Maternal high-fat, high-sucrose diet–induced excess adiposity is linked to placental hypoxia and disruption of fetoplacental immune homeostasis in late gestation
Bibliographic record
Abstract
Maternal excess adiposity during pregnancy is linked to placental malperfusion and inflammatory injury. Obesity-associated placental malperfusion may induce fetoplacental hypoxia, contributing to adverse health outcomes within and beyond the perinatal period. However, direct comparisons of tissue oxygen saturation at the uteroplacental interface in pregnancies complicated by excess adiposity are lacking. Using a mouse model of preconception high-fat, high-sucrose (HFHS) diet-induced excess adiposity, we found that both placental junctional and labyrinth zones at E17.5 were hypoxic compared to chow-fed controls (CON). HFHS placentas had a greater burden of histopathological lesions, including tissue calcification and fibrinoid deposition within the labyrinth zone. Calcified placental tissue coincided with the destruction of vasculosyncytial membranes and macrophage-dense foci, alongside altered expression of immunomodulatory and chemotactic cytokines, which differed in magnitude with fetal sex. While fetal growth was not impaired, fetuses from HFHS pregnancies exhibited higher levels of circulating IL-6, prolactin, CXCL1, and CCL2. Collectively, these data confirm that maternal diet-induced excess adiposity leads to a reduction in placental oxygen saturation, even in the absence of marked growth restriction or fetal demise. While this hypoxic state was not linked to gross morphological abnormalities, it was associated with markers indicative of local malperfusion and inflammation, and an altered fetal inflammatory and endocrine milieu in late gestation. Together, these findings demonstrate that a state of placental hypoxia may contribute to the increased risk of adverse perinatal outcomes and long-term disease programming in pregnancies affected by maternal obesity.
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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".