{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:10:59Z","timestamp":1790046659992,"version":"4.0.1"},"reference-count":81,"publisher":"Portland Press Ltd.","issue":"17","license":[{"start":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T00:00:00Z","timestamp":1629244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,9,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Fetal growth restriction (FGR) is a complication of pregnancy that reduces birth weight, markedly increases infant mortality and morbidity and is associated with later-life cardiometabolic disease. No specific treatment is available for FGR. Placentas of human FGR infants have low abundance of sodium-coupled neutral amino acid transporter 2 (Slc38a2\/SNAT2), which supplies the fetus with amino acids required for growth. We determined the mechanistic role of placental Slc38a2\/SNAT2 deficiency in the development of restricted fetal growth, hypothesizing that placenta-specific Slc38a2 knockdown causes FGR in mice. Using lentiviral transduction of blastocysts with a small hairpin RNA (shRNA), we achieved 59% knockdown of placental Slc38a2, without altering fetal Slc38a2 expression. Placenta-specific Slc38a2 knockdown reduced near-term fetal and placental weight, fetal viability, trophoblast plasma membrane (TPM) SNAT2 protein abundance, and both absolute and weight-specific placental uptake of the amino acid transport System A tracer, 14C-methylaminoisobutyric acid (MeAIB). We also measured human placental SLC38A2 gene expression in a well-defined term clinical cohort and found that SLC38A2 expression was decreased in late-onset, but not early-onset FGR, compared with appropriate for gestational age (AGA) control placentas. The results demonstrate that low placental Slc38a2\/SNAT2 causes FGR and could be a target for clinical therapies for late-onset FGR.<\/jats:p>","DOI":"10.1042\/cs20210575","type":"journal-article","created":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T10:24:38Z","timestamp":1629282278000},"page":"2049-2066","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Placenta-specific\n                    <i>Slc38a2<\/i>\n                    \/SNAT2 knockdown causes fetal growth restriction in mice"],"prefix":"10.1042","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7537-3264","authenticated-orcid":false,"given":"Owen\u00a0R.","family":"Vaughan","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, U.S.A."},{"name":"Department of Maternal and Fetal Medicine, Elizabeth Garrett Anderson Institute for Women\u2019s Health, University College London WC1E 6HX, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Maksym","sequence":"additional","affiliation":[{"name":"Department of Maternal and Fetal Medicine, Elizabeth Garrett Anderson Institute for Women\u2019s Health, University College London WC1E 6HX, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Barentsen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russel\u00a0V.","family":"Anthony","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Animal Reproduction and Biotechnology Laboratory, Colorado State University, Fort Collins, CO 80523, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas\u00a0L.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Cell Biology and Physiology, Wright State University Boonshoft School of Medicine, Dayton, OH 45435, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara\u00a0L.","family":"Hillman","sequence":"additional","affiliation":[{"name":"Department of Maternal and Fetal Medicine, Elizabeth Garrett Anderson Institute for Women\u2019s Health, University College London WC1E 6HX, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Spencer","sequence":"additional","affiliation":[{"name":"Department of Maternal and Fetal Medicine, Elizabeth Garrett Anderson Institute for Women\u2019s Health, University College London WC1E 6HX, U.K."},{"name":"Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9NL, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna\u00a0L.","family":"David","sequence":"additional","affiliation":[{"name":"Department of Maternal and Fetal Medicine, Elizabeth Garrett Anderson Institute for Women\u2019s Health, University College London WC1E 6HX, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrick\u00a0J.","family":"Rosario","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa\u00a0L.","family":"Powell","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, U.S.A."},{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Jansson","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2021,8,31]]},"reference":[{"key":"2021113011232535100_B1","doi-asserted-by":"publisher","first-page":"S855","DOI":"10.1016\/j.ajog.2017.12.004","article-title":"Evidence-based national guidelines for the management of suspected fetal growth restriction: comparison, consensus, and controversy","volume":"218","author":"McCowan","year":"2018","journal-title":"Am. 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