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Updated: Jun 23, 2025

Protocol for Human Blastoids Modeling Blastocyst Development and Implantation
Published on: August 10, 2022
Human trophectoderm becomes multi-layered by internalization at the polar region
Elena Corujo-Simon1, Lawrence Edward Bates1, Ayaka Yanagida1
1Wellcome - MRC Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge CB2 0AW, UK.
Human blastocysts show multi-layered polar trophectoderm (TE) before uterine implantation, a crucial step for placental development. Inner TE cells originate from outer TE cells, not the inner cell mass (ICM).
Area of Science:
- Developmental Biology
- Reproductive Science
- Cell Biology
Background:
- Mammalian embryos develop into blastocysts with trophectoderm (TE) and inner cell mass (ICM) for uterine implantation.
- Implantation strategies differ significantly between species, such as mice and humans.
- Human blastocysts attach directly to the uterine wall via polar TE.
Purpose of the Study:
- To investigate the cellular structure of human polar TE before implantation.
- To determine the origin of inner TE cells in human blastocysts.
- To understand early human embryonic development and placental formation.
Main Methods:
- Immunofluorescence (IF) of isolated inner cell masses (ICMs).
- Blockade of RNA and protein synthesis in whole embryos.
- 3D visualization of immunostained embryos.
- Sequential fluorescent labeling of blastocyst cells.
Main Results:
- Evidence of multi-layering in human polar TE prior to uterine implantation.
- The majority of inner TE cells in human blastocysts originate from existing outer TE cells.
- No conversion of inner cell mass (ICM) cