{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T12:41:38Z","timestamp":1780490498340,"version":"3.54.1"},"reference-count":40,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["23-24-00352"],"award-info":[{"award-number":["23-24-00352"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Placental serotonin is recognized as a key component of feto-placental physiology and can be influenced by environmental factors such as maternal diet, drugs, stress, and immune activation. In this study, we compared the contribution of placental and fetal sources to the maintenance of serotonin levels required for normal fetal development during ontogenetic dynamics. Our results demonstrated the leading role of the placenta at almost all stages of development. We investigated the modulatory effect of inflammation on placental serotonin levels. The data obtained showed that the susceptibility to prenatal inflammation depends on its severity and varies considerably at different stages of development. According to our results, inflammation-induced modulation of placental serotonin levels can be prevented by immunoglobulin administration at both early and late stages of development. Disturbances in placental serotonin signaling during critical developmental periods may have long-lasting consequences for the health and behavior of the offspring. Therefore, the ability to prevent environmental modulation of placental serotonin, and hence negative effects on the developing fetus, is of great importance.<\/jats:p>","DOI":"10.3390\/ijms252413532","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T03:40:56Z","timestamp":1734493256000},"page":"13532","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Placenta as the Main Source of Serotonin in Ontogenetic Dynamics: Inflammation-Induced Modulation of Placental Serotonin Can Be Prevented by Immunoglobulin Administration"],"prefix":"10.3390","volume":"25","author":[{"given":"Nadezhda","family":"Bondarenko","sequence":"first","affiliation":[{"name":"Laboratory of Comparative Developmental Physiology, Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadezhda","family":"Lifantseva","sequence":"additional","affiliation":[{"name":"Laboratory of Comparative Developmental Physiology, Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Voronova","sequence":"additional","affiliation":[{"name":"Laboratory of Comparative Developmental Physiology, Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Melnikova","sequence":"additional","affiliation":[{"name":"Laboratory of Comparative Developmental Physiology, Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/35080570","article-title":"Placental Development: Lessons from Mouse Mutants","volume":"2","author":"Rossant","year":"2001","journal-title":"Nat. Rev. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.rbmo.2012.03.017","article-title":"Placental Adaptations to the Maternal\u2013Fetal Environment: Implications for Fetal Growth and Developmental Programming","volume":"25","author":"Sandovici","year":"2012","journal-title":"Reprod. BioMed. Online"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nature09972","article-title":"A Transient Placental Source of Serotonin for the Fetal Forebrain","volume":"472","author":"Bonnin","year":"2011","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Peri\u0107, M., Be\u010deheli, I., \u010ci\u010din-\u0160ain, L., Desoye, G., and \u0160tefulj, J. (2022). Serotonin System in the Human Placenta\u2014The Knowns and Unknowns. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1061317"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1242\/dev.124.9.1745","article-title":"5-HT2B Receptor-Mediated Serotonin Morphogenetic Functions in Mouse Cranial Neural Crest and Myocardiac Cells","volume":"124","author":"Choi","year":"1997","journal-title":"Development"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/S0736-5748(00)00032-0","article-title":"Expression of 5-HT2A, 5-HT2B and 5-HT2C Receptors in the Mouse Embryo","volume":"18","author":"Lauder","year":"2000","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0361-9230(01)00614-1","article-title":"Modern Views on an Ancient Chemical: Serotonin Effects on Cell Proliferation, Maturation, and Apoptosis","volume":"56","author":"Azmitia","year":"2001","journal-title":"Brain Res. Bull."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s004410100408","article-title":"Serotonin and Serotonin-like Substances as Regulators of Early Embryogenesis and Morphogenesis","volume":"305","author":"Buznikov","year":"2001","journal-title":"Cell Tissue Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1016\/S0960-9822(02)01199-5","article-title":"Serotonin Promotes Go-Dependent Neuronal Migration in Caenorhabditis Elegans","volume":"12","author":"Kindt","year":"2002","journal-title":"Curr. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/sj.npp.1300320","article-title":"Serotonin-Induced Increases in Adult Cell Proliferation and Neurogenesis Are Mediated Through Different and Common 5-HT Receptor Subtypes in the Dentate Gyrus and the Subventricular Zone","volume":"29","author":"Banasr","year":"2004","journal-title":"Neuropsychopharmacology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/nn1896","article-title":"Serotonin Modulates the Response of Embryonic Thalamocortical Axons to Netrin-1","volume":"10","author":"Bonnin","year":"2007","journal-title":"Nat. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1073\/pnas.0606722104","article-title":"Maternal Serotonin Is Crucial for Murine Embryonic Development","volume":"104","author":"Fligny","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/npp.2011.194","article-title":"Placental Source for 5-HT That Tunes Fetal Brain Development","volume":"37","author":"Bonnin","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"ref_14","first-page":"295","article-title":"Monoamines as Adaptive Developmental Regulators: Phenomenon and Mechanisms of Action","volume":"71","author":"Voronezhskaya","year":"2021","journal-title":"Neurosci. Behav. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2901","DOI":"10.1038\/s41467-022-30438-w","article-title":"Serotonin Limits Generation of Chromaffin Cells during Adrenal Organ Development","volume":"13","author":"Kameneva","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1134\/S160767292202003X","article-title":"Prenatal Stress and Adaptive Behavior of Offspring: The Role of Placental Serotonin","volume":"503","author":"Bondarenko","year":"2022","journal-title":"Dokl. Biochem. Biophys."