Prenatal Hypoxia Reduces Mitochondrial Protein Levels and Cytochrome c Oxidase Activity in Offspring Guinea Pig Hearts

Al-Hasan, Yazan; Pinkas, Gerard A.; Thompson, Loren P.

doi:10.1177/1933719113518981

Cited by 23 publications

(21 citation statements)

References 78 publications

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“…Mitochondria account for~95% of the O 2 consumed in cardiac cells, which rely predominantly on oxidative phosphorylation for generation of the ATP supply (47). In fetal and adult hearts, HPX reduces respiratory enzyme activities (4,5,36), which reduces mitochondrial function and may contribute to cardiomyopathies and cardiac failure (16,48,49). Prenatal HPX had no effect on baseline OCR or normalized OCR associated with ATP synthesis in isolated heart cells of male or female offspring, although H ϩ leak was slightly decreased in males.…”

Section: Discussionmentioning

confidence: 99%

“…We recently focused on the effects of prenatal hypoxia on mitochondrial function of fetal and offspring hearts. We reported that prenatal hypoxia decreases cytochrome c oxidase activity in fetal (4) and offspring (5) guinea pig heart ventricles as evidence of prenatal hypoxia as a stimulus that impairs cardiac mitochondrial function. Attenuation of mitochondrial function is well documented to increase risk of heart dysfunction in the adult (16,48).…”

Section: Introductionmentioning

confidence: 91%

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Prenatal hypoxia impairs cardiac mitochondrial and ventricular function in guinea pig offspring in a sex-related manner

Thompson

Chen

Polster

et al. 2018

American Journal of Physiology-Regulatory, Integrative and Comp

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Adverse intrauterine conditions cause fetal growth restriction and increase the risk of adult cardiovascular disease. We hypothesize that intrauterine hypoxia impairs fetal heart function, is sustained after birth, and manifests as both cardiac and mitochondrial dysfunction in offspring guinea pigs (GPs). Pregnant GPs were exposed to 10.5% O2 (HPX) at 50 days of gestation (full term = 65 days) or normoxia (NMX) for the duration of the pregnancy. Pups were allowed to deliver vaginally and raised in a NMX environment. At 90 days of age, mean arterial pressure (MAP) was measured in anesthetized GPs. NMX and prenatally HPX offspring underwent echocardiographic imaging for in vivo measurement of left ventricular cardiac morphology and function, and O2 consumption rates and complex IV enzyme activity were measured from isolated cardiomyocytes and mitochondria, respectively. Prenatal HPX increased ( P < 0.01) MAP (52.3 ± 1.3 and 58.4 ± 1.1 mmHg in NMX and HPX, respectively) and decreased ( P < 0.05) stroke volume (439.8 ± 54.5 and 289.4 ± 15.8 μl in NMX and HPX, respectively), cardiac output (94.4 ± 11.2 and 67.3 ± 3.8 ml/min in NMX and HPX, respectively), ejection fraction, and fractional shortening in male, but not female, GPs. HPX had no effect on left ventricular wall thickness or end-diastolic volume in either sex. HPX reduced mitochondrial maximal respiration and respiratory reserve capacity and complex IV activity rates in hearts of male, but not female, GPs. Prenatal HPX is a programming stimulus that increases MAP and decreases cardiac and mitochondrial function in male offspring. Sex-related differences in the contractile and mitochondrial responses suggest that female GPs are protected from cardiovascular programming of prenatal HPX.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Prenatal hypoxia impairs cardiac mitochondrial and ventricular function in guinea pig offspring in a sex-related manner

Thompson

Chen

Polster

et al. 2018

American Journal of Physiology-Regulatory, Integrative and Comp

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“…; Al‐Hasan et al . ). However, the female counterpart has been relatively less investigated with only a few studies available in the literature.…”

Section: Discussionmentioning

confidence: 99%

“…Secondly, we demonstrated that resveratrol had similar metabolic and cardioprotective effects, independent of sex, indicating its therapeutic potential in the treatment of metabolic and cardiovascular diseases in both sexes. The effects of prenatal hypoxia on long-term adverse metabolic and cardiovascular outcomes have been previously characterized in adult male offspring (Li et al 2003;Dolinsky et al 2011;Giussani et al 2012;Al-Hasan et al 2014). However, the female counterpart has been relatively less investigated with only a few studies available in the literature.…”

Section: Discussionmentioning

confidence: 99%

Effect of resveratrol on metabolic and cardiovascular function in male and female adult offspring exposed to prenatal hypoxia and a high‐fat diet

Shah

Reyes

Morton

et al. 2015

The Journal of Physiology

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Key pointsr Prenatal hypoxia, a common outcome of many pregnancy complications, predisposes offspring to chronic diseases in later life.r We investigated the effect of prenatal hypoxia, on a background of a high-fat diet, on metabolic and cardiac function in adult male and female rat offspring. We also examined the therapeutic role of resveratrol supplementation in preventing metabolic and cardiac dysfunction.r Prenatal hypoxia impaired both metabolic and cardiac function in male and only cardiac function in female rat offspring. We also observed that male rat offspring were more susceptible to metabolic and cardiac dysfunction as compared with their female counterparts; this provides evidence of sexual dichotomy in the fetal programming of diseases due to prenatal hypoxia.r Resveratrol supplementation in the diet improved metabolic and cardiac function independent of sex; this provides evidence of a possible therapeutic role of resveratrol in susceptible male and female rat offspring exposed to prenatal hypoxia.Abstract Prenatal hypoxia, a common outcome of pregnancy complications, predisposes offspring to the development of metabolic and cardiovascular disorders in later life. We have previously observed that resveratrol improved cardiovascular and metabolic health in adult male rat offspring exposed to prenatal hypoxia and a postnatal high-fat (HF) diet; however, the effects of resveratrol in female rat offspring are not known. Our aim was to identify the mechanism(s) by which resveratrol may prevent metabolic and cardiac dysfunction in both male and female rat offspring exposed to prenatal hypoxia and a postnatal HF diet. Offspring that experienced normoxia or hypoxia in utero were fed a HF diet or a HF diet supplemented with resveratrol for 9 weeks following weaning. Body composition, metabolic function, in vivo cardiac function and ex vivo cardiac susceptibility to ischaemia-reperfusion (I/R) injury were assessed at 12 weeks of age. Prenatal hypoxia impaired metabolic function in male, but not female, rat offspring fed a HF diet and this was improved by resveratrol supplementation. Prenatal hypoxia also led to reduced recovery from cardiac I/R injury in male, and to a lesser extent in female, rat offspring fed a HF diet. Indices of cardiac oxidative stress after I/R were enhanced in both male and female rat offspring exposed to prenatal hypoxia. Resveratrol improved cardiac recovery from I/R injury and attenuated superoxide levels in both male and female rat offspring. In conclusion, prenatal hypoxia impaired metabolic and cardiac function in a sex-specific manner. Resveratrol supplementation may improve metabolic and cardiovascular health in adult male and female rat offspring exposed to prenatal hypoxia.

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“…The decreased cytochrome c oxidase activity of hypoxic fetal guinea pig ventricles was sustained in hearts of prenatally hypoxic guinea pig offspring, suggesting mitochondrial programming in offspring hearts (Al‐Hasan et al . ).…”

Section: Introductionmentioning

confidence: 97%

Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

Morrison

Botting

Darby

et al. 2018

The Journal of Physiology

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108

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Over 30 years ago Professor David Barker first proposed the theory that events in early life could explain an individual's risk of non-communicable disease in later life: the developmental origins of health and disease (DOHaD) hypothesis. During the 1990s the validity of the DOHaD hypothesis was extensively tested in a number of human populations and the mechanisms underpinning it characterised in a range of experimental animal models. Over the past decade, researchers have sought to use this mechanistic understanding of DOHaD to develop therapeutic interventions during pregnancy and early life to improve adult health. A variety of animal models have been used to develop and evaluate interventions, each with strengths and limitations. It is becoming apparent that effective translational research requires that the animal paradigm selected mirrors the tempo of human fetal growth and development as closely as possible so that the effect of a perinatal insult and/or therapeutic intervention can be fully assessed. The guinea pig is one such animal model that over the past two decades has demonstrated itself to be a very useful platform for these important reproductive studies. This review highlights similarities in the in utero development between humans and guinea pigs, the strengths and limitations of the guinea pig as an experimental model of DOHaD and the guinea pig's potential to enhance clinical therapeutic innovation to improve human health.

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Prenatal Hypoxia Reduces Mitochondrial Protein Levels and Cytochrome c Oxidase Activity in Offspring Guinea Pig Hearts

Cited by 23 publications

References 78 publications

Prenatal hypoxia impairs cardiac mitochondrial and ventricular function in guinea pig offspring in a sex-related manner

Prenatal hypoxia impairs cardiac mitochondrial and ventricular function in guinea pig offspring in a sex-related manner

Effect of resveratrol on metabolic and cardiovascular function in male and female adult offspring exposed to prenatal hypoxia and a high‐fat diet

Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

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