{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T02:07:57Z","timestamp":1780970877486,"version":"3.54.1"},"reference-count":32,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T00:00:00Z","timestamp":1755302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Perinatal research faces significant challenges in understanding placental biology and maternal\u2013fetal interactions due to limited access to human tissues and the lack of reliable models. Emerging technologies, such as liquid biopsy and single-cell analysis, offer novel, non-invasive approaches to investigate these processes. This scoping review explores the current applications of these technologies in placental development and the diagnosis of pregnancy complications, identifying research gaps and providing recommendations for future studies. Methods: This review adhered to PRISMA-ScR guidelines. Studies were selected based on their focus on liquid biopsy or single-cell analysis in perinatal research, particularly related to placental development and pregnancy complications such as preeclampsia, preterm birth, and fetal growth restriction. A systematic search was conducted in PubMed, Scopus, and Web of Science for studies published in the last ten years. Data extraction and thematic synthesis were performed to identify diagnostic applications, monitoring strategies, and biomarker identification. Results: Twelve studies were included, highlighting the transformative potential of liquid biopsy and single-cell analysis in perinatal research. Liquid biopsy technologies, such as cfDNA and cfRNA analysis, provided non-invasive methods for real-time monitoring of placental function and early identification of complications. Extracellular vesicles (EVs) emerged as biomarkers for conditions like preeclampsia. Single-cell RNA sequencing (scRNA-seq) revealed cellular diversity and pathways critical to placental health, offering insights into processes such as vascular remodeling and trophoblast invasion. While promising, challenges such as high costs, technical complexity, and the need for standardization limit their clinical integration. Conclusion: Liquid biopsy and single-cell analysis are revolutionizing perinatal research, offering non-invasive tools to understand and manage complications like preeclampsia. Overcoming challenges in accessibility and standardization will be key to unlocking their potential for personalized care, enabling better outcomes for mothers and children worldwide.<\/jats:p>","DOI":"10.3390\/diagnostics15162056","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T07:53:12Z","timestamp":1755503592000},"page":"2056","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Liquid Biopsy and Single-Cell Technologies in Maternal\u2013Fetal Medicine: A Scoping Review of Non-Invasive Molecular Approaches"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8737-8935","authenticated-orcid":false,"given":"Irma Eloisa","family":"Monroy-Mu\u00f1oz","sequence":"first","affiliation":[{"name":"Department of Reproductive and Perinatal Health Research, Instituto Nacional de Perinatolog\u00eda Isidro Espinosa de los Reyes, Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnatan","family":"Torres-Torres","sequence":"additional","affiliation":[{"name":"Department of Reproductive and Perinatal Health Research, Instituto Nacional de Perinatolog\u00eda Isidro Espinosa de los Reyes, Mexico City 11000, Mexico"},{"name":"Obstetric and Gynecology Department, Hospital General de M\u00e9xico Dr. Eduardo Liceaga, Mexico City 06720, Mexico"},{"name":"Iberoamerican Research Network in Obstetrics, Gynecology and Translational Medicine, Mexico City 11560, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes","family":"Rojas-Zepeda","sequence":"additional","affiliation":[{"name":"Maternal-Fetal Department, Instituto Materno Infantil del Estado de Mexico, Toluca 50170, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Rafael","family":"Villafan-Bernal","sequence":"additional","affiliation":[{"name":"Iberoamerican Research Network in Obstetrics, Gynecology and Translational Medicine, Mexico City 11560, Mexico"},{"name":"Laboratory of Immunogenomics and Metabolic Diseases, Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7276-8463","authenticated-orcid":false,"given":"Salvador","family":"Espino-y-Sosa","sequence":"additional","affiliation":[{"name":"Department of Reproductive and Perinatal Health Research, Instituto Nacional de Perinatolog\u00eda Isidro Espinosa de los Reyes, Mexico City 11000, Mexico"},{"name":"Iberoamerican Research Network in Obstetrics, Gynecology and Translational Medicine, Mexico City 11560, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deyanira","family":"Baca","sequence":"additional","affiliation":[{"name":"Obstetric and Gynecology Department, Hospital General de M\u00e9xico Dr. Eduardo Liceaga, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaira Alexi","family":"Camacho-Martinez","sequence":"additional","affiliation":[{"name":"Obstetric and Gynecology Department, Hospital General de M\u00e9xico Dr. Eduardo Liceaga, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Perez-Duran","sequence":"additional","affiliation":[{"name":"Department of Reproductive and Perinatal Health Research, Instituto Nacional de Perinatolog\u00eda Isidro Espinosa de los Reyes, Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4529-8296","authenticated-orcid":false,"given":"Juan Mario","family":"Solis-Paredes","sequence":"additional","affiliation":[{"name":"Department of Reproductive and Perinatal Health Research, Instituto Nacional de Perinatolog\u00eda Isidro Espinosa de los Reyes, Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9551-9021","authenticated-orcid":false,"given":"Guadalupe","family":"Estrada-Gutierrez","sequence":"additional","affiliation":[{"name":"Immunobiochemistry Department, Instituto Nacional de Perinatologia, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8733-1800","authenticated-orcid":false,"given":"Elsa Romelia","family":"Moreno-Verduzco","sequence":"additional","affiliation":[{"name":"Department of Reproductive and Perinatal Health Research, Instituto Nacional de Perinatolog\u00eda Isidro Espinosa de los Reyes, Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4711-3857","authenticated-orcid":false,"given":"Raigam","family":"Martinez-Portilla","sequence":"additional","affiliation":[{"name":"Iberoamerican Research Network in Obstetrics, Gynecology and Translational Medicine, Mexico City 11560, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Deng, F., Lei, J., Qiu, J., Zhao, C., Wang, X., Li, M., Sun, M., Zhang, M., and Gao, Q. 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