Changes in mitochondrial respiration in the human placenta over gestation

Holland, Olivia J.; Hickey, Anthony J. R.; Alvsaker, Anna; Moran, Stéphanie; Hedges, Christopher P.; Chamley, Lawrence W.; Perkins, Anthony V.

doi:10.1016/j.placenta.2017.06.011

Cited by 52 publications

(41 citation statements)

References 49 publications

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“…Data analysis was conducted using Datlab software (Oroboros Instruments), with respiratory states expressed relative to tissue weight as described previously (Holland et al . ).…”

Section: Methodsmentioning

confidence: 97%

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Maternal selenium deficiency during pregnancy in mice increases thyroid hormone concentrations, alters placental function and reduces fetal growth

Hofstee

Bartho

McKeating

et al. 2019

The Journal of Physiology

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Key points Inappropriate intake of key micronutrients in pregnancy is known to alter maternal endocrine status, impair placental development and induce fetal growth restriction. Selenium is an essential micronutrient required for the function of approximately 25 important proteins. However, the specific effects of selenium deficiency during pregnancy on maternal, placental and fetal outcomes are poorly understood. The present study demonstrates that maternal selenium deficiency increases maternal triiodothyronine and tetraiodothyronine concentrations, reduces fetal blood glucose concentrations, and induces fetal growth restriction. Placental expression of key selenium‐dependent thyroid hormone converting enzymes were reduced, whereas the expression of key placental nutrient transporters was dysregulated. Selenium deficiency had minimal impact on selenium‐dependent anti‐oxidants but increased placental copper concentrations and expression of superoxide dismutase 1. These results highlight the idea that selenium deficiency during pregnancy may contribute to thyroid dysfunction, causing reduced fetal growth, that may precede programmed disease outcomes in offspring. Abstract Selenium is a trace element fundamental to diverse homeostatic processes, including anti‐oxidant regulation and thyroid hormone metabolism. Selenium deficiency in pregnancy is common and increases the risk of pregnancy complications including fetal growth restriction. Although altered placental formation may contribute to these poor outcomes, the mechanism by which selenium deficiency contributes to complications in pregnancy is poorly understood. Female C57BL/6 mice were randomly allocated to control (>190 µg kg–1, n = 8) or low selenium (<50 µg kg–1, n = 8) diets 4 weeks prior to mating and throughout gestation. Pregnant mice were killed at embryonic day 18.5 followed by collection of maternal and fetal tissue. Maternal and fetal plasma thyroid hormone concentrations were analysed, as was placental expression of key selenoproteins involved in thyroid metabolism and anti‐oxidant defences. Selenium deficiency increased plasma tetraiodothyronine and triiodothyronine concentrations. This was associated with a reduction in placental expression of key selenodependent deiodinases, DIO2 and DIO3. Placental expression of selenium‐dependent anti‐oxidants was unaffected by selenium deficiency. Selenium deficiency reduced fetal glucose concentrations, leading to reduced fetal weight. Placental glycogen content was increased within the placenta, as was Slc2a3 mRNA expression. This is the first study to demonstrate that selenium deficiency may reduce fetal weight through increased maternal thyroid hormone concentrations, impaired placental thyroid hormone metabolism and dysregulated placental nutrient transporter expression. The study suggests that the magnitude of selenium deficiency commonly reported in pregnant women may be sufficient to impair thyroid metabolism but not placental anti‐oxidant concentrations.

