{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:26:29Z","timestamp":1792787189027,"version":"4.5.0"},"reference-count":81,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T00:00:00Z","timestamp":1722556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R21-HD104797"],"award-info":[{"award-number":["R21-HD104797"]}]},{"name":"National Institutes of Health","award":["P51-OD-011092"],"award-info":[{"award-number":["P51-OD-011092"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Organoids"],"abstract":"<jats:p>First trimester placental development comprises some of the most critical yet understudied events that impact fetal development. Improper placentation leads to a host of health issues that not only impact the fetal period but also influence offspring throughout their lives. Thus, a paradigm to study early placental development is necessary, and this has spurred on the pursuit of new in vitro model systems that recapitulate specific aspects of placentation. One of the most complex and translationally valid models to arise are organoids, three-dimensional structures comprising multiple differentiated cell types that originate from a common progenitor population. Trophoblasts are the progenitor cells of the placenta, serving as the proliferative base for placental development. Recent advances have enabled the derivation of organoids from primary tissue, yet access to first trimester human samples is ethically constrained; derivation from established trophoblast stem cell lines is an alternative source. Organoids have already proven useful in generating insights into molecular events that underlie trophoblast differentiation, with the identification of new cell subtypes that are primed to differentiate down different paths. In this review, (1) we recap early pregnancy development events, (2) provide an overview of the cellular complexity of the placenta, (3) discuss the generation of organoids from tissue versus cellular sources, (4) highlight the value of translational animal models, and (5) focus on the complexities of the molecular regulation of trophoblast organoid development, differentiation, and function.<\/jats:p>","DOI":"10.3390\/organoids3030012","type":"journal-article","created":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T16:14:58Z","timestamp":1722615298000},"page":"174-193","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Trophoblast Organoids: Capturing the Complexity of Early Placental Development In Vitro"],"prefix":"10.3390","volume":"3","author":[{"given":"Brady M.","family":"Wessel","sequence":"first","affiliation":[{"name":"Division of Reproductive and Developmental Science, Oregon National Primate Research Center (ONPRC), Oregon Health and Science University (OHSU), Beaverton, OR 97006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna N.","family":"Castro","sequence":"additional","affiliation":[{"name":"Division of Reproductive and Developmental Science, Oregon National Primate Research Center (ONPRC), Oregon Health and Science University (OHSU), Beaverton, OR 97006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria H. J.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Division of Reproductive and Developmental Science, Oregon National Primate Research Center (ONPRC), Oregon Health and Science University (OHSU), Beaverton, OR 97006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.ajog.2010.08.009","article-title":"The \u201cGreat Obstetrical Syndromes\u201d Are Associated with Disorders of Deep Placentation","volume":"204","author":"Brosens","year":"2011","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.placenta.2005.12.006","article-title":"The Uterine Spiral Arteries in Human Pregnancy: Facts and Controversies","volume":"27","author":"Pijnenborg","year":"2006","journal-title":"Placenta"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Baergen, R.N., Burton, G.J., and Kaplan, C.G. (2022). Benirschke\u2019s Pathology of the Human Placenta, Springer International Publishing.","DOI":"10.1007\/978-3-030-84725-8"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/rmb2.12347","article-title":"Unique Features and Emerging in Vitro Models of Human Placental Development","volume":"19","author":"Shibata","year":"2020","journal-title":"Reprod. Med. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.placenta.2009.01.002","article-title":"Evidence for Transcriptional Activity in the Syncytiotrophoblast of the Human Placenta","volume":"30","author":"Ellery","year":"2009","journal-title":"Placenta"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e00135","DOI":"10.1016\/j.heliyon.2016.e00135","article-title":"Histomorphometric Parameters of Normal Full Term Placenta of Sudanese Women","volume":"2","author":"Abdalla","year":"2016","journal-title":"Heliyon"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1203\/00006450-199808000-00015","article-title":"Chloride Transport across Syncytiotrophoblast Microvillous Membrane of First Trimester Human Placenta","volume":"44","author":"Doughty","year":"1998","journal-title":"Pediatr. