase and the metabolic homeostasis. Int J Mol Sci. 2021;22(5). doi: 10.3390/ijms22052452
  3. Wu H, Denna TH, Storkersen JN, Gerriets VA. Beyond a neurotransmitter: the role of serotonin in inflammation and immunity. Pharmacol Res. 2019;140:100–114. doi: 10.1016/j.phrs.2018.06.015
  4. Yabut JM, Crane JD, Green AE, et al. Emerging roles for serotonin in regulating metabolism: new implications for an ancient molecule. Endocr Rev. 2019;40(4):1092–1107. doi: 10.1210/er.2018-00283
  5. Liu N, Sun S, Wang P, et al. The mechanism of secretion and metabolism of gut-derived 5-hydroxytryptamine. Int J Mol Sci. 2021;22(15). doi: 10.3390/ijms22157931
  6. Eisinger F, Patzelt J, Langer HF. The platelet response to tissue injury. Front Med (Lausanne). 2018;5. doi: 10.3389/fmed.2018.00317
  7. Guzel T, Mirowska-Guzel D. The role of serotonin neurotransmission in gastrointestinal tract and pharmacotherapy. Molecules. 2022;27(5). doi: 10.3390/molecules27051680
  8. Shong KE, Oh CM, Namkung J, et al. Serotonin regulates de novo lipogenesis in adipose tissues through serotonin receptor 2A. Endocrinol Metab (Seoul). 2020;35(2):470–479. doi: 10.3803/EnM.2020.35.2.470
  9. Martin AM, Yabut JM, Choo JM, et al. The gut microbiome regulates host glucose homeostasis via peripheral serotonin. Proc Natl Acad Sci USA. 2019;116(40):19802–19804. doi: 10.1073/pnas.1909311116
  10. Berger M, Gray JA, Roth BL. The expanded biology of serotonin. Annu Rev Med. 2009;60:355–366. doi: 10.1146/annurev.med.60.042307.110802
  11. Fanibunda SE, Deb S, Maniyadath B, et al. Serotonin regulates mitochondrial biogenesis and function in rodent cortical neurons via the 5-HT2A receptor and SIRT1-PGC-1α axis. Proc Natl Acad Sci USA. 2019;116(22):11028–11037. doi: 10.1073/pnas.1821332116
  12. Azouzi S, Santuz H, Morandat S, et al. Antioxidant and membrane binding properties of serotonin protect lipids from oxidation. Biophys J. 2017;112(9):1863–1873. doi: 10.1016/j.bpj.2017.03.037
  13. Carrasco GA, Van de Kar LD. Neuroendocrine pharmacology of stress. Eur J Pharmacol. 2003;463(1–3):235–272. doi: 10.1016/s0014-2999(03)01285-8
  14. Kroeze WK, Kristiansen K, Roth BL. Molecular biology of serotonin receptors structure and function at the molecular level. Curr Top Med Chem. 2002;2(6):507–528. doi: 10.2174/1568026023393796
  15. Hodo TW, de Aquino MTP, Shimamoto A, et al. Critical neurotransmitters in the neuroimmune network. Front Immunol. 2020;11. doi: 10.3389/fimmu.2020.01869
  16. Shah R, Courtiol E, Castellanos FX, et al. Abnormal serotonin levels during perinatal development lead to behavioral deficits in adulthood. Front Behav Neurosci. 2018;12. doi: 10.3389/fnbeh.2018.00114
  17. Brummelte S, Mc Glanaghy E, Bonnin A, et al. Developmental changes in serotonin signaling: Implications for early brain function, behavior and adaptation. Neuroscience. 2017;342:212–231. doi: 10.1016/j.neuroscience.2016.02.037
  18. Kanova M, Kohout P. Tryptophan: a unique role in the critically Ill. Int J Mol Sci. 2021;22(21). doi: 10.3390/ijms222111714
  19. Badawy AA. Tryptophan metabolism, disposition and utilization in pregnancy. Biosci Rep. 2015;35(5). doi: 10.1042/BSR20150197
  20. Shallie PD, Naicker T. The placenta as a window to the brain: a review on the role of placental markers in prenatal programming of neurodevelopment. Int J Dev Neurosci. 2019;73:41–49. doi: 10.1016/j.ijdevneu.2019.01.003
  21. Laurent L, Deroy K, St-Pierre J, et al. Human placenta expresses both peripheral and neuronal isoform of tryptophan hydroxylase. Biochimie. 2017;140:159–165. doi: 10.1016/j.biochi.2017.07.008
  22. Viau M, Lafond J, Vaillancourt C. Expression of placental serotonin transporter and 5-HT 2A receptor in normal and gestational diabetes mellitus pregnancies. Reprod Biomed Online. 2009;19(2):207–215. doi: 10.1016/s1472-6483(10)60074-0
