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Syncytiotrophoblast cells (STB), formed by the fusion of mononuclear cytotrophoblasts (CTB), constitute the interface between the foetus and the mother and are essential for all of these functions. We performed transcriptome analysis of human placental samples from two control groups\u2014live births (LB), and stillbirths (SB) with a clinically recognised cause\u2014and from our study group, idiopathic stillbirths (iSB). We identified 1172 DEGs in iSB, when comparing with the LB group; however, when we compared iSB with the SB group, only 15 and 12 genes were down- and upregulated in iSB, respectively. An assessment of these DEGs identified 15 commonly downregulated genes in iSB. Among these, several syncytiotrophoblast markers, like genes from the PSG and CSH families, as well as ALPP, KISS1, and CRH, were significantly downregulated in placental samples from iSB. The transcriptome analysis revealed underlying differences at a molecular level involving the syncytiotrophoblast. This suggests that defects in the syncytial layer may underlie unexplained stillbirths, therefore offering insights to improve clinical obstetrics practice.<\/jats:p>","DOI":"10.3390\/ijms25105180","type":"journal-article","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T03:21:04Z","timestamp":1715311264000},"page":"5180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Syncytiotrophoblast Markers Are Downregulated in Placentas from Idiopathic Stillbirths"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6479-4132","authenticated-orcid":false,"given":"Sara","family":"Vasconcelos","sequence":"first","affiliation":[{"name":"Genetics Service, Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0293-8540","authenticated-orcid":false,"given":"Ioannis","family":"Moustakas","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands"},{"name":"Sequencing Analysis Support Core, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9447-1548","authenticated-orcid":false,"given":"Miguel R.","family":"Branco","sequence":"additional","affiliation":[{"name":"Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK"}]},{"given":"Susana","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine and Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"given":"Carla","family":"Cani\u00e7ais","sequence":"additional","affiliation":[{"name":"Genetics Service, Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Talia van der","family":"Helm","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3977-3946","authenticated-orcid":false,"given":"Carla","family":"Ramalho","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"},{"name":"Department of Obstetrics and Gynaecology, Faculty of Medicine and Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"given":"Cristina Joana","family":"Marques","sequence":"additional","affiliation":[{"name":"Genetics Service, Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Susana M. Chuva de","family":"Sousa Lopes","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands"}]},{"given":"Sofia","family":"D\u00f3ria","sequence":"additional","affiliation":[{"name":"Genetics Service, Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e110","DOI":"10.1097\/AOG.0000000000003719","article-title":"Management of Stillbirth","volume":"135","author":"Metz","year":"2020","journal-title":"Obstet. 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