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.devcel.2024.01.023","article-title":"Single-Cell Assessment of Primary and Stem Cell-Derived Human Trophoblast Organoids as Placenta-Modeling Platforms","volume":"59","author":"Shannon","year":"2024","journal-title":"Dev. Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"dev199749","DOI":"10.1242\/dev.199749","article-title":"Characterization of Primary Models of Human Trophoblast","volume":"148","author":"Sheridan","year":"2021","journal-title":"Development"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.stem.2022.04.004","article-title":"Stem-Cell-Derived Trophoblast Organoids Model Human Placental Development and Susceptibility to Emerging Pathogens","volume":"29","author":"Karvas","year":"2022","journal-title":"Cell Stem Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1038\/s41422-018-0066-y","article-title":"Single-Cell RNA-Seq Reveals the Diversity of Trophoblast Subtypes and Patterns of Differentiation in the Human Placenta","volume":"28","author":"Liu","year":"2018","journal-title":"Cell Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/s41586-018-0698-6","article-title":"Single-Cell Reconstruction of the Early Maternal\u2013Fetal Interface in Humans","volume":"563","author":"Efremova","year":"2018","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"E7710","DOI":"10.1073\/pnas.1612335113","article-title":"Notch1 Controls Development of the Extravillous Trophoblast Lineage in the Human Placenta","volume":"113","author":"Haider","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","first-page":"297","article-title":"Development of the Human Placenta in the First Three Months of Gestation","volume":"94","author":"Hamilton","year":"1960","journal-title":"J. Anat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.placenta.2017.06.007","article-title":"The Cytotrophoblastic Shell and Complications of Pregnancy","volume":"60","author":"Burton","year":"2017","journal-title":"Placenta"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s41586-023-05869-0","article-title":"Spatial Multiomics Map of Trophoblast Development in Early Pregnancy","volume":"616","author":"Arutyunyan","year":"2023","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1530\/REP-09-0092","article-title":"Regulation of Vascular Growth and Function in the Human Placenta","volume":"138","author":"Burton","year":"2009","journal-title":"Reproduction"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"305","DOI":"10.2350\/09-08-0692-OA.1","article-title":"Syncytial Knots as a Reflection of Placental Maturity: Reference Values for 20 to 40 Weeks\u2019 Gestational Age","volume":"13","author":"Loukeris","year":"2010","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1038\/s41588-023-01647-w","article-title":"Single-Nucleus Multi-Omic Profiling of Human Placental Syncytiotrophoblasts Identifies Cellular Trajectories during Pregnancy","volume":"56","author":"Wang","year":"2024","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.stemcr.2016.01.006","article-title":"What Is Trophoblast? A Combination of Criteria Define Human First-Trimester Trophoblast","volume":"6","author":"Lee","year":"2016","journal-title":"Stem Cell Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"dev199840","DOI":"10.1242\/dev.199840","article-title":"Cell Trajectory Modeling Identifies a Primitive Trophoblast State Defined by BCAM Enrichment","volume":"149","author":"Shannon","year":"2022","journal-title":"Development"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3657","DOI":"10.1242\/dev.120.12.3657","article-title":"Integrin Switching Regulates Normal Trophoblast Invasion","volume":"120","author":"Damsky","year":"1994","journal-title":"Development"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1093\/humrep\/14.2.496","article-title":"Are Human Placental Bed Giant Cells Merely Aggregates of Small Mononuclear Trophoblast Cells? An Ultrastructural and Immunocytochemical Study","volume":"14","author":"Skepper","year":"1999","journal-title":"Human. Reprod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.placenta.2021.08.053","article-title":"A Re-Examination of the Origins of Placental Bed Giant Cells","volume":"114","author":"Jones","year":"2021","journal-title":"Placenta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"R129","DOI":"10.1530\/REP-20-0354","article-title":"Animal Models of Human Pregnancy and Placentation: Alternatives to the Mouse","volume":"160","author":"Carter","year":"2020","journal-title":"Reproduction"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1293\/tox.2013-0060","article-title":"A Comparison of the Histological Structure of the Placenta in Experimental Animals","volume":"27","author":"Furukawa","year":"2014","journal-title":"J. Toxicol. