Prenatal alcohol exposure is associated with altered feto-placental blood flow and sex-specific placental changes

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dc.contributor.authorSteane, S.E.
dc.contributor.authorEdwards, C.
dc.contributor.authorCavanagh, E.
dc.contributor.authorVanderpeet, C.
dc.contributor.authorKubler, J.M.
dc.contributor.authorAkison, L.K.
dc.contributor.authorCuffe, J.S.M.
dc.contributor.authorGallo, L.A.
dc.contributor.authorMoritz, K.M.
dc.contributor.authorClifton, V.L.
dc.date.issued2025
dc.description.abstractBACKGROUND. Prenatal alcohol exposure (PAE) around conception in preclinical models results in placental insufficiency, likely contributing to offspring abnormalities. Altered placental DNA methylation (DNAm) and gene expression suggest epigenetic mechanisms, perhaps involving impacts on methyl donor levels. PAE around conception in women is common but placental effects are rarely examined. This cohort study investigated associations between PAE around conception and intake/plasma measures of the methyl donors folate and choline, feto-placental blood flow, and placental growth measures, gene expression, and DNAm. METHODS. Pregnant participants delivered at Mater Mothers’ Hospital, Brisbane, Queensland, Australia (n = 411). Dietary intake of choline and folate were calculated and plasma concentrations measured using mass spectrometry (MS) and clinical immunoanalyzer, respectively. Cerebroplacental ratio (CPR) was calculated using Doppler measurements. Placentas were weighed/measured at delivery and samples used to quantify methyl donors (MS), global DNAm (ELISA), and gene expression (quantitative PCR). Data were compared between control/abstinent and PAE groups, by fetal sex. RESULTS. A CPR <5th-centile, indicating fetal brain sparing because of placental insufficiency, was found in 2% of controls and 18% of the PAE group, mostly male fetuses (63%). Compared with controls, male PAE placentas had reduced mean thickness and placental growth factor mRNA and DNAm, whereas female PAE placentas had increased S-adenosylmethionine and a trend toward increased DNAm. CONCLUSION. PAE around conception is associated with reduced CPR and altered placental growth measures, particularly in males, with potential implications for future health.
dc.description.statementofresponsibilitySarah E. Steane, Christopher Edwards, Erika Cavanagh, Chelsea Vanderpeet, Jade M. Kubler, Lisa K. Akison, James S.M. Cuffe, Linda A. Gallo, Karen M. Moritz, Vicki L. Clifton
dc.identifier.citationJCI Insight, 2025; 10(3):e186096-1-e186096-21
dc.identifier.doi10.1172/jci.insight.186096
dc.identifier.issn2379-3708
dc.identifier.issn2379-3708
dc.identifier.orcidClifton, V.L. [0000-0002-4892-6748]
dc.identifier.urihttps://hdl.handle.net/2440/145816
dc.language.isoen
dc.publisherAmerican Society for Clinical investigation
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1191217
dc.rights© 2025, Steane et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
dc.source.urihttps://doi.org/10.1172/jci.insight.186096
dc.subjectAlcohol Drinking
dc.subjectCohort Studies
dc.subjectDNA Methylation
dc.subjectFolic Acid
dc.subjectMale
dc.subjectPlacenta
dc.subjectPlacental Circulation
dc.subjectPlacental Insufficiency
dc.subjectPregnancy
dc.subjectPrenatal Exposure Delayed Effects
dc.subjectSex Factors
dc.subjectalcohol drinking; cohort analysis; DNA methylation; placental insufficiency; prenatal exposure delayed effects; sex factors
dc.titlePrenatal alcohol exposure is associated with altered feto-placental blood flow and sex-specific placental changes
dc.typeJournal article
pubs.publication-statusPublished

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