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“…Data analysis was conducted using Datlab software (Oroboros Instruments), with respiratory states expressed relative to tissue weight as described previously (Holland et al . ).…”

Section: Methodsmentioning

confidence: 97%

“…Mitochondrial respiration was assessed as described previously (Holland et al . ; Fisher et al . ) with minor modifications.…”

Section: Methodsmentioning

confidence: 99%

Maternal selenium deficiency during pregnancy in mice increases thyroid hormone concentrations, alters placental function and reduces fetal growth

Hofstee

Bartho

McKeating

et al. 2019

The Journal of Physiology

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“…As the fetus grows, the demands on placental energetics increase, yet total mass-specific uteroplacental O 2 consumption changes little, if at all, from mid to late gestation in sheep and humans (7,8). However, there are gestational changes in placental oxidative stress and expression of the mitochondrial-related proteins in several species (9)(10)(11)(12), which suggest that function of placental mitochondria changes developmentally to meet the increasing fetal demands for growth toward term.…”

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confidence: 99%

Placental mitochondria adapt developmentally and in response to hypoxia to support fetal growth

Sferruzzi‐Perri

Higgins

Vaughan

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Mitochondria respond to a range of stimuli and function in energy production and redox homeostasis. However, little is known about the developmental and environmental control of mitochondria in the placenta, an organ vital for fetal growth and pregnancy maintenance in eutherian mammals. Using respirometry and molecular analyses, the present study examined mitochondrial function in the distinct transport and endocrine zones of the mouse placenta during normal pregnancy and maternal inhalation hypoxia. The data show that mitochondria of the two zones adopt different strategies in modulating their respiration, substrate use, biogenesis, density, and efficiency to best support the growth and energy demands of fetoplacental tissues during late gestation in both normal and hypoxic conditions. The findings have important implications for environmentally induced adaptations in mitochondrial function in other tissues and for compromised human pregnancy in which hypoxia and alterations in placental mitochondrial function are associated with poor outcomes like fetal growth restriction.

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“…Pregnancy significantly affects function of mitochondria of the placenta up to 11 th gestational week and when maternal blood flow had increased both placental content of mitochondria and mitochondrial respiratory function are increased since the 12 th GW and onward, so metabolic plasticity of placental mitochondria has relevance to placentamediated diseases (7) and growing evidence indicates that mitochondrial impairment may contribute to pathogenesis of PE (8) .…”

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confidence: 99%

High Plasma Mitochondrial Dna Early in Pregnancy Is a Risk Factor for Development of Preeclampsia.

Kallaf¹

2019

IJAR

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Objectives: Estimation of plasma mitochondrial DNA (mtDNA) levels in primigravida during 1st trimester and evaluation of its relation to development and severity of preeclampsia (PE). Patients & Methods: The study included 44 PE women (PE group) and 10 women free pf PE (Control group). At the 1 st visit, all women underwent complete clinical examination and gave fasting blood sample for investigations. All women were asked to attend 4-weekly till delivery for evaluation of PE manifestations including increased systolic (SBP) and diastolic blood pressure (DBP) with proteinuria. SBP ≥160 mmHg and DBP ≥110 with proteinuria >2+ indicates severe PE and early-onset PE was diagnosed if manifestations appeared at <34 gestational weeks. Plasma levels of mtDNA were estimated using realtime PCR. Results: Seventeen women developed early-onset PE and 35 women had mild PE. Mean plasma levels of mtDNA were significantly higher in PE women than controls, in women developed early-onset PE than women developed late-onset PE and in women developed severe PE than those developed mild PE. Statistical analyses defined high 1st trimester plasma mtDNA as significant early predictor for development of PE and when combined with high SBP during 1st trimester as significant early predictor for severe PE. However, high plasma mtDNA during 1st trimester in young women as significant early predictor for development of early-onset PE Conclusion: High 1st trimester plasma level of mtDNA could be considered as a measure for mitochondrial dysfunction with subsequent liability to develop PE especially the early-onset type and severe manifestations.

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Changes in mitochondrial respiration in the human placenta over gestation

Cited by 52 publications

References 49 publications

Maternal selenium deficiency during pregnancy in mice increases thyroid hormone concentrations, alters placental function and reduces fetal growth

Maternal selenium deficiency during pregnancy in mice increases thyroid hormone concentrations, alters placental function and reduces fetal growth

Placental mitochondria adapt developmentally and in response to hypoxia to support fetal growth

High Plasma Mitochondrial Dna Early in Pregnancy Is a Risk Factor for Development of Preeclampsia.

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