{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T05:37:20Z","timestamp":1765431440254,"version":"3.46.0"},"reference-count":65,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022099","name":"Cerebral Palsy Alliance","doi-asserted-by":"crossref","award":["PRG09231"],"award-info":[{"award-number":["PRG09231"]}],"id":[{"id":"10.13039\/501100022099","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Health and Medical Research Council of Australia","award":["1175843","2016688"],"award-info":[{"award-number":["1175843","2016688"]}]},{"name":"Victorian Government\u2019s Operational Infrastructure Support Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Early-onset fetal growth restriction (FGR) is associated with prolonged fetoplacental hypoxia and altered brain development, including deficits in hippocampal structure and function. Neuroprotective actions of lactoferrin have been described, mediated via anti-inflammatory and antioxidant properties. Here, we investigated whether the antenatal administration of lactoferrin (1) improves hippocampal structure, (2) promotes neuronal growth, and (3) mitigates neuroinflammation in the hippocampus of fetal sheep with FGR. Early-onset FGR was induced by performing single umbilical artery ligation surgery on ovine fetuses at ~89 days gestational age (dGA; term ~148 dGA), compared with appropriate for gestational age (AGA) controls. Lactoferrin supplementation to the ewe commenced at 95 dGA (oral, 36 g\/day) and continued until 127 dGA (fetal group) or birth (newborn group). Experimental fetal groups included control appropriate for gestational age (AGA; n = 8), FGR (n = 5), control + lactoferrin (AGA + Lacto; n = 6), and FGR + lactoferrin (FGR + Lacto; n = 6). In the fetal group, results showed that neither FGR nor lactoferrin altered hippocampal structure at 127 dGA. Lactoferrin exposure significantly increased neuronal abundance but also altered neuronal morphology. Lactoferrin increased the neurotrophic factor, brain-derived neurotrophic factor (BDNF) in the hippocampus. Lactoferrin exerted region-specific anti-inflammatory effects, with reduced total microglial cell count and resting microglia count in the Cornu Ammonis (CA)3 region only. In the newborn cohort, we observed increased circulating haematocrit concentration in early life. These findings support that antenatal lactoferrin has an anti-inflammatory effect in the fetal brain and increases fetal brain neurotrophic factor BDNF. Still, prolonged exposure during pregnancy may yield mixed effects on fetal brain development and haematological balance.<\/jats:p>","DOI":"10.3390\/cells14241951","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T13:51:46Z","timestamp":1765288306000},"page":"1951","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Does Antenatal Lactoferrin Protect Hippocampal Development in Ovine Fetuses with Growth Restriction?"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8292-4224","authenticated-orcid":false,"given":"Dahyun","family":"Kang","sequence":"first","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid","family":"Dudink","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8809-3448","authenticated-orcid":false,"given":"Tegan A.","family":"White","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4807-2340","authenticated-orcid":false,"given":"Amy E.","family":"Sutherland","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4257-3814","authenticated-orcid":false,"given":"Tamara","family":"Yawno","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC 3168, Australia"},{"name":"Department of Paediatrics, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yen","family":"Pham","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7383-6648","authenticated-orcid":false,"given":"Petra S.","family":"Huppi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Gynecology and Obstetrics University of Geneva, 1205 Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0093-8747","authenticated-orcid":false,"given":"St\u00e9phane V.","family":"Sizonenko","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Gynecology and Obstetrics University of Geneva, 1205 Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0451-8304","authenticated-orcid":false,"given":"Suzanne L.","family":"Miller","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1060-513X","authenticated-orcid":false,"given":"Beth J.","family":"Allison","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1002\/uog.26111","article-title":"Determinants of placental insufficiency in fetal growth restriction","volume":"61","author":"Melito","year":"2023","journal-title":"Ultrasound Obstet. 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