{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:44:19Z","timestamp":1790639059049,"version":"4.1.0"},"reference-count":37,"publisher":"Cambridge University Press (CUP)","issue":"3","license":[{"start":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T00:00:00Z","timestamp":1676505600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["J Dev Orig Health Dis"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Fetal growth restriction (FGR) is associated with increased risk of developing non-communicable diseases. We have a placenta-specific nanoparticle gene therapy protocol that increases placental expression of\n                    <jats:italic>human insulin-like growth factor 1<\/jats:italic>\n                    (\n                    <jats:italic>hIGF1<\/jats:italic>\n                    ), for the treatment of FGR\n                    <jats:italic>in utero<\/jats:italic>\n                    . We aimed to characterize the effects of FGR on hepatic gluconeogenesis pathways during early stages of FGR establishment, and determine whether placental nanoparticle-mediated\n                    <jats:italic>hIGF1<\/jats:italic>\n                    therapy treatment\u00a0could resolve differences in the FGR fetus. Female Hartley guinea pigs (dams) were fed either a Control or Maternal Nutrient Restriction (MNR) diet using established protocols. At GD30-33, dams underwent ultrasound guided, transcutaneous, intraplacental injection of\n                    <jats:italic>hIGF1<\/jats:italic>\n                    nanoparticle or PBS (sham) and were sacrificed 5 days post-injection. Fetal liver tissue was fixed and snap frozen for morphology and gene expression analysis. In female and male fetuses, liver weight as a percentage of body weight was reduced by MNR, and not changed with\n                    <jats:italic>hIGF1<\/jats:italic>\n                    nanoparticle treatment. In female fetal livers, expression of\n                    <jats:italic>hypoxia inducible factor 1<\/jats:italic>\n                    (\n                    <jats:italic>Hif1\u03b1<\/jats:italic>\n                    ) and\n                    <jats:italic>tumor necrosis factor<\/jats:italic>\n                    (\n                    <jats:italic>Tnf\u03b1<\/jats:italic>\n                    ) were increased in MNR compared to Control, but reduced in MNR +\n                    <jats:italic>hIGF1<\/jats:italic>\n                    compared to MNR. In male fetal liver, MNR increased expression of\n                    <jats:italic>Igf1<\/jats:italic>\n                    and decreased expression of\n                    <jats:italic>Igf2<\/jats:italic>\n                    compared to Control.\n                    <jats:italic>Igf1<\/jats:italic>\n                    and\n                    <jats:italic>Igf2<\/jats:italic>\n                    expression was restored to Control levels in the MNR +\n                    <jats:italic>hIGF1<\/jats:italic>\n                    group. This data provides further insight into the sex-specific mechanistic adaptations seen in FGR fetuses and demonstrates that disruption to fetal developmental mechanisms may be returned to normal by treatment of the placenta.\n                  <\/jats:p>","DOI":"10.1017\/s2040174423000016","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T02:47:35Z","timestamp":1676515655000},"page":"325-332","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":20,"title":["Placental nanoparticle gene therapy normalizes gene expression changes in the fetal liver associated with fetal growth restriction in a fetal sex-specific manner"],"prefix":"10.1017","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3867-7784","authenticated-orcid":false,"given":"Rebecca L.","family":"Wilson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendal K.","family":"Stephens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen N.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2023,2,16]]},"reference":[{"key":"S2040174423000016_ref10","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/35093050","article-title":"Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1","volume":"413","author":"Yoon","year":"2001","journal-title":"Nature"},{"key":"S2040174423000016_ref13","doi-asserted-by":"crossref","first-page":"R920","DOI":"10.1152\/ajpregu.00197.2015","article-title":"Limited capacity for glucose oxidation in fetal sheep with intrauterine growth restriction","volume":"309","author":"Brown","year":"2015","journal-title":"Am J Physiol-Regul Integr Comp 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The Author(s), 2023. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https:\/\/creativecommons.org\/licenses\/by\/4.0\/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}