Altered expression of ADM and ADM2 by hypoxia regulates migration of trophoblast and HLA-G expression†
Bibliographic record
Abstract
Preeclampsia (PE) is a placental disorder caused by endothelial dysfunction via trophoblast inadequate invasion activity. Adrenomedullin (ADM) and ADM2 are multifunctional peptides that can support vascular activity and placental growth. However, correlation between ADMs and trophoblast functions is currently unclear. The objective of this study was to analyze changes in expression of ADMs in placenta and HTR-8/SVneo trophoblast cells under hypoxia and their effects on invasion activity of trophoblast cells and expression of HLA-G. In placental tissues of PE, expression levels of ADM and HLA-G were significantly increased (P < 0.05) whereas expression of ADM2 was decreased compared to that in normal term placenta. Under hypoxia, expression levels of ADM, ADM2, and HLA-G and invasion ability of trophoblast cells were increased in hypoxia-inducible factor-1 (HIF-1α)- dependent manner (P < 0.05). Treatment with ADMs agonists reduced HIF-1α activity whereas enhanced invasion ability under hypoxia. However, they were not changed after cotreatment of ADMs and HIF-1α inhibitor, YC-1, although expression levels of invasion-related genes MMP2, MMP9, and Rac1 were altered (P < 0.05). ADMs also increased HLA-G expression under normoxia whereasADM2 or cotreatment of ADMs under hypoxia attenuated HLA-G expression (P < 0.05). Our findings demonstrate that altered expression of ADMs plays a critical role in placental physiology, especially in trophoblast invasion and immune-modulation under hypoxia.
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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".