Gestational Hypoxia and Programing of Lung Metabolism

Rood, Kristiana; López, Vanessa; Frano, Michael R. La; Fiehn, Oliver; Zhang, Li; Blood, Arlin B.; Wilson, Sean

doi:10.3389/fphys.2019.01453

Cited by 9 publications

(6 citation statements)

References 101 publications

(168 reference statements)

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“…These are also the essential mechanisms for developmental programming. Similar studies have emphasized that epigenetic modifications and programming in response to environmental stimuli are critical in achieving appropriate gene expression patterns, especially in specific lung tissues in relation to environmental signals [25,26]. This review focuses on aspects associated with chronic intrauterine hypoxia and epigenetic programming in bronchopulmonary dysplasia.…”

Section: Introductionmentioning

confidence: 91%

Intrauterine Hypoxia and Epigenetic Programming in Lung Development and Disease

et al. 2021

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Clinically, intrauterine hypoxia is the foremost cause of perinatal morbidity and developmental plasticity in the fetus and newborn infant. Under hypoxia, deviations occur in the lung cell epigenome. Epigenetic mechanisms (e.g., DNA methylation, histone modification, and miRNA expression) control phenotypic programming and are associated with physiological responses and the risk of developmental disorders, such as bronchopulmonary dysplasia. This developmental disorder is the most frequent chronic pulmonary complication in preterm labor. The pathogenesis of this disease involves many factors, including aberrant oxygen conditions and mechanical ventilation-mediated lung injury, infection/inflammation, and epigenetic/genetic risk factors. This review is focused on various aspects related to intrauterine hypoxia and epigenetic programming in lung development and disease, summarizes our current knowledge of hypoxia-induced epigenetic programming and discusses potential therapeutic interventions for lung disease.

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Section: Introductionmentioning

confidence: 91%

Intrauterine Hypoxia and Epigenetic Programming in Lung Development and Disease

et al. 2021

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“…In the heart, eNOS expression was increased at the protein and decreased at the gene expression level [ 85 ]. The effect of hypoxia on eNOS expression depends on the duration of hypoxia because increased ROS production may interfere with the bioavailability of NO during prolonged hypoxia [ 58 ]. The dynamic relationship between ROS and NO determines vascular tone because the hypoxia-induced increase in ROS, and thus the foetal ROS/NO ratio, potentiates peripheral vasoconstriction and redistribution of blood flow from the peripheral circulation to the vital organs, such as the brain and heart [ 112 ].…”

Section: Prenatal Hypoxiamentioning

confidence: 99%

“…Under normoxia, HIF-1α is rapidly degraded, but if the partial pressure of oxygen decreases, it is stabilized and accumulates in the cells. HIF-1α maintains oxygen homeostasis by regulating the expression of hundreds of genes and interacts with pathways involved in the regulation of the cardiovascular system, such as the chemoreflex, sympathetic drive [ 54 ], renin-angiotensin-aldosterone system (RAAS) [ 55 , 56 ], and local vessel wall components such as nitric oxide (NO) [ 57 , 58 , 59 ] and endothelin-1 [ 60 , 61 ]. Moreover, HIF directly interacts with the circadian clock because HIF-1α controls the expression of several canonical circadian genes and the response to hypoxia is gated by the circadian clock [ 62 ].…”

Section: Introductionmentioning

confidence: 99%

Prenatal Hypoxia Affects Foetal Cardiovascular Regulatory Mechanisms in a Sex- and Circadian-Dependent Manner: A Review

Šutovska

Babarikova

Zeman

et al. 2022

IJMS

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Prenatal hypoxia during the prenatal period can interfere with the developmental trajectory and lead to developing hypertension in adulthood. Prenatal hypoxia is often associated with intrauterine growth restriction that interferes with metabolism and can lead to multilevel changes. Therefore, we analysed the effects of prenatal hypoxia predominantly not associated with intrauterine growth restriction using publications up to September 2021. We focused on: (1) The response of cardiovascular regulatory mechanisms, such as the chemoreflex, adenosine, nitric oxide, and angiotensin II on prenatal hypoxia. (2) The role of the placenta in causing and attenuating the effects of hypoxia. (3) Environmental conditions and the mother’s health contribution to the development of prenatal hypoxia. (4) The sex-dependent effects of prenatal hypoxia on cardiovascular regulatory mechanisms and the connection between hypoxia-inducible factors and circadian variability. We identified that the possible relationship between the effects of prenatal hypoxia on the cardiovascular regulatory mechanism may vary depending on circadian variability and phase of the days. In summary, even short-term prenatal hypoxia significantly affects cardiovascular regulatory mechanisms and programs hypertension in adulthood, while prenatal programming effects are not only dependent on the critical period, and sensitivity can change within circadian oscillations.

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“…Even though normal pulmonary development occurs in the uterus in a relatively hypoxic environment, compression in the fetal CDH lungs by the abdominal content could decrease the lung perfusion, causing a drop in the nutrients and oxygen delivery. Previous studies demonstrated that excessive prenatal lung hypoxia has significant and lasting effects on the pulmonary vasculature, structurally and functionally [ 34 , 35 , 36 ]. On the other hand, cells undergo anaerobic metabolism under hypoxia [ 37 ], putting them at risk of energetic failure if unable to produce enough ATP for cellular functions [ 38 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

Lung Metabolomics Profiling of Congenital Diaphragmatic Hernia in Fetal Rats

et al. 2021

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Congenital diaphragmatic hernia (CDH) is characterized by the herniation of abdominal contents into the thoracic cavity during the fetal period. This competition for fetal thoracic space results in lung hypoplasia and vascular maldevelopment that can generate severe pulmonary hypertension (PH). The detailed mechanisms of CDH pathogenesis are yet to be understood. Acknowledgment of the lung metabolism during the in-utero CDH development can help to discern the CDH pathophysiology changes. Timed-pregnant dams received nitrofen or vehicle (olive oil) on E9.5 day of gestation. All fetal lungs exposed to nitrofen or vehicle control were harvested at day E21.5 by C-section and processed for metabolomics analysis using nuclear magnetic resonance (NMR) spectroscopy. The three groups analyzed were nitrofen-CDH (NCDH), nitrofen-control (NC), and vehicle control (VC). A total of 64 metabolites were quantified and subjected to statistical analysis. The multivariate analysis identified forty-four metabolites that were statistically different between the three groups. The highest Variable importance in projection (VIP) score (>2) metabolites were lactate, glutamate, and adenosine 5′-triphosphate (ATP). Fetal CDH lungs have changes related to oxidative stress, nucleotide synthesis, amino acid metabolism, glycerophospholipid metabolism, and glucose metabolism. This work provides new insights into the molecular mechanisms behind the CDH pathophysiology and can explore potential novel treatment targets for CDH patients.

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Gestational Hypoxia and Programing of Lung Metabolism

Cited by 9 publications

References 101 publications

Intrauterine Hypoxia and Epigenetic Programming in Lung Development and Disease

Intrauterine Hypoxia and Epigenetic Programming in Lung Development and Disease

Prenatal Hypoxia Affects Foetal Cardiovascular Regulatory Mechanisms in a Sex- and Circadian-Dependent Manner: A Review

Lung Metabolomics Profiling of Congenital Diaphragmatic Hernia in Fetal Rats

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