  23. Hadden C, Fahmi T, Cooper A, et al. Serotonin transporter protects the placental cells against apoptosis in caspase 3-independent pathway. J Cell Physiol. 2017;232(12):3520–3529. doi: 10.1002/jcp.25812
  24. Rosenfeld CS. Placental serotonin signaling, pregnancy outcomes, and regulation of fetal brain development. Biol Reprod. 2020;102(3):532–538. doi: 10.1093/biolre/ioz204
  25. Kliman HJ, Quaratella SB, Setaro AC, et al. Pathway of maternal serotonin to the human embryo and fetus. Endocrinology. 2018;159(4):1609–1629. doi: 10.1210/en.2017-03025
  26. Brenner B, Harney JT, Ahmed BA, et al. Plasma serotonin levels and the platelet serotonin transporter. J Neurochem. 2007;102(1):206–215. doi: 10.1111/j.1471-4159.2007.04542.x
  27. Baković P, Kesić M, Perić M, et al. Differential serotonin uptake mechanisms at the human maternal-fetal interface. Int J Mol Sci. 2021;22(15). doi: 10.3390/ijms22157807
  28. Forstner D, Guettler J, Gauster M. Changes in maternal platelet physiology during gestation and their interaction with trophoblasts. Int J Mol Sci. 2021;22(19). doi: 10.3390/ijms221910732
  29. Romero-Reyes J, Molina-Hernández A, Díaz NF, et al. Role of serotonin in vertebrate embryo development. Reprod Biol. 2021;21(1). doi: 10.1016/j.repbio.2020.100475
  30. Romero-Reyes J, Vázquez-Martínez ER, Bahena-Alvarez D, et al. Differential localization of serotoninergic system elements in human amniotic epithelial cells. Biol Reprod. 2021;105(2):439–448. doi: 10.1093/biolre/ioab106
  31. Xing L, Huttner WB. Neurotransmitters as modulators of neural progenitor cell proliferation during mammalian neocortex development. Front Cell Dev Biol. 2020;8.
  32. Ranzil S, Walker DW, Borg AJ, et al. The relationship between the placental serotonin pathway and fetal growth restriction. Biochimie. 2019;161:80–87. doi: 10.1016/j.biochi.2018.12.016
  33. Farrelly LA, Thompson RE, Zhao S, et al. Histone serotonylation is a permissive modification that enhances TFIID binding to H3K4me3. Nature. 2019;567(7749):535–539. doi: 10.1038/s41586-019-1024-7
  34. Murthy S, Niquille M, Hurni N, et al. Serotonin receptor 3A controls interneuron migration into the neocortex. Nat Commun. 2014;5. doi: 10.1038/ncomms6524
  35. Holst SC, Landolt H-P. Sleep-wake neurochemistry. Sleep Med Clin. 2022;17(2):151–160. doi: 10.1016/j.jsmc.2022.03.002
  36. Chen HL, Gao JX, Chen YN, et al. Rapid eye movement sleep during early life: a comprehensive narrative review. Int J Environ Res Public Health. 2022;19(20). doi: 10.3390/ijerph192013101
  37. Kolk SM, Rakic P. Development of prefrontal cortex. Neuropsychopharmacology. 2022;47(1):41–57. doi: 10.1038/s41386-021-01137-9
  38. Bonnin A, Levitt P. Fetal, maternal, and placental sources of serotonin and new implications for developmental programming of the brain. Neuroscience. 2011;197:1–7. doi: 10.1016/j.neuroscience.2011.10.005
  39. Gaspar P, Cases O, Maroteaux L. The developmental role of serotonin: news from mouse molecular genetics. Nat Rev Neurosci. 2003;4(12):1002–1012. doi: 10.1038/nrn1256
  40. Herlenius E, Lagercrantz H. Development of neurotransmitter systems during critical periods. Exp Neurol. 2004;190:S8–S21. doi: 10.1016/j.expneurol.2004.03.027
  41. Alhajeri MM, Alkhanjari RR, Hodeify R, et al. Neurotransmitters, neuropeptides and calcium in oocyte maturation and early development. Front Cell Dev Biol. 2022;10. doi: 10.3389/fcell.2022.980219
  42. Soslau G. Cardiovascular serotonergic system: evolution, receptors, transporter, and function. J Exp Zool A Ecol Integr Physiol. 2022;337(2):115–127. doi: 10.1002/jez.2554
  43. Launay JM. Sérotonine et système cardio-vasculaire: rôle du récepteur sérotoninergique 5-HT2B [Serotonin and the cardiovascular system: role of the serotoninergic 5-HT 2B receptor]. Bull Acad Natl Med. 2003;187(1):117–127. (In Fr.)
