Fetal brain sparing in a mouse model of chronic maternal hypoxia
Bibliographic record
Abstract
Pregnancy complication may cause acute or chronic hypoxic stress to the fetus. The fetal response to acute hypoxia has been well characterized 1 and is associated with brain sparing, a mechanism by which more oxygenated blood is directed to the brain at the expense of organs such as the liver and the lungs 2–4 . In contrast, the fetal response to chronic hypoxia is not well understood. In the present study, Doppler ultrasound was used to characterize the fetal hemodynamic responses to chronic maternal hypoxia during late gestation in pregnant mice. Pregnant CD‐1 mice were randomly assigned to either a chronic hypoxia (n=13) (11% O 2 from gestational day E14.5 to E17.5) or control (n=13) group. Doppler ultrasound measurements were acquired at E17.5 (full term for CD‐1 dams is E18.5) of the middle cerebral artery, ductus venosus, main pulmonary artery, ductus arteriosus, and the umbilical artery. An acute hypoxic condition (8% O 2 for 3 minutes) was used to challenge the fetus and assess its capacity to compensate for additional hypoxia stress. Fetal organ growth was assessed using ex vivo magnetic resonance imaging (MRI). The fetuses exposed to chronic maternal hypoxia weighed 15% less than controls, indicating that the hypoxia‐exposed fetuses failed to reach their growth potential. Fetal cerebral blood flow was elevated by 31%, ductus venosus blood flow was 69% higher and pulmonary blood flow was decreased by 74% in the fetuses exposed to chronic hypoxia compared to controls. This demonstrates that the brain sparing response persists during chronic fetal hypoxia and is mediated by “streaming”, where highly oxygenated blood preferentially flows through the ductus venosus towards the cerebral circulation, bypassing the liver and the lungs. Consistent with these changes in blood flow, the brain volume is preserved while the lung and liver volumes decreased by 27 and 22% respectively in fetuses exposed to chronic hypoxia compared to controls. With an acute hypoxic challenge, the cerebral and ductus venosus blood flow increased in control fetuses. The elevated flow was achieved by an increased fetal heart rate and vasodilation. In contrast, the blood flow in the fetuses exposed to maternal hypoxia decreased when challenged. The decrease was accompanied by a drop in fetal heart rate, suggesting the fetus can no longer compensate for the decreased oxygen transport across the placenta. This highlights that fetuses exposed to chronic maternal hypoxia are at increased risk of fetal demise caused by an acute episode of hypoxia; for example, those that commonly occur during labour and delivery. Support or Funding Information Funded by Canadian Institutes of Health Research Grant MOP130403.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".