NPFF increases fusogenic proteins syncytin 1 and syncytin 2 via GCM1 in first trimester primary human cytotrophoblast cells
Bibliographic record
Abstract
Neuropeptide FF (NPFF) is well-known for its roles in the central nervous system. Despite studies demonstrating that NPFF receptor 2 (NPFFR2) mRNA is highest in placenta, nothing is known about NPFF-NPFFR2 functions in placental development. Here, we investigated the effects of NPFF-NPFFR2 on expression of syncytial [human chorionic gonadotropin (hCG) β] and fusogenic [syncytin 1, syncytin 2, and glial cells missing 1 (GCM1)] genes in first trimester primary human cytotrophoblast cells. By analyzing two publicly available microarray data sets, we found that NPFF is consistently expressed throughout gestation whereas NPFFR2 increases in first trimester and is elevated in placenta samples from women with preeclampsia. Immunohistochemistry showed that NPFFR2, syncytin 1/2, and GCM1 each displayed unique patterns of expression among different trophoblast populations in first trimester placenta. Treatment of primary human cytotrophoblast cells with NPFF increased the mRNA and protein levels of hCG β, syncytin 1, syncytin 2, and GCM1; and knockdown of NPFFR2 abolished these effects. Interestingly, GCM1 mediated NPFF-induced upregulation of syncytin 1 and syncytin 2, but not hCG β, in primary human cytotrophoblasts. Our results demonstrate that NPFF acts via NPFFR2 to enhance production of hCG β and promote GCM1-dependent expression of syncytin 1 and 2 in human cytotrophoblasts.
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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".