Nodal and cripto-1: distinct functions regulate trophoblast specification in mouse pregnancy
Bibliographic record
Abstract
Introduction Proper placentation is essential for fetal growth and development in mammals. Nodal signaling is essential to ensure proper embryo development and requires Cripto-1 as a co-receptor. Both factors have been shown to be expressed in the maternal decidua and developing placenta. Notably, a maternal loss of either Nodal or Cripto-1 leads to defective placentation resulting in intrauterine growth restriction and fetal loss. However, the role of Nodal or Cripto-1 in placental development has not been determined. Methods To better understand the roles of Nodal and Cripto-1 in trophoblast populations, we employed a trophoblast-specific deletion model using Tat-Cre recombinant protein to induce deletion of the floxed Nodal or Cripto-1 genes exclusively in the trophectoderm at the blastocyst stage (TE-KO). Treated embryos were then transferred into the uteri of pseudopregnant mice, and implantation sites were examined at gestational days (d) 8.5 and 10.5. Placental morphology and trophoblast populations were analyzed through histological and molecular marker analysis. Results TE-KO of Nodal led to a decrease in the implantation site size and placental thickness, primarily due to a smaller labyrinth area while the junctional zone was increased. Immunostaining revealed an important expansion of PL+ trophoblast giant cells and decrease of TPBPA+ spongiotrophoblast/glycogen cells. TE-KO of Cripto-1 also led to smaller implantation sites and reduced placental thickness, but this was attributed to a smaller junctional zone. A decrease in TPBPA+ spongiotrophoblast cells without affecting Pcdh12+ glycogen cells was observed. A reduction in MCT1+ and Gcm1+ syncytiotrophoblasts and an increase in total area of maternal blood sinuses within the labyrinth emphasized its disorganization. Earlier effects of Cripto-1 TE-KO on the trophoblast maintenance were witnessed at d8.5, with a marked reduction in TPBPA+ cells, reduced trophoblast cell proliferation (PCNA+) and increased apoptosis (TUNEL+). Discussion The distinct phenotypes observed indicate the different roles Nodal and Cripto-1 play in placental development. This highlights the importance of other TGF-β-dependent and independent pathways involving Cripto-1. Overall, our findings highlight the critical role of Nodal and Cripto-1 in regulating key aspects of placental development, including trophoblast differentiation, cellular specification, and structural organization, promising avenues for future research in placental biology.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".