Trophoblast organoids as a model for maternal–fetal interactions during human placentation

The placenta is the extraembryonic organ that supports the fetus during intrauterine life. Although placental dysfunction results in major disorders of pregnancy with immediate and lifelong consequences for the mother and child, our knowledge of the human placenta is limited owing to a lack of funct...

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Veröffentlicht in:	Nature (London) Jg. 564; H. 7735; S. 263 - 267
Hauptverfasser:	Turco, Margherita Y., Gardner, Lucy, Kay, Richard G., Hamilton, Russell S., Prater, Malwina, Hollinshead, Michael S., McWhinnie, Alasdair, Esposito, Laura, Fernando, Ridma, Skelton, Helen, Reimann, Frank, Gribble, Fiona M., Sharkey, Andrew, Marsh, Steven G. E., O’Rahilly, Stephen, Hemberger, Myriam, Burton, Graham J., Moffett, Ashley
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 01.12.2018 Nature Publishing Group
Schlagworte:	13 14 38 631/136 631/1647 Analysis Antigens Bioinformatics Cell Differentiation Cell Movement Chorionic gonadotropin Chorionic Gonadotropin - metabolism Chorionic gonadotropins Decidua Decidua - cytology Deoxyribonucleic acid DNA DNA Methylation Epithelium Female Fetuses Glycoproteins Gonadotropins Growth Differentiation Factor 15 - metabolism Histocompatibility antigen HLA HLA antigens HLA Antigens - metabolism Hormones Humanities and Social Sciences Humans Implantation Letter Leukocytes Mass spectrometry Mass spectroscopy Maternal-fetal exchange Maternal-Fetal Relations Models, Biological multidisciplinary Organoids Organoids - cytology Organoids - metabolism Organoids - physiology Peptides Physiological aspects Physiological research Pituitary (anterior) Placenta Placental hormones Placentation Pregnancy Pregnancy-Specific beta 1-Glycoproteins - metabolism Principal components analysis Science Science (multidisciplinary) Scientific imaging Secretion Spectroscopy Stem cells Surgical implants Three dimensional analysis Tissue Culture Techniques Tissue typing Transcriptome - genetics Transplants & implants Trophectoderm Trophoblasts Trophoblasts - cytology Trophoblasts - metabolism Trophoblasts - physiology
ISSN:	0028-0836, 1476-4687, 1476-4687
Online-Zugang:	Volltext
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Zusammenfassung:	The placenta is the extraembryonic organ that supports the fetus during intrauterine life. Although placental dysfunction results in major disorders of pregnancy with immediate and lifelong consequences for the mother and child, our knowledge of the human placenta is limited owing to a lack of functional experimental models 1 . After implantation, the trophectoderm of the blastocyst rapidly proliferates and generates the trophoblast, the unique cell type of the placenta. In vivo, proliferative villous cytotrophoblast cells differentiate into two main sub-populations: syncytiotrophoblast, the multinucleated epithelium of the villi responsible for nutrient exchange and hormone production, and extravillous trophoblast cells, which anchor the placenta to the maternal decidua and transform the maternal spiral arteries 2 . Here we describe the generation of long-term, genetically stable organoid cultures of trophoblast that can differentiate into both syncytiotrophoblast and extravillous trophoblast. We used human leukocyte antigen (HLA) typing to confirm that the organoids were derived from the fetus, and verified their identities against four trophoblast-specific criteria 3 . The cultures organize into villous-like structures, and we detected the secretion of placental-specific peptides and hormones, including human chorionic gonadotropin (hCG), growth differentiation factor 15 (GDF15) and pregnancy-specific glycoprotein (PSG) by mass spectrometry. The organoids also differentiate into HLA-G + extravillous trophoblast cells, which vigorously invade in three-dimensional cultures. Analysis of the methylome reveals that the organoids closely resemble normal first trimester placentas. This organoid model will be transformative for studying human placental development and for investigating trophoblast interactions with the local and systemic maternal environment. An in vitro system that generates three-dimensional cultures of extraembryonic fetal trophoblast cells that differentiate into the two main types of trophoblast can be used to study human placental development.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Joint last authors who contributed equally to the study
ISSN:	0028-0836 1476-4687 1476-4687
DOI:	10.1038/s41586-018-0753-3