Hypoxia in extravillous trophoblasts links maternal obesity and offspring neurobehavior
Bibliographic record
Abstract
While maternal obesity (MO) is associated with neurobehavioral impairment (NBI) in offspring, the underlying mechanisms remain unknown. The placenta is thought to play a role in fetal programming. To elucidate the association between MO and offspring NBI, we performed single-nucleus RNA-seq on maternal- and fetal-facing sides of human term placentas from MO and lean groups. MO placentas showed the upregulation of hypoxia response genes in multiple cell types, and maternal-facing hypoxia gene expression correlated with offspring NBI in an independent birth cohort, Gen3G. Extravillous trophoblasts (EVTs) showed the highest expression of NBI-correlated genes, and EVT NBI-gene expression correlated with hypoxia signatures in two cohorts. Exposing cultured EVTs to hypoxia increased NBI gene expression, and 44% of the association between maternal BMI and NBI-gene expression in EVTs was mediated by hypoxia. Our findings suggest that hypoxia in EVTs is a key process in the neurodevelopmental programming of fetal exposure to MO.
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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".