{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:23:22Z","timestamp":1790234602537,"version":"4.1.0"},"reference-count":86,"publisher":"National Academy of Sciences","issue":"45","license":[{"start":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:00:00Z","timestamp":1730246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD094937"],"award-info":[{"award-number":["R01HD094937"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015509","name":"Missouri Department of Health and Senior Services","doi-asserted-by":"publisher","award":["#AOC23380006"],"award-info":[{"award-number":["#AOC23380006"]}],"id":[{"id":"10.13039\/100015509","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"HHS | NIH | National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R01ES025547"],"award-info":[{"award-number":["R01ES025547"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,11,5]]},"abstract":"<jats:p>Pregnant women are often prescribed or abuse opioid drugs. The placenta is likely the key to understanding how opioids cause adverse pregnancy outcomes. Maternal oxycodone (OXY) exposure of pregnant mice leads to disturbances in the layer of invasive parietal trophoblast giant cells (pTGC) that forms the interface between the placenta and uterus. These cells are analogous to extravillous trophoblasts of the human placenta. They are crucial to coordinating the metabolic needs of the conceptus with those of the mother and are primary participants in the placenta\u2013brain axis. Their large nuclear size, however, has precluded both single-cell (sc) and single-nucleus (sn) RNA-seq analyses beyond embryonic day (E) 8.5. Here, we compared the transcriptomes of placentas from pregnant mice exposed to OXY with unexposed controls at E12.5, with particular emphasis on the pTGC. The nonfluidic Parse snRNA-seq approach permitted characterization of the nuclear transcriptomes of all the major placental cell lineages and their presumed progenitors at E12.5. OXY exposure had a negligible effect on components of the placental labyrinth, including the two syncytial cell layers, but caused transcriptomic changes consistent with metabolic stress throughout the spongiotrophoblast. Most notably, there was loss of the majority of pTGC, whose normal gene expression is consistent with elevated energy demand relating to biosynthesis of multiple secretory products, especially hormones, and endoduplication of DNA. This unusual sensitivity of pTGC presumably puts the pregnancy and future health of the offspring at particular risk to OXY exposure.<\/jats:p>","DOI":"10.1073\/pnas.2412349121","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T14:02:39Z","timestamp":1730296959000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":9,"title":["Effects of oxycodone on placental lineages: Evidence from the transcriptome profile of mouse trophoblast giant cells"],"prefix":"10.1073","volume":"121","author":[{"given":"Zhen","family":"Lyu","sequence":"first","affiliation":[{"name":"Department of Electrical Engineering and Computer Science, University of Missouri, Columbia, MO 65211"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica A.","family":"Kinkade","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences. University of Missouri, Columbia, MO 65211"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan J.","family":"Bivens","sequence":"additional","affiliation":[{"name":"Department of Genomics Technology Core Facility, University of Missouri, Columbia, MO 65211"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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University of Missouri, Columbia, MO 65211"},{"name":"Institute for Data Science and Informatics, University of Missouri, Columbia, MO 65211"},{"name":"Department of Genetics Area Program, University of Missouri, Columbia, MO 65211"},{"name":"Thompson Center for Autism and Neurobehavioral Disorders, University of Missouri, Columbia, MO 65211"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,10,30]]},"reference":[{"key":"e_1_3_4_1_2","unstructured":"CDC Basics about opioid use during pregnancy (2019). https:\/\/www.cdc.gov\/opioid-use-during-pregnancy\/about\/?CDC_AAref_Val=https:\/\/www.cdc.gov\/pregnancy\/opioids\/basics.html. 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