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
ABSTRACT Maternal excess adiposity (i.e., overweight and obesity) at conception is linked to numerous signs of malperfusion and inflammatory injury in the placenta. Previous reports have suggested that obesity-associated placental malperfusion may trigger a state of fetoplacental hypoxia, contributing to adverse health outcomes within and beyond the perinatal period. However, many previous studies have relied on indirect measures of tissue oxygen saturation, including readouts influenced by external inflammatory stressors. Direct comparisons of tissue oxygen saturation at the uteroplacental interface in pregnancies complicated by excess adiposity are lacking. Here, we used a mouse model of chronic preconception high-fat, high-sucrose (HFHS) diet feeding to model the impacts of an obesogenic milieu on placental oxygenation near term gestation (E17.5). We found that both placental junctional and labyrinth zone tissues were relatively hypoxic in HFHS pregnancies compared to chow-fed controls (CON). However, this was not associated with enhanced HIF-1α expression in labyrinth tissues. Similarly, placentas from CON and HFHS dams did not exhibit gross differences in morphology or vessel density and pericyte coverage. However, HFHS placentas have 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 within the labyrinth zone proteome, which differed in magnitude with fetal sex. While fetal growth was not markedly affected, fetuses from HFHS pregnancies exhibited higher levels of circulating IL-6, prolactin, CXCL1, and CCL2. Collectively, these data confirm that diet-induced maternal excess adiposity leads to a relative state of placental hypoxia, even in the absence of marked growth restriction or fetal demise. While this hypoxic state is not linked to gross morphological abnormalities, it is associated with a greater histopathological burden indicative of local malperfusion and inflammation, and an altered fetal inflammatory and endocrine milieu in late gestation. These findings provide new insight into mechanisms by which an obesogenic environment during pregnancy compromises placental function and contributes to the long-term programming of chronic disease susceptibility.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".