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e23526","DOI":"10.1002\/ajp.23526","article-title":"Rhesus Macaque Fetal and Placental Growth Demographics: A Resource for Laboratory Animal Researchers","volume":"85","author":"Roberts","year":"2023","journal-title":"Am. J. Primatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1002\/mrm.26052","article-title":"Functional Imaging of the Nonhuman Primate Placenta with Endogenous Blood Oxygen Level\u2013Dependent Contrast","volume":"76","author":"Schabel","year":"2016","journal-title":"Magn. Reson. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/(SICI)1097-0185(199607)245:3<525::AID-AR9>3.0.CO;2-Q","article-title":"Macaque Intra-Arterial Trophoblast and Extravillous Trophoblast of the Cell Columns and Cytotrophoblastic Shell Express Neural Cell Adhesion Molecule (NCAM)","volume":"245","author":"Blankenship","year":"1996","journal-title":"Anat. Rec."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1053\/plac.2001.0626","article-title":"Structure of Anchoring Villi and the Trophoblastic Shell in the Human, Baboon and Macaque Placenta","volume":"22","author":"Enders","year":"2001","journal-title":"Placenta"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Burton, G.J., and Jauniaux, E. (2023). The Human Placenta: New Perspectives on Its Formation and Function during Early Pregnancy. Proc. R. Soc. B Biol. Sci., 290.","DOI":"10.1098\/rspb.2023.0191"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Carter, A.M., Enders, A.C., and Pijnenborg, R. (2015). The Role of Invasive Trophoblast in Implantation and Placentation of Primates. Philos. Trans. R. Soc. B Biol. Sci., 370.","DOI":"10.1098\/rstb.2014.0070"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1095\/biolreprod58.3.728","article-title":"The Rhesus Monkey Analogue of Human Lymphocyte Antigen-G Is Expressed Primarily in Villous Syncytiotrophoblasts1","volume":"58","author":"Slukvin","year":"1998","journal-title":"Biol. Reprod."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.devcel.2023.03.012","article-title":"Identifying a Dynamic Transcriptomic Landscape of the Cynomolgus Macaque Placenta during Pregnancy at Single-Cell Resolution","volume":"58","author":"Jiang","year":"2023","journal-title":"Dev. Cell"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Schmidt, J.K., Keding, L.T., Block, L.N., Wiepz, G.J., Koenig, M.R., Meyer, M.G., Dusek, B.M., Kroner, K.M., Bertogliat, M.J., and Kallio, A.R. (2020). Placenta-Derived Macaque Trophoblast Stem Cells: Differentiation to Syncytiotrophoblasts and Extravillous Trophoblasts Reveals Phenotypic Reprogramming. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-76313-w"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1210\/jcem-39-3-457","article-title":"Specific Radioimmunoassay of Chorionic Gonadotropin During Implantation in Rhesus Monkeys","volume":"39","author":"Hodgen","year":"1974","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Raha, S. (2024). Trophoblasts Methods and Protocols, Springer. Methods in Molecular Biology.","DOI":"10.1007\/978-1-0716-3495-0"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/S0143-4004(03)00142-5","article-title":"Trophoblast Viability in Perfused Term Placental Tissue and Explant Cultures Limited to 7\u201324 Hours","volume":"24","author":"Malek","year":"2003","journal-title":"Placenta"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"R1116","DOI":"10.1152\/ajpregu.2001.280.4.R1116","article-title":"The Functional Regeneration of Syncytiotrophoblast in Cultured Explants of Term Placenta","volume":"280","author":"Sibley","year":"2001","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/BF02113808","article-title":"Viability of the Human Placental Villi in Organ Culture","volume":"234","author":"Ogino","year":"1984","journal-title":"Arch. Gynecol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1093\/humrep\/12.2.379","article-title":"Morphological Analysis of Degeneration and Regeneration of Syncytiotrophoblast in First Trimester Placental Villi during Organ Culture","volume":"12","author":"Palmer","year":"1997","journal-title":"Hum. Reprod."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/978-1-0716-3746-3_4","article-title":"In Vitro Culturing of Human Term Placental Explants","volume":"Volume 2781","year":"2024","journal-title":"Maternal Placental Interface"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1093\/humrep\/den066","article-title":"Villous Explant Culture Using Early Gestation Tissue from Ongoing Pregnancies with Known Normal Outcomes: The Effect of Oxygen on Trophoblast Outgrowth and Migration","volume":"23","author":"Seeho","year":"2008","journal-title":"Human. Reprod."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.stem.2017.11.004","article-title":"Derivation of Human Trophoblast Stem Cells","volume":"22","author":"Okae","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e52504","DOI":"10.7554\/eLife.52504","article-title":"Derivation of Trophoblast Stem Cells from Na\u00efve Human Pluripotent Stem Cells","volume":"9","author":"Dong","year":"2020","journal-title":"eLife"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1089\/scd.2007.0020","article-title":"Blastocyst-Derived Trophoblast Stem Cells from the Rhesus Monkey","volume":"16","author":"Vandevoort","year":"2007","journal-title":"Stem Cells Dev."