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6041","DOI":"10.1523\/JNEUROSCI.2534-15.2016","article-title":"Maternal Inflammation Disrupts Fetal Neurodevelopment via Increased Placental Output of Serotonin to the Fetal Brain","volume":"36","author":"Goeden","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1093\/hmg\/ddab169","article-title":"Prenatal Inflammation as a Link between Placental Expression Signature of Tryptophan Metabolism and Preterm Birth","volume":"30","author":"Karahoda","year":"2021","journal-title":"Human Mol. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0959-4388(02)00299-4","article-title":"Maternal Infection: Window on Neuroimmune Interactions in Fetal Brain Development and Mental Illness","volume":"12","author":"Patterson","year":"2002","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.bbr.2008.12.016","article-title":"Immune Involvement in Schizophrenia and Autism: Etiology, Pathology and Animal Models","volume":"204","author":"Patterson","year":"2009","journal-title":"Behav. Brain Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuroscience.2011.10.005","article-title":"Fetal, Maternal, and Placental Sources of Serotonin and New Implications for Developmental Programming of the Brain","volume":"197","author":"Bonnin","year":"2011","journal-title":"Neuroscience"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1056\/NEJMra993360","article-title":"Immunomodulation of Autoimmune and Inflammatory Diseases with Intravenous Immune Globulin","volume":"345","author":"Kazatchkine","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1365-2249.2009.04022.x","article-title":"Intravenous Immunoglobulins\u2014Understanding Properties and Mechanisms","volume":"158","author":"Durandy","year":"2009","journal-title":"Clin. Exp. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.jaci.2010.10.030","article-title":"The IgG Molecule as a Biological Immune Response Modifier: Mechanisms of Action of Intravenous Immune Serum Globulin in Autoimmune and Inflammatory Disorders","volume":"127","author":"Ballow","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"41","DOI":"10.4049\/jimmunol.1701093","article-title":"IVIg Promote Cross-Tolerance against Inflammatory Stimuli In Vitro and In Vivo","volume":"201","author":"Cuevas","year":"2018","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1097\/SHK.0000000000000937","article-title":"Protection Against Lipopolysaccharide-Induced Immunosuppression by IgG and IgM","volume":"49","author":"Kyvelidou","year":"2018","journal-title":"Shock"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Abad, C., Karahoda, R., Kastner, P., Portillo, R., Horackova, H., Kucera, R., Nachtigal, P., and Staud, F. (2020). Profiling of Tryptophan Metabolic Pathways in the Rat Fetoplacental Unit during Gestation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207578"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1002\/cne.902850208","article-title":"Time Course of Expression of Neuropeptide Y, Calcitonin Gene-related Peptide, and NADPH Diaphorase Activity in Neurons of the Developing Murine Bowel and the Appearance of 5-hydroxytryptamine in Mucosal Enterochromaffin Cells","volume":"285","author":"Branchek","year":"1989","journal-title":"J. Comp. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/nprot.2012.144","article-title":"Ex Vivo Perfusion of Mid-to-Late-Gestation Mouse Placenta for Maternal-Fetal Interaction Studies during Pregnancy","volume":"8","author":"Goeden","year":"2013","journal-title":"Nat. Protoc."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Velasquez, J.C., Goeden, N., and Bonnin, A. (2013). Placental Serotonin: Implications for the Developmental Effects of SSRIs and Maternal Depression. Front. Cell. Neurosci., 7.","DOI":"10.3389\/fncel.2013.00047"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/s41398-020-00876-5","article-title":"Prenatal Stress Causes Intrauterine Inflammation and Serotonergic Dysfunction, and Long-Term Behavioral Deficits through Microbe- and CCL2-Dependent Mechanisms","volume":"10","author":"Chen","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/rmb2.12078","article-title":"Immune Modulation of i.v. Immunoglobulin in Women with Reproductive Failure","volume":"17","author":"Han","year":"2018","journal-title":"Reprod. Med. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hanswijk, S.I., Spoelder, M., Shan, L., Verheij, M.M.M., Muilwijk, O.G., Li, W., Liu, C., Kolk, S.M., and Homberg, J.R. (2020). Gestational Factors throughout Fetal Neurodevelopment: The Serotonin Link. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165850"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1002\/jnr.10423","article-title":"Effects of Intrauterine Inflammation on Developing Rat Brain","volume":"70","author":"Bell","year":"2002","journal-title":"J. Neurosci. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.clp.2008.07.011","article-title":"Cytokines and Perinatal Brain Damage","volume":"35","author":"Dammann","year":"2008","journal-title":"Clin. Perinatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.4049\/jimmunol.0903349","article-title":"IL-1 Receptor Antagonist Protects against Placental and Neurodevelopmental Defects Induced by Maternal Inflammation","volume":"184","author":"Girard","year":"2010","journal-title":"J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Sawa, T., Kinoshita, M., Inoue, K., Ohara, J., and Moriyama, K. (2019). Immunoglobulin for Treating Bacterial Infections: One More Mechanism of Action. Antibodies, 8.","DOI":"10.20944\/preprints201909.0144.v1"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1056\/NEJMra1009433","article-title":"Intravenous Immune Globulin in Autoimmune and Inflammatory Diseases","volume":"367","author":"Gelfand","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.ijdevneu.2011.02.011","article-title":"Intrauterine Inflammation, Insufficient to Induce Parturition, Still Evokes Fetal and Neonatal Brain Injury","volume":"29","author":"Elovitz","year":"2011","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1134\/S1607672917060151","article-title":"Expression of Components of the Serotonergic System in the Developing Rat Thymus","volume":"477","author":"Lifantseva","year":"2017","journal-title":"Dokl. Biochem. Biophys."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/24\/13532\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:54:17Z","timestamp":1760115257000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/24\/13532"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,18]]},"references-count":40,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["ijms252413532"],"URL":"https:\/\/doi.org\/10.3390\/ijms252413532","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,18]]}}}