Trophoblast-Specific Reduction of VEGFA Alters Placental Gene Expression and Maternal Cardiovascular Function in Mice1
Bibliographic record
Abstract
Given the angiogenic function of vascular endothelial growth factor A (VEGFA), the function of its expression by trophoblast in the avascular placental junctional zone is unknown. In mice, cells from the trophoblast-specific protein alpha (Tpbpa) lineage populate this zone and, in late gestation, some of these cells invade the decidual layer. To diminish Vegfa expression in Tpbpa cells, we crossed Vegfa(flox/flox) females with males carrying Tpbpa-Cre. For single deletion (sd) of Vegfa in Tpbpa cells in 100% of conceptuses (SD100 pregnancies, sd conceptuses) we crossed homozygous lines. For double deletion (dd) of both Vegfa alleles in 50% of the conceptuses (DD50 pregnancies, 50% dd conceptuses and 50% no deletion [nd]), we crossed homozygous Vegfa(flox/flox) females with males heterozygous for Tpbpa-Cre and homozygous for Vegfa(flox/flox). Controls were Vegfa(flox/flox) females bred to wild-type males (V-CTRL pregnancies). In SD100 pregnancies, maternal plasma immunoreactive VEGFA significantly increased and arterial blood pressure decreased, whereas fetal body weight and placental Flt1, sFlt1, and Prl3b1 mRNA were unchanged. In DD50, maternal immunoreactive VEGFA and arterial pressures were unaltered, but both dd and nd conceptuses exhibited significantly increased embryonic lethality, altered expression of Flt1, sFlt1, and Prl3b1 mRNA in the decidual layer, and decreased fetal body weight relative to V-CTRL. Maternal cardiac output significantly increased in proportion to dd conceptuses in the pregnancy. In DD50, results are consistent with altered maternal function beginning in early gestation and adversely impacting both conceptus genotypes. We conclude that maternal function is influenced by Vegfa expression in trophoblast cells at the maternal-fetal interface, likely via an endocrine mechanism.
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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".