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Matsumoto, S., Porter, C.J., Ogasawara, N., Iwatani, C., Tsuchiya, H., Seita, Y., Chang, Y.-W., Okamoto, I., Saitou, M., and Ema, M. (2020). Establishment of Macaque Trophoblast Stem Cell Lines Derived from Cynomolgus Monkey Blastocysts. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-63602-7"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/s41586-018-0753-3","article-title":"Trophoblast Organoids as a Model for Maternal-Fetal Interactions during Human Placentation","volume":"564","author":"Turco","year":"2018","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.stemcr.2018.07.004","article-title":"Self-Renewing Trophoblast Organoids Recapitulate the Developmental Program of the Early Human Placenta","volume":"11","author":"Haider","year":"2018","journal-title":"Stem Cell Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1109\/TBME.2020.3038466","article-title":"Ultra-High-Resolution 3D Optical Coherence Tomography Reveals Inner Structures of Human Placenta-Derived Trophoblast Organoids","volume":"68","author":"Deloria","year":"2021","journal-title":"IEEE Trans. Biomed. Eng."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1038\/s41467-024-45279-y","article-title":"Trophoblast Stem Cell-Based Organoid Models of the Human Placental Barrier","volume":"15","author":"Hori","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e79794","DOI":"10.7554\/eLife.79794","article-title":"Innate Immune Signaling in Trophoblast and Decidua Organoids Defines Differential Antiviral Defenses at the Maternal-Fetal Interface","volume":"11","author":"Yang","year":"2022","journal-title":"eLife"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"jcs261528","DOI":"10.1242\/jcs.261528","article-title":"Trophoblast Organoids with Physiological Polarity Model Placental Structure and Function","volume":"137","author":"Yang","year":"2023","journal-title":"J. Cell Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e1501462","DOI":"10.1126\/sciadv.1501462","article-title":"A Three-Dimensional Culture System Recapitulates Placental Syncytiotrophoblast Development and Microbial Resistance","volume":"2","author":"McConkey","year":"2016","journal-title":"Sci. Adv."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3441","DOI":"10.1038\/s41596-020-0381-x","article-title":"Establishment and Differentiation of Long-Term Trophoblast Organoid Cultures from the Human Placenta","volume":"15","author":"Sheridan","year":"2020","journal-title":"Nat. Protoc."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"17864","DOI":"10.1073\/pnas.2002449117","article-title":"TEAD4 Ensures Postimplantation Development by Promoting Trophoblast Self-Renewal: An Implication in Early Human Pregnancy Loss","volume":"117","author":"Saha","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1177\/1479164117738442","article-title":"Interrelationship of Canonical and Non-Canonical Wnt Signalling Pathways in Chronic Metabolic Diseases","volume":"15","author":"Ackers","year":"2018","journal-title":"Diab Vasc. Dis. Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Kn\u00f6fler, M., and Pollheimer, J. (2013). Human Placental Trophoblast Invasion and Differentiation: A Particular Focus on Wnt Signaling. Front. Genet., 4.","DOI":"10.3389\/fgene.2013.00190"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.3892\/mmr.2017.6718","article-title":"Wnt\/\u03b2-Catenin Signaling Pathway in Trophoblasts and Abnormal Activation in Pre-eclampsia (Review)","volume":"16","author":"Zhang","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Meinhardt, G., Saleh, L., Otti, G.R., Haider, S., Velicky, P., Fiala, C., Pollheimer, J., and Kn\u00f6fler, M. (2016). Wingless Ligand 5a Is a Critical Regulator of Placental Growth and Survival. Sci. Rep., 6.","DOI":"10.1038\/srep28127"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e2120667119","DOI":"10.1073\/pnas.2120667119","article-title":"Transforming Growth Factor-\u03b2 Signaling Governs the Differentiation Program of Extravillous Trophoblasts in the Developing Human Placenta","volume":"119","author":"Haider","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"20354","DOI":"10.1073\/pnas.2013559117","article-title":"Role of Hippo Signaling Pathway in Early Placental Development","volume":"117","author":"Soncin","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.devcel.2010.09.011","article-title":"The Hippo Signaling Pathway in Development and Cancer","volume":"19","author":"Pan","year":"2010","journal-title":"Dev. Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/s41392-022-01191-9","article-title":"The Hippo Signalling Pathway and Its Implications in Human Health and Diseases","volume":"7","author":"Fu","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"13562","DOI":"10.1073\/pnas.2002630117","article-title":"Pivotal Role of the Transcriptional Co-Activator YAP in Trophoblast Stemness of the Developing Human Placenta","volume":"117","author":"Meinhardt","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e2204069119","DOI":"10.1073\/pnas.2204069119","article-title":"Hippo Signaling Cofactor, WWTR1, at the Crossroads of Human Trophoblast Progenitor Self-Renewal and Differentiation","volume":"119","author":"Ray","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Kopan, R. (2012). Notch Signaling. Cold Spring Harb. Perspect. Biol., 4.","DOI":"10.1101\/cshperspect.a011213"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1007\/s00018-022-04285-3","article-title":"WNT and NOTCH Signaling in Human Trophoblast Development and Differentiation","volume":"79","author":"Dietrich","year":"2022","journal-title":"Cell Mol. Life Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"dev202152","DOI":"10.1242\/dev.202152","article-title":"NOTCH3 Signalling Controls Human Trophoblast Stem Cell Expansion and Differentiation","volume":"150","author":"Dietrich","year":"2023","journal-title":"Development"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.placenta.2015.01.009","article-title":"Expression Pattern and Function of Notch2 in Different Subtypes of First Trimester Cytotrophoblast","volume":"36","author":"Plessl","year":"2015","journal-title":"Placenta"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1210\/en.2013-1455","article-title":"Notch Signaling Plays a Critical Role in Motility and Differentiation of Human First-Trimester Cytotrophoblasts","volume":"155","author":"Haider","year":"2014","journal-title":"Endocrinology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3390\/organoids1020009","article-title":"Single-Cell Atlas of Patient-Derived Trophoblast Organoids in Ongoing Pregnancies","volume":"1","author":"Schaffers","year":"2022","journal-title":"Organoids"},{"key":"ref_73","unstructured":"Jones, T.M., and Montero, F.J. (2024). Chorionic Villus Sampling. StatPearls, StatPearls Publishing."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/tog.12850","article-title":"Pitfalls of Prenatal Diagnosis Associated with Mosaicism","volume":"25","author":"Reilly","year":"2023","journal-title":"Obstet. Gynaecol."},{"key":"ref_75","first-page":"38","article-title":"Development of a Nonhuman Primate Trophoblast Organoid Model Resource","volume":"31","author":"Wessel","year":"2024","journal-title":"Reprod. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1038\/s41366-018-0145-7","article-title":"Maternal High-Fat Diet Reversal Improves Placental Hemodynamics in a Nonhuman Primate Model of Diet-Induced Obesity","volume":"43","author":"Salati","year":"2019","journal-title":"Int. J. Obes."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Hirsch, A.J., Smith, J.L., Haese, N.N., Broeckel, R.M., Parkins, C.J., Kreklywich, C., DeFilippis, V.R., Denton, M., Smith, P.P., and Messer, W.B. (2017). Zika Virus Infection of Rhesus Macaques Leads to Viral Persistence in Multiple Tissues. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006219"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1007\/s00213-013-3417-x","article-title":"The Effects of Age at the Onset of Drinking to Intoxication and Chronic Ethanol Self-Administration in Male Rhesus Macaques","volume":"231","author":"Helms","year":"2014","journal-title":"Psychopharmacology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"F53","DOI":"10.1530\/REP-20-0153","article-title":"HYPOXIA AND REPRODUCTIVE HEALTH: Oxygen and Development of the Human Placenta","volume":"161","author":"Burton","year":"2021","journal-title":"Reproduction"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Chang, T.A., Bondarenko, G.I., Gerami-Naini, B., Drenzek, J.G., Durning, M., Garthwaite, M.A., Schmidt, J.K., and Golos, T.G. (2018). Trophoblast Differentiation, Invasion and Hormone Secretion in a Three-Dimensional in Vitro Implantation Model with Rhesus Monkey Embryos. Reprod. Biol. Endocrinol., 16.","DOI":"10.1186\/s12958-018-0340-3"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1038\/ncb3516","article-title":"Long-Term, Hormone-Responsive Organoid Cultures of Human Endometrium in a Chemically Defined Medium","volume":"19","author":"Turco","year":"2017","journal-title":"Nat. Cell Biol."}],"container-title":["Organoids"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2674-1172\/3\/3\/12\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:28:43Z","timestamp":1760110123000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2674-1172\/3\/3\/12"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,2]]},"references-count":81,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["organoids3030012"],"URL":"https:\/\/doi.org\/10.3390\/organoids3030012","relation":{},"ISSN":["2674-1172"],"issn-type":[{"value":"2674-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,2]]}}}