Intermittent hypoxia impairs uterine artery function in pregnant mice
Bibliographic record
Abstract
Key points Obstructive sleep apnoea (OSA) is a chronic condition characterized by intermittent hypoxia that induces oxidative stress and inflammation leading to cardiovascular disease. Women can develop OSA during late pregnancy, which is associated with adverse maternal and fetal outcomes. However, the effects of OSA throughout pregnancy on fetoplacental outcomes are unknown. Using a mouse model of intermittent hypoxia, we evaluated main uterine artery function, spiral artery remodelling, circulating angiogenic and anti‐angiogenic factors, and placental hypoxia and oxidative stress at gestational day 14.5 in pregnant mice. Gestational intermittent hypoxia increased placental weight but decreased fetal weight, impaired uterine artery function, increased circulating angiogenic and anti‐angiogenic factors, and induced placental hypoxia and oxidative stress, but had no impact on spiral artery remodelling. Our results suggest that pregnant women experiencing OSA during pregnancy could be at risk of maternal and fetal complications. Abstract Obstructive sleep apnoea (OSA) is characterized by chronic intermittent hypoxia (IH) and is associated with increased inflammation, oxidative stress and endothelial dysfunction. OSA is a common sleep disorder and remains under‐diagnosed; it can increase the risk of adverse maternal and fetal outcomes in pregnant women. We investigated the effects of gestational IH (GIH) on uterine artery function, spiral artery remodelling and placental circulating angiogenic and anti‐angiogenic factors in pregnant female mice. WT C57BL/6 mice (8 weeks) were exposed to either GIH ( 12%) or intermittent air ( 21%) for 14.5 days of gestation. Exposure to GIH reduced fetal weight but increased placental weight. GIH dams had higher plasma levels of oxidative stress (8‐isoprostane) and inflammatory markers (tumour necrosis factor‐α). GIH significantly reduced uterine artery function as indicated by reduced endothelium‐dependent vasodilatation and enhanced vasoconstriction. Plasma levels of placental angiogenic and anti‐angiogenic markers (soluble fms‐like tyrosine kinase‐1, soluble endoglin, angiogenic placental growth factor‐2 and vascular endothelial growth factor) were higher in pregnant mice exposed to GIH. There was no evidence of impaired spiral artery remodelling based on immunostaining with α‐smooth muscle actin and cytokeratin‐7, and also by measurements of lumen area. Immunostaining for markers of hypoxia (pimonidazole) and oxidative stress (4‐hydroxynonenal) were higher in mice exposed to GIH. Our data show that GIH adversely affects uterine vascular function and may be a mechanism by which gestational OSA leads to adverse maternal and fetal outcomes.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".