4.6 Article

Bioenergetics adaptations and redox homeostasis in pregnancy and related disorders

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MOLECULAR AND CELLULAR BIOCHEMISTRY
卷 476, 期 11, 页码 4003-4018

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SPRINGER
DOI: 10.1007/s11010-021-04215-0

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Pregnancy; Mitochondria; Mitochondrial dysfunction; Mitochondrial-targeted drugs

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Pregnancy involves significant metabolic demands that rely on mitochondrial function, particularly in the placenta. Understanding the dynamic changes in placental mitochondria throughout gestation is crucial for identifying potential therapeutic targets for pregnancy-related disorders. Targeting mitochondrial metabolism is an emerging approach for managing conditions such as preeclampsia.
Pregnancy is a challenging physiological process that involves maternal adaptations to the increasing energetics demands imposed by the growing conceptus. Failure to adapt to these requirements may result in serious health complications for the mother and the baby. The mitochondria are biosynthetic and energy-producing organelles supporting the augmented energetic demands of pregnancy. Evidence suggests that placental mitochondria display a dynamic phenotype through gestation. At early stages of pregnancy placental mitochondria are mainly responsible for the generation of metabolic intermediates and reactive oxygen species (ROS), while at later stages of gestation, the placental mitochondria exhibit high rates of oxygen consumption. This review describes the metabolic fingerprint of the placental mitochondria at different stages of pregnancy and summarises key signs of mitochondrial dysfunction in pathological pregnancy conditions, including preeclampsia, gestational diabetes and intrauterine growth restriction (IUGR). So far, the effects of placental-driven metabolic changes governing the metabolic adaptations occurring in different maternal tissues in both, healthy and pathological pregnancies, remain to be uncovered. Understanding the function and molecular aspects of the adaptations occurring in placental and maternal tissue's mitochondria will unveil potential targets for further therapeutic exploration that could address pregnancy-related disorders. Targeting mitochondrial metabolism is an emerging approach for regulating mitochondrial bioenergetics. This review will also describe the potential therapeutic use of compounds with a recognised effect on mitochondria, for the management of preeclampsia.

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