{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:37Z","timestamp":1787028577451,"version":"build-2736575974"},"reference-count":98,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["1R03HD114968-01A1"],"award-info":[{"award-number":["1R03HD114968-01A1"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015509","name":"Missouri Department of Health and Senior Services","doi-asserted-by":"publisher","award":["AOC23380006"],"award-info":[{"award-number":["AOC23380006"]}],"id":[{"id":"10.13039\/100015509","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Serotonin reuptake inhibitors (SSRIs) are commonly prescribed to pregnant women experiencing depression. Such drugs, however, might adversely affect placenta and fetal brain development. Parietal trophoblast giant cells (pTGCs) in the mouse placenta are postulated to internalize maternal serotonin (5-HT) via transport through SERT, encoded by Slc6a4, and to provide the initial source of 5-HT to the emerging brain via the placental\u2013brain axis. Genetic deletion of Slc6a4 in pTGCs has been hypothesized to impact placental and fetal brain development. A transgenic mouse line with high-affinity SERT, encoded by Slc6a4, was selectively deleted by pairing mice with Cre recombinase linked to Prl2c2, with LoxP sites flanking the Slc6a4 gene. PRL2C2 is solely expressed by pTGCs and other giant cells of the placenta. To compare placental and fetal brain development in selective Slc6a4 KO and WT mice, 5-HT content in the placenta and fetal brains of conceptuses was measured. No significant differences in 5-HT content were evident between knockout (KO) and wild-type (WT) placentas or fetal brains. However, there were significantly fewer pTGCs in KO placentas compared to WT (p \u2264 0.05). Sexually dimorphic differences in gene expression were evident in the placenta and fetal brain between KO and WT counterparts, with female conceptuses showing the most dramatic responses, including decrease in Prl7a2, Prl5a1, Prl3a1, Slc28a3, and Ceacam 15 in female placental samples. These findings suggest that ablation of Slc6a4 in pTGC disrupts the placenta\u2013brain axis in a sex-dependent manner. The results might have important clinical ramifications for pregnant women being treated with SSRIs.<\/jats:p>","DOI":"10.3390\/ijms27010436","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T16:08:00Z","timestamp":1767197280000},"page":"436","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Disruption of the Placenta\u2013Brain Axis in Transgenic Mice Lacking Serotonin Transporter (SERT) in Trophoblast Cells"],"prefix":"10.3390","volume":"27","author":[{"given":"David T.","family":"Ellenberger","sequence":"first","affiliation":[{"name":"Department of Pathobiology and Integrative Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Lyu","sequence":"additional","affiliation":[{"name":"Christopher S. Bond Life Science Center, University of Missouri, Columbia, MO 65211, USA"},{"name":"Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25703, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalind T. B.","family":"Herrington","sequence":"additional","affiliation":[{"name":"Department of Pathobiology and Integrative Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA"},{"name":"Department of Biological Sciences, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica A.","family":"Kinkade","sequence":"additional","affiliation":[{"name":"Veterinary Diagnostic Laboratory, University of Missouri, Columbia, MO 65201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo W.","family":"Leone","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Ying","family":"Sze","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan J.","family":"Bivens","sequence":"additional","affiliation":[{"name":"Genomics Technology Core Facility, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2392-6338","authenticated-orcid":false,"given":"R. 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Edwards School of Medicine, Marshall University, Huntington, WV 25703, USA"},{"name":"Department of Biomedical Informatics, Biostatistics, and Medical Epidemiology, School of Medicine, University of Missouri, Columbia, MO 65201, USA"},{"name":"MU Institute for Data Science and Informatics, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4137-3933","authenticated-orcid":false,"given":"Cheryl S.","family":"Rosenfeld","sequence":"additional","affiliation":[{"name":"Department of Pathobiology and Integrative Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA"},{"name":"MU Institute for Data Science and Informatics, University of Missouri, Columbia, MO 65211, USA"},{"name":"Department of Genetics Area Program, University of Missouri, Columbia, MO 65211, USA"},{"name":"Department of Thompson Center for Autism and Neurobehavioral Disorders, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S2215-0366(16)30284-X","article-title":"Epidemiology of maternal depression, risk factors, and child outcomes in low-income and middle-income countries","volume":"3","author":"Gelaye","year":"2016","journal-title":"Lancet Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1136\/bmj.323.7307.257","article-title":"Cohort study of depressed mood during pregnancy and after childbirth","volume":"323","author":"Evans","year":"2001","journal-title":"BMJ"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1001\/archgenpsychiatry.2010.111","article-title":"A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction","volume":"67","author":"Grote","year":"2010","journal-title":"Arch. 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