  44. Kent ME, Hu B, Eggleston TM, et al. Hypersensitivity of zebrafish htr2b mutant embryos to sertraline indicates a role for serotonin signaling in cardiac development. J Cardiovasc Pharmacol. 2022;80(2):261–269. doi: 10.1097/FJC.0000000000001297
  45. -HT2B receptors: from molecular biology to clinical applications. Ed. by L. Maroteaux, L. Monassier. New York: Springer; 2021. doi: 10.1007/978-3-030-55920-5
  46. Mel’nikova VI, Isvol’skaya MS, Voronova SN, et al. The role of serotonin in the immune system development and functioning during ontogenesis. Biology Bulletin (Izvestiya RAN. Seriya biologicheskaya). 2012;(3):237–243. (In Russ.)
  47. Sunday ME. Pulmonary Neuroendocrine cells and lung development. Endocr Pathol. 1996;7(3):173–201. doi: 10.1007/BF02739921
  48. Eenjes E, Tibboel D, Wijnen RMH, et al. Lung epithelium development and airway regeneration. Front Cell Dev Biol. 2022;10. doi: 10.3389/fcell.2022.1022457
  49. Nikolić J, Vukojević K, Šoljić V, et al. Expression patterns of serotonin receptors 5-HT1A, 5-HT2A, and 5-HT3A during human fetal lung development. Int J Mol Sci. 2023;24(3). doi: 10.3390/ijms24032965
  50. Castro EC, Sen P, Parks WT, et al. The role of serotonin transporter in human lung development and in neonatal lung disorders. Can Respir J. 2017;2017. doi: 10.1155/2017/9064046
  51. Cutz E, Yeger H, Pan J. Pulmonary neuroendocrine cell system in pediatric lung disease-recent advances. Pediatr Dev Pathol. 2007;10(6):419–435. doi: 10.2350/07-04-0267.1
  52. Garg A, Sui P, Verheyden JM, et al. Consider the lung as a sensory organ: a tip from pulmonary neuroendocrine cells. Curr Top Dev Biol. 2019;132:67–89. doi: 10.1016/bs.ctdb.2018.12.002
  53. Cummings KJ, Hodges MR. The serotonergic system and the control of breathing during development. Respir Physiol Neurobiol. 2019;270. doi: 10.1016/j.resp.2019.103255
  54. Penkova N, Penkov R, Hrischev P, et al. Immunohistochemical study on the expression of serotonin and 5HTR3 in gastrointestinal tract of rat embryos and newborns. J Bio Sci Biotech. 2012;53–56.
  55. Gershon MD. 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr Opin Endocrinol Diabetes Obes. 2013;20(1):14–21. doi: 10.1097/MED.0b013e32835bc703
  56. Indrio F, Neu J, Pettoello-Mantovani M, et al. Development of the gastrointestinal tract in newborns as a challenge for an appropriate nutrition: a narrative review. Nutrients. 2022;14(7). doi: 10.3390/nu14071405
  57. Erikci A, Ucar G, Yabanoglu-Ciftci S. Role of serotonin in the regulation of renal proximal tubular epithelial cells. Ren Fail. 2016;38(7):1141–1150. doi: 10.1080/0886022X.2016.1194165
  58. Hanswijk SI, Spoelder M, Shan L, et al. Gestational factors throughout fetal neurodevelopment: the serotonin link. Int J Mol Sci. 2020;21(16). doi: 10.3390/ijms21165850
  59. Kratimenos P, Penn AA. Placental programming of neuropsychiatric disease. Pediatr Res. 2019;86(2):157–164. doi: 10.1038/s41390-019-0405-9
  60. Huang X, Kuang S, Applegate TJ, et al. Prenatal serotonin fluctuation affects serotoninergic development and related neural circuits in chicken embryos. Neuroscience. 2021;473:66–80. doi: 10.1016/j.neuroscience.2021.08.011
  61. Abbott PW, Gumusoglu SB, Bittle J, et al. Prenatal stress and genetic risk: how prenatal stress interacts with genetics to alter risk for psychiatric illness. Psychoneuroendocrinology. 2018;90:9–21. doi: 10.1016/j.psyneuen.2018.01.019
  62. Anderson KN, Lind JN, Simeone RM, et al. Maternal use of specific antidepressant medications during early pregnancy and the risk of selected birth defects. JAMA Psychiatry. 2020;77(12):1246–1255. doi: 10.1001/jamapsychiatry.2020.2453
  63. Domingues RR, Fricke HP, Sheftel CM, et al. Effect of low and high doses of two selective serotonin reuptake inhibitors on pregnancy outcomes and neonatal mortality. Toxics. 2022;10(1). doi: 10.3390/toxics10010011
  64. Horackova H, Karahoda R, Cerveny L, et al. Effect of selected antidepressants on placental homeostasis of serotonin: maternal and fetal perspectives. Pharmaceutics. 2021;13(8). doi: 10.3390/pharmaceutics13081306
  65. Uguz F. Selective serotonin reuptake inhibitors and the risk of congenital anomalies: a systematic review of current meta-analyses. Expert Opin Drug Saf. 2020;19(12):1595–1604. doi: 10.1080/14740338.2020.1832080
  66. Domingues RR, Wiltbank MC, Hernandez LL. Pregnancy complications and neonatal mortality in a serotonin transporter null mouse model: insight into the use of selective serotonin reuptake inhibitor during pregnancy. Front Med (Lausanne). 2022;9. doi: 10.3389/fmed.2022.848581
  67. Sun M, Zhang S, Li Y, et al. Effect of maternal antidepressant use during the pre-pregnancy/early pregnancy period on congenital heart disease: a prospective cohort study in Central China. Front Cardiovasc Med. 2022;9. doi: 10.3389/fcvm.2022.916882
  68. Pei S, Liu L, Zhong Z, et al. Risk of prenatal depression and stress treatment: alteration on serotonin system of offspring through exposure to. Sci Rep. 2016;6. doi: 10.1038/srep33822
  69. da Silva Junior CA, Marques DA, Patrone LGA, et al. Intra-uterine diazepam exposure decreases the number of catecholaminergic and serotoninergic neurons of neonate rats. Neurosci Lett. 2023;795. doi: 10.1016/j.neulet.2022.137014
  70. Williams M, Zhang Z, Nance E, et al. Maternal inflammation results in altered tryptophan metabolism in rabbit placenta and fetal brain. Dev Neurosci. 2017;39(5):399–412. doi: 10.1159/000471509
  71. Huang X, Feng Z, Cheng H-W. Perspective: gestational tryptophan fluctuation altering neuroembryogenesis and psychosocial development. Cells. 2022;11(8). doi: 10.3390/cells11081270
  72. Vehmeijer FOL, Guxens M, Duijts L, et al. Maternal psychological distress during pregnancy and childhood health outcomes: a narrative review. J Dev Orig Health Dis. 2019;10(3):274–285. doi: 10.1017/S2040174418000557
  73. Rakers F, Rupprecht S, Dreiling M, et al. Transfer of maternal psychosocial stress to the fetus. Neurosci Biobehav Rev. 2017. doi: 10.1016/j.neubiorev.2017.02.019
  74. St-Pierre J, Laurent L, King S, et al. Effects of prenatal maternal stress on serotonin and fetal development. Placenta. 2016;48:S66–S71. doi: 10.1016/j.placenta.2015.11.013
  75. Van den Bergh BRH, van den Heuvel MI, Lahti M, et al. Prenatal developmental origins of behavior and mental health: The influence of maternal stress in pregnancy. Neurosci Biobehav Rev. 2020;117:26–64. doi: 10.1016/j.neubiorev.2017.07.003
  76. Zvereva NA, Milyutina YP, Arutjunyan AV, et al. Serotonin and cyclic sleep organization in full-term newborn infants with intrauterine growth retardation. Journal of Obstetrics and Women’s Diseases. 2023;71(6):5–14. (In Russ.) doi: 10.17816/JOWD112611

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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 66759 от 08.08.2016 г. 
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия Эл № 77 - 6389 от 15.07.2002 г.


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