Diet-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.
Authors
Napso, Tina
Lu, Minhui
Mort, Emily J
Bartels, Beverly
Fowden, Abigail L
Publication Date
2022-04Journal Title
Acta Physiol (Oxf)
ISSN
1748-1708
Publisher
Wiley
Language
en
Type
Article
This Version
AO
VoR
Metadata
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Napso, T., Lean, S. C., Lu, M., Mort, E. J., Desforges, M., Moghimi, A., Bartels, B., et al. (2022). Diet-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.. Acta Physiol (Oxf) https://doi.org/10.1111/apha.13795
Description
Funder: Department of Physiology, Development and Neuroscience Seed Funding
Funder: Isaac Newton Trust Research Grant
Funder: Medical Research Council PhD Stipend
Funder: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Fellowship
Abstract
AIM: 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.
Keywords
REGULAR PAPER, REGULAR PAPERS, fetus, mitochondria, obesity, obesogenic diet, placenta, sex
Sponsorship
Medical Research Council (MR/R022690/1)
Identifiers
apha13795
External DOI: https://doi.org/10.1111/apha.13795
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334047
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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