{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:06:34Z","timestamp":1790787994000,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:00:00Z","timestamp":1693353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Normandy University","award":["UMR1245"],"award-info":[{"award-number":["UMR1245"]}]},{"name":"Normandy University","award":["UMR1245"],"award-info":[{"award-number":["UMR1245"]}]},{"name":"Normandy University","award":["UMR-S U1237"],"award-info":[{"award-number":["UMR-S U1237"]}]},{"name":"Normandy University","award":["00079259"],"award-info":[{"award-number":["00079259"]}]},{"name":"Rouen University, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","award":["UMR1245"],"award-info":[{"award-number":["UMR1245"]}]},{"name":"Rouen University, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","award":["UMR1245"],"award-info":[{"award-number":["UMR1245"]}]},{"name":"Rouen University, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","award":["UMR-S U1237"],"award-info":[{"award-number":["UMR-S U1237"]}]},{"name":"Rouen University, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","award":["00079259"],"award-info":[{"award-number":["00079259"]}]},{"name":"Rouen University Hospital, Fondation de France","award":["UMR1245"],"award-info":[{"award-number":["UMR1245"]}]},{"name":"Rouen University Hospital, Fondation de France","award":["UMR1245"],"award-info":[{"award-number":["UMR1245"]}]},{"name":"Rouen University Hospital, Fondation de France","award":["UMR-S U1237"],"award-info":[{"award-number":["UMR-S U1237"]}]},{"name":"Rouen University Hospital, Fondation de France","award":["00079259"],"award-info":[{"award-number":["00079259"]}]},{"name":"Rouen University","award":["UMR1245"],"award-info":[{"award-number":["UMR1245"]}]},{"name":"Rouen University","award":["UMR1245"],"award-info":[{"award-number":["UMR1245"]}]},{"name":"Rouen University","award":["UMR-S U1237"],"award-info":[{"award-number":["UMR-S U1237"]}]},{"name":"Rouen University","award":["00079259"],"award-info":[{"award-number":["00079259"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although alcohol consumption during pregnancy is a major cause of behavioral and learning disabilities, most FASD infants are late- or even misdiagnosed due to clinician\u2019s difficulties achieving early detection of alcohol-induced neurodevelopmental impairments. Neuroplacentology has emerged as a new field of research focusing on the role of the placenta in fetal brain development. Several studies have reported that prenatal alcohol exposure (PAE) dysregulates a functional placenta\u2013cortex axis, which is involved in the control of angiogenesis and leads to neurovascular-related defects. However, these studies were focused on PlGF, a pro-angiogenic factor. The aim of the present study is to provide the first transcriptomic \u201cplacenta\u2013cortex\u201d signature of the effects of PAE on fetal angiogenesis. Whole mouse genome microarrays of paired placentas and cortices were performed to establish the transcriptomic inter-organ \u201cplacenta\u2013cortex\u201d signature in control and PAE groups at gestational day 20. Genespring comparison of the control and PAE signatures revealed that 895 and 1501 genes were only detected in one of two placenta\u2013cortex expression profiles, respectively. Gene ontology analysis indicated that 107 of these genes were associated with vascular development, and String protein\u2013protein interaction analysis showed that they were associated with three functional clusters. PANTHER functional classification analysis indicated that \u201cintercellular communication\u201d was a significantly enriched biological process, and 27 genes were encoded for neuroactive ligand\/receptors interactors. Protein validation experiments involving Western blot for one ligand\u2013receptor couple (Agt\/AGTR1\/2) confirmed the transcriptomic data, and Pearson statistical analysis of paired placentas and fetal cortices revealed a negative correlation between placental Atg and cortical AGTR1, which was significantly impacted by PAE. In humans, a comparison of a 38WG control placenta with a 36WG alcohol-exposed placenta revealed low Agt immunolabeling in the syncytiotrophoblast layer of the alcohol case. In conclusion, this study establishes the first transcriptomic placenta\u2013cortex signature of a developing mouse. The data show that PAE markedly unbalances this inter-organ signature; in particular, several ligands and\/or receptors involved in the control of angiogenesis. These data support that PAE modifies the existing communication between the two organs and opens new research avenues regarding the impact of placental dysfunction on the neurovascular development of fetuses. Such a signature would present a clinical value for early diagnosis of brain defects in FASD.<\/jats:p>","DOI":"10.3390\/ijms241713484","type":"journal-article","created":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T09:14:41Z","timestamp":1693473281000},"page":"13484","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Prenatal Alcohol Exposure Impairs the Placenta\u2013Cortex Transcriptomic Signature, Leading to Dysregulation of Angiogenic Pathways"],"prefix":"10.3390","volume":"24","author":[{"given":"Camille","family":"Sautreuil","sequence":"first","affiliation":[{"name":"University Rouen Normandie, INSERM U1245, Team Epigenetics and Pathophysiology of Neurodevelopmental Disorders, 76183 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryline","family":"Lecointre","sequence":"additional","affiliation":[{"name":"University Rouen Normandie, INSERM U1245, Team Epigenetics and Pathophysiology of Neurodevelopmental Disorders, 76183 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Derambure","sequence":"additional","affiliation":[{"name":"University Rouen Normandie, INSERM U1245, Team Genetic Predisposition to Cancer, 76000 Rouen, France"},{"name":"Joint Genomics Facilities, Rouen University, 76183 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Brasse-Lagnel","sequence":"additional","affiliation":[{"name":"University Rouen Normandie, INSERM U1245, Team Epigenetics and Pathophysiology of Neurodevelopmental Disorders, 76183 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0183-5427","authenticated-orcid":false,"given":"Philippe","family":"Leroux","sequence":"additional","affiliation":[{"name":"University Rouen Normandie, INSERM U1245, Team Epigenetics and Pathophysiology of Neurodevelopmental Disorders, 76183 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Laquerri\u00e8re","sequence":"additional","affiliation":[{"name":"University Rouen Normandie, INSERM U1245, Team Epigenetics and Pathophysiology of Neurodevelopmental Disorders, 76183 Rouen, France"},{"name":"Department of Pathology, Rouen University Hospital, 76183 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00ebl","family":"Nicolas","sequence":"additional","affiliation":[{"name":"University Rouen Normandie, INSERM U1245, Team Genomics for Brain Disorders, 76183 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Gil","sequence":"additional","affiliation":[{"name":"INSERM UMR-S1144, Sorbonne Paris Cit\u00e9, Universit\u00e9 Paris Descartes, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel D.","family":"Savage","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, School of Medicine, University of New Mexico, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2858-148X","authenticated-orcid":false,"given":"St\u00e9phane","family":"Marret","sequence":"additional","affiliation":[{"name":"University Rouen Normandie, INSERM U1245, Team Epigenetics and Pathophysiology of Neurodevelopmental Disorders, 76183 Rouen, France"},{"name":"Department of Neonatal Paediatrics and Intensive Care, Rouen University Hospital, University Rouen Normandie and CHU Rouen, 76183 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florent","family":"Marguet","sequence":"additional","affiliation":[{"name":"University Rouen Normandie, INSERM U1245, Team Epigenetics and Pathophysiology of Neurodevelopmental Disorders, 76183 Rouen, France"},{"name":"Department of Pathology, Rouen University Hospital, 76183 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4081-6704","authenticated-orcid":false,"given":"Anthony","family":"Falluel-Morel","sequence":"additional","affiliation":[{"name":"University Rouen Normandie, INSERM U1245, Team Epigenetics and Pathophysiology of Neurodevelopmental Disorders, 76183 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7176-1320","authenticated-orcid":false,"given":"Bruno J.","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"University Rouen Normandie, INSERM U1245, Team Epigenetics and Pathophysiology of Neurodevelopmental Disorders, 76183 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1001\/jamapediatrics.2017.2232","article-title":"Fetal Alcohol Spectrum Disorder-high rates, high needs, high time for action","volume":"171","author":"Chudley","year":"2017","journal-title":"JAMA Pediatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/S1474-4422(19)30150-4","article-title":"Clinical presentation, diagnosis, and management of fetal alcohol spectrum disorder","volume":"18","author":"Wozniak","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1542\/peds.2014-2171","article-title":"Misdiagnosis and missed diagnoses in foster and adopted children with prenatal alcohol 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