Determining the Role of Natural Killer Cells in Immune‐Mediated Fetal Growth Restriction in Rats
Bibliographic record
Abstract
Pregnancy is a unique state in which two genetically foreign individuals – mother and fetus – coexist in immunological harmony. The mechanisms facilitating this immunological tolerance are not well understood; however, the uterus contains a unique population of immune cells belonging to the natural killer (NK) cell lineage that likely have a key role in promoting tolerance. Uterine NK cells are purported to promote uterine vascular remodeling as well as facilitate placental and fetal development during pregnancy. We hypothesize that exposure to pathogenic stimuli early in pregnancy disrupts normal functioning of uterine NK cells, thereby impacting uterine vascular remodeling and fetal growth. To test this hypothesis, the viral mimetic polyinosinic:polycytidylic acid (polyI:C) was injected into pregnant rats under control conditions or following NK cell depletion using anti‐asialo GM1 antibodies, and changes in uterine cytokine production and fetal growth were assessed. Rats were injected with 1, 5, or 10 mg/kg polyI:C on gestational day 8.5, while control rats were injected with saline. Dams injected with 10 mg/kg polyI:C exhibited a 15% decrease in fetal weight and a 4% decrease in fetal crown‐rump length, without affecting fetal viability. Decreased fetal weight correlated with increased production of inflammatory cytokines (interferon‐gamma, tumour necrosis factor‐alpha, and interleukin‐6) in both spleen and implantation sites, and increased perforin expression within implantation sites. Interestingly, immunodepletion of NK cells prior to injection of 10 mg/kg polyI:C resulted in a 38% decrease in fetal weight compared to control animals, indicating that uterine NK cells have a role in preventing fetal growth restriction caused by polyI:C exposure. In conclusion, injection of polyI:C into pregnant rats resulted in elevated cytokine production and fetal growth restriction that was exacerbated by a lack of NK cells. Support or Funding Information Children's Health Research Institute, Preeclampsia Foundation of Canada, Schulich Medicine and Dentistry
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".