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    Sexual dimorphism of mitochondrial function in the hypoxic Guinea pig placenta

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    Author
    Song, H.
    Telugu, B.P.
    Thompson, L.P.
    Date
    2019
    Journal
    Biology of Reproduction
    Publisher
    Oxford University Press
    Type
    article
    
    Metadata
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    See at
    https://doi.org/10.1093/biolre/ioy167
    Abstract
    Placental hypoxia can stimulate oxidative stress and mitochondrial dysfunction reducing placental efficiency and inducing fetal growth restriction (FGR). We hypothesized that chronic hypoxia inhibits mitochondrial function in the placenta as an underlying cause of cellular mechanisms contributing to FGR. Pregnant guinea pigs were exposed to either normoxia (NMX) or hypoxia (HPX; 10.5% O2) at 25 day gestation until term (65 day). Guinea pigs were anesthetized, and fetuses and placentas were excised at either mid (40 day) or late gestation (64 day), weighed, and placental tissue stored at −80°C until assayed. Mitochondrial DNA content, protein expression of respiratory Complexes I-V, and nitration and activity rates of Complexes I and IV were measured in NMX and HPX male (N = 6 in each treatment) and female (N = 6 in each treatment) placentas. Mitochondrial density was not altered by HPX in either mid- or late-term placentas. In mid gestation, HPX slightly increased expression of Complexes I-III and V in male placentas only, but had no effect on either Complex I or IV activity rates or nitrotyrosine expression. In late gestation, HPX significantly decreased CI/CIV activity rates and increased CI/CIV nitration in male but not female placentas exhibiting a sexual dimorphism. Complex I-V expression was reduced from mid to late gestation in both male and female placentas regardless of treatment. We conclude that chronic HPX decreases mitochondrial function by inhibiting Complex I/IV activity via increased peroxynitrite in a sex-related manner. Further, there may be a progressive decrease in energy metabolism of placental cell types with gestation that increases the vulnerability of placental function to intrauterine stress. Copyright The Author(s) 2018.
    Keyword
    Hypoxia
    Mitochondria
    Pregnancy
    Respiratory complex
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85058812898&doi=10.1093%2fbiolre%2fioy167&partnerID=40&md5=02297ca54d025ca37f8420bb4024fbcd; http://hdl.handle.net/10713/10209
    ae974a485f413a2113503eed53cd6c53
    10.1093/biolre/ioy167
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