Abstract 138: White AdiposeTissue in the Preeclamptic-Like BPH/5 Mouse Has a Unique Inflammatory Molecular Signature During Early Pregnancy
Bibliographic record
Abstract
Introduction: Preeclampsia (PE) is a hypertensive disease of pregnancy that affects an estimated 8% of women worldwide. The underlying mechanism is unknown; however, maternal obesity increases the risk of PE by 30% and may contribute to increased inflammation seen in preeclamptic mothers. Hypothesis: To better understand the role of white adipose tissue (WAT) signaling on adverse pregnancy outcomes, we used the obese PE-like BPH/5 mouse to test the hypothesis that visceral WAT has an inflammatory phenotype prior to the presentation of the maternal hypertensive syndrome Methods: Visceral WAT adjacent to the reproductive tract (“reproductive WAT”) was harvested from ad libitum fed control C57 and BPH/5 female mice (8 weeks of age) at embryonic day (e) 7.5. RNA was isolated and subjected to Next Generation Sequencing (NGS) using an Illumina platform. DAVID pathway analysis was performed to annotate differentially expressed genes. BPH/5 female mice were calorie restricted by 25% from e0.5 until e7.5 and reproductive WAT was collected for RNA isolation and quantitative real-time PCR. The calorie restriction paradigm has been shown to significantly reduce reproductive WAT accumulation throughout gestation in BPH/5 mice. Results: NGS of e7.5 reproductive WAT revealed 899 genes that were significantly dysregulated in BPH/5 vs C57. DAVID showed upregulation of lipid metabolic processes in both C57 and BPH/5 pregnant reproductive WAT, while 18 inflammation-related pathways were significantly upregulated in reproductive WAT of pregnant BPH/5 mice compared to pregnant C57 (FDR<=5%, adjP<=0.1, FC >=1.5). Quantitative real-time PCR confirmed upregulation of PE- related inflammatory genes, interleukin (IL)-6, IL-15 and Ptgs2, in e7.5 BPH/5 reproductive WAT vs C57 (n=6, p<0.05). Seven days 25% calorie restriction during pregnancy significantly reduced this elevated IL-6 and Ptgs2 mRNA expression in reproductive WAT (n=6, p<0.05) Conclusions: These data show that obese PE-like BPH/5 mice have elevated inflammatory gene expression in reproductive WAT before placenta formation. Further investigations are needed to confirm if the reduction in IL-6 and Ptgs2 in reproductive WAT by calorie restriction improves fetoplacental and maternal outcomes in BPH/5 mice
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 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".