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dc.contributor.authorNapso, Tina
dc.contributor.authorLean, Samantha C
dc.contributor.authorLu, Minhui
dc.contributor.authorMort, Emily J
dc.contributor.authorDesforges, Michelle
dc.contributor.authorMoghimi, Ali
dc.contributor.authorBartels, Beverly
dc.contributor.authorEl-Bacha, Tatiana
dc.contributor.authorFowden, Abigail L
dc.contributor.authorCamm, Emily J
dc.contributor.authorSferruzzi-Perri, Amanda
dc.date.accessioned2022-02-15T13:00:17Z
dc.date.available2022-02-15T13:00:17Z
dc.date.issued2022-04
dc.date.submitted2021-08-17
dc.identifier.issn1748-1708
dc.identifier.otherapha13795
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/334047
dc.descriptionFunder: Department of Physiology, Development and Neuroscience Seed Funding
dc.descriptionFunder: Isaac Newton Trust Research Grant
dc.descriptionFunder: Medical Research Council PhD Stipend
dc.descriptionFunder: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Fellowship
dc.description.abstractAIM: The current study investigated the impact of maternal obesity on placental phenotype in relation to fetal growth and sex. METHODS: Female C57BL6/J mice were fed either a diet high in fat and sugar or a standard chow diet, for 6 weeks prior to, and during, pregnancy. At day 19 of gestation, placental morphology and mitochondrial respiration and dynamics were assessed using high-resolution respirometry, stereology, and molecular analyses. RESULTS: Diet-induced maternal obesity increased the rate of small for gestational age fetuses in both sexes, and increased blood glucose concentrations in offspring. Placental weight, surface area, and maternal blood spaces were decreased in both sexes, with reductions in placental trophoblast volume, oxygen diffusing capacity, and an increased barrier to transfer in males only. Despite these morphological changes, placental mitochondrial respiration was unaffected by maternal obesity, although the influence of fetal sex on placental respiratory capacity varied between dietary groups. Moreover, in males, but not females, maternal obesity increased mitochondrial complexes (II and ATP synthase) and fission protein DRP1 abundance. It also reduced phosphorylated AMPK and capacity for lipid synthesis, while increasing indices of oxidative stress, specifically in males. In females only, placental mitochondrial biogenesis and capacity for lipid synthesis, were both enhanced. The abundance of uncoupling protein-2 was decreased by maternal obesity in both fetal sexes. CONCLUSION: Maternal obesity exerts sex-dependent changes in placental phenotype in association with alterations in fetal growth and substrate supply. These findings may inform the design of personalized lifestyle interventions or therapies for obese pregnant women.
dc.languageen
dc.publisherWiley
dc.subjectREGULAR PAPER
dc.subjectREGULAR PAPERS
dc.subjectfetus
dc.subjectmitochondria
dc.subjectobesity
dc.subjectobesogenic diet
dc.subjectplacenta
dc.subjectsex
dc.titleDiet-induced maternal obesity impacts feto-placental growth and induces sex-specific alterations in placental morphology, mitochondrial bioenergetics, dynamics, lipid metabolism and oxidative stress in mice.
dc.typeArticle
dc.date.updated2022-02-15T13:00:17Z
prism.publicationNameActa Physiol (Oxf)
dc.identifier.doi10.17863/CAM.81459
dcterms.dateAccepted2022-02-01
rioxxterms.versionofrecord10.1111/apha.13795
rioxxterms.versionAO
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidLean, Samantha C [0000-0001-6434-0782]
dc.contributor.orcidDesforges, Michelle [0000-0002-1066-4586]
dc.contributor.orcidMoghimi, Ali [0000-0001-9578-2612]
dc.contributor.orcidEl-Bacha, Tatiana [0000-0003-0809-0218]
dc.contributor.orcidCamm, Emily J [0000-0003-0767-2697]
dc.contributor.orcidSferruzzi-Perri, Amanda [0000-0002-4931-4233]
dc.identifier.eissn1748-1716
pubs.funder-project-idMedical Research Council (MR/R022690/1)
cam.issuedOnline2022-02-15


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