<i>Ex vivo</i> Analysis of Chorioallantoic Fusion Shows that TMED2 is Required in the Chorion for Normal Placental Development
Bibliographic record
Abstract
Development of the labyrinth layer of the mouse placenta proceeds rapidly after a process called chorioallantoic fusion. As a consequence of chorioallantoic fusion the chorion and allantois attach and a subset of chorionic trophoblast cells differentiate into syncytiotrophoblast. Chorioallantoic fusion and subsequent events remains poorly described, partly due to difficulties in ex vivo analysis of the placenta. We report conditions for ex vivo culture of the developing murine placenta and preliminary analysis of placental development in Tmed2 homozygous mutant embryos. Anti‐mesometrial halves of decidua containing pre‐attachment chorions were cultured alone or with explants of allantoides from stage‐matched embryos. Histology, confocal and immunofluorescence microscopy were used for morphological analysis. In situ hybridization and qRT‐PCR were used for molecular analysis. Wildtype Explants cultured without an allantois proliferated with no morphological or molecular initiation of labyrinth layer formation. However, chorions of wildtype explants from eGFP positive embryos co‐cultured with stage‐matched wildtype allantoides from eGFP negative embryos or vice versa remained associated, with rare mixing of eGFP positive and negative cells after 12 hours of culture. By 24 hours, a mosaic pattern of eGFP positive and negative cells was found, with increased proliferation in the allantoic region and branching morphogenesis in the chorionic region. In addition, although expression of the syncytiotrophoblast (SynT) cell type‐II marker Gcm1 increased over culture time, expression of the SynT‐I marker, Syncytin A, decreased and expression of the spongiotrophoblast cell marker Tpbp α was only maintained in explants co‐cultured with an allantois. Recombination of Tmed2 homozygous mutant explants from eGFP positive embryos with wildtype allantoides of eGFP negative embryos, and vice versa, suggest that Tmed2 is required in the chorion for initiation of trophoblast differentiation. In addition, increased cell death was found in tissues from Tmed2 homozygous mutant embryos. Our data show that chorioallantoic fusion and events associated with initiation of labyrinth layer formation can be modeled ex vivo, and reveal a previously unsuspected requirement for chorioallantoic fusion for Tpbpα expression. Our data further suggest that TMED2 is required cell‐autonomously in he chorion for Trophoblast differentiation and cell survival. Support or Funding Information NSERC grant number 214976
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".