Effects of ketamine on the fetal transcriptomic response to umbilical cord occlusion: comparison with hypoxic hypoxia in the cerebral cortex

Zarate, Miguel; Chang, Eileen I.; Wood, Charles E.

doi:10.1113/jp275661

Cited by 3 publications

(5 citation statements)

References 52 publications

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“…In the late-gestation fetus, umbilical cord occlusion poses an immediate threat to fetal survival, whereas transient hypoxic hypoxia is better R5 tolerated. Despite this logic, we found that the transcriptomics response to hypoxic hypoxia is more vigorous than the response to asphyxic hypoxia of the same magnitude (148). This difference is illustrated in Fig.…”

Section: Responses One Day After Hypoxiamentioning

confidence: 75%

“…We reasoned that it is important to understand whether a transient hypoxic hypoxia, lowering maternal Pa O 2 from 100 tõ 50 mmHg [equivalent to travel to 12,000-feet elevation (101)], disturbs gene expression in the fetal brain in the longer term, in this case 1 day later. We compared the responses at 1 day with responses at 1 h after hypoxic hypoxia, and we compared the responses to hypoxic hypoxia with the responses to asphyxic hypoxia (partial umbilical cord occlusion performed in such a way that the change in fetal Pa O 2 was similar to that caused by hypoxic hypoxia) (147,148). The assumption, from the perspective of the fetal physiologist, is that the fetus responds to changes in blood gases (decreased Pa O 2 or, in the case of asphyxic hypoxia, decreased Pa O 2 and increased Pa CO 2 ) and that, at the end of the hypoxic event, the fetus is returned to the prehypoxia functional state after the physiological response that redistributes combined ventricular output to the fetal brain and heart.…”

Section: Responses One Day After Hypoxiamentioning

confidence: 99%

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Current paradigms and new perspectives on fetal hypoxia: implications for fetal brain development in late gestation

Wood

Keller‐Wood

2019

American Journal of Physiology-Regulatory, Integrative and Comp

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The availability of oxygen to the fetus is limited by the route taken by oxygen from the atmosphere to fetal tissues, aided or diminished by pregnancy-associated changes in maternal physiology and, ultimately, a function of atmospheric pressure and composition of the mother’s inspired gas. Much of our understanding of the fetal physiological response to hypoxia comes from experiments designed to elucidate the cardiovascular and endocrine responses to transient hypoxia. Complementing this work is equally impactful research into the origins of intrauterine growth restriction in which animal models designed to restrict the transfer of oxygen from the maternal to the fetal circulation were used. A common assumption has been that outcomes measured after a period of hypoxia are related to cellular deprivation of oxygen and reoxygenation: an assumption based on a focus on what we can see “under the streetlights.” Recent studies demonstrate that availability of oxygen may not tell the whole story. Transient hypoxia in the fetal sheep stimulates transcriptomics responses that mirror inflammation. This response is accompanied by the appearance of bacteria in the fetal brain and other tissues, likely resulting from a hypoxia-stimulated release of bacteria from the placenta. The appearance of bacteria in the fetus after transient hypoxia complements the recent discovery of bacterial DNA in the normal human placenta and in the tissues of fetal sheep. An understanding of the mechanism of the physiological, cellular, and molecular responses to hypoxia requires an appreciation of stimuli other than cellular oxygen deprivation: stimuli that we would have never known about without looking “between the streetlights,” illuminating direct responses to the manipulated variables.

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Section: Responses One Day After Hypoxiamentioning

confidence: 75%

Section: Responses One Day After Hypoxiamentioning

confidence: 99%

Current paradigms and new perspectives on fetal hypoxia: implications for fetal brain development in late gestation

Wood

Keller‐Wood

2019

American Journal of Physiology-Regulatory, Integrative and Comp

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“…We have reported the surprising discovery that bacteria can enter the fetus after transient maternal hypoxia 9 . In several studies, we found that isobaric maternal ventilatory hypoxia stimulated an inflammation-like response in the fetal brain 10,11 and kidneys 12 that correspond to the transcriptomics and cellular response that would be expected after bacterial infection. Indeed, culture and nonculture-based techniques confirmed the appearance of bacteria in the fetal brain, and confirmed that the bacteria matched those found in the placenta 9 .…”

mentioning

confidence: 78%

“…Tissues were either flash frozen with liquid nitrogen for DNA and protein analysis, chilled on wet ice and immediately sent for culturing analysis, or fixed in 4% paraformaldehyde overnight (followed by dehydration and paraffin embedding) for histological analysis. These methods of specimen collection and preservation have been previously described 10 , 13 , 31 . The time course of inoculation, blood sampling, and euthanasia/tissue collection in study 2 was similar to that of study 1 13 .…”

Section: Methodsmentioning

confidence: 99%

Transfer of oral bacteria to the fetus during late gestation

Rodriguez

Paul

et al. 2021

Sci Rep

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The fetus develops in a privileged environment, as the placenta serves as both a gateway for nutrients and a barrier for pathogen transfer to the fetus. Regardless, recent evidence suggests the presence of bacterial DNA in both placenta and fetus, and we have reported that DNA and protein from small numbers of bacteria gain access to the fetus from the maternal bloodstream. Other routes of environmental bacterial transfer from the mother to fetus remain unknown, as well as the physiological relevance of their presence. In these experiments, we examine multiple routes by which bacterial cellular components can enter the fetus and the fetal response to influx of bacterial DNA and protein. We inoculated maternal sheep with genetically-labeled S. aureus (Staphylococcus aureus) using three routes: intravenously, orally, and intra-vaginally. The inoculum did not produce sepsis or fever in the ewes, therefore mimicking incidental exposure to bacteria during pregnancy. 3–5 days post inoculation, we assessed the presence of bacterial components in the fetal tissues and analyzed fetal brain tissue to identify any alterations in gene expression. Our results demonstrate that components of bacteria that were introduced into the maternal mouth were detected in the fetal brain and that they stimulated changes in gene expression. We conclude that an oral route of transmission is relevant for transfer of bacterial cellular components to the fetus.

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“…Immune function and types of physiological insults are also explored by Zarate and colleagues, who demonstrate that the nature of a hypoxic stimulus can modify posthypoxic responses by the fetus (Zarate et al . ). Whereas, maternal hypoxic‐hypoxia led to an increase in inflammation mediators and immune cells in the fetal brain transient, partial umbilical cord occlusion producing a similar level of hypoxia did not, but instead modulated genes related to metabolism.…”

mentioning

confidence: 97%