Differential changes in trophoblast lineage allocation in rats deficient in uterine natural killer cells
Bibliographic record
Abstract
Uterine natural killer (uNK) cells are the most prevalent uterine leukocyte population during early pregnancy. They are recruited to the uterus soon after embryo implantation, and “prime” the uterine spiral arteries in preparation for the increased demand on these vessels later in pregnancy. A second wave of spiral artery modification occurs by invasive trophoblast cells. Invasive trophoblast cells originate in a specialized compartment of the placenta ‐ called the junctional zone in rodents ‐ and progressively migrate into the uterus en route to the spiral arteries. This “two‐wave” transformation of the uterine vasculature by both NK cells and trophoblast cells occurs in humans and rats. The purpose of this study was to generate and characterize a genetic model of uNK cell deficiency in rats, and observe the resulting consequences on trophoblast development and reproductive outcomes. To accomplish this task, we utilized zinc finger nuclease (ZFN)‐mediated genome editing of the interleukin 15 ( Il15 ) gene. The Il15 locus was targeted because it encodes a cytokine required for NK cell maturation and survival. ZFNs were microinjected into zygotes, and transferred to pseudopregnant dams. Following genotypic characterization of pups, we identified a founder animal containing a seven base‐pair deletion within exon 2 of the Il15 locus. The deletion resulted in a frame shift within the coding sequence of Il15 , and caused a functional loss of IL15 protein. In comparison to wild‐type pregnant female rats, whose uteri contained massive quantities of perforin‐positive NK cells, uteri of females harboring a homozygous mutation at the Il15 locus contained no detectable uNK cells. At midgestation, an expansion of the junctional zone of the placenta was observed, as well as depth and quantity of trophoblast cells invading within the spiral arteries. Accordingly, the internal luminal diameters of these vessels were substantially larger in rats lacking uNK cells. In summary, we demonstrate here significant differences in the size of the junctional zone and the number of invasive trophoblast cells in uNK cell‐deficient rats. These studies will enhance our understanding of the role of NK cells on uterine spiral artery remodeling, trophoblast invasion, and hemochorial placental development. Support or Funding Information Supported by NIH HD020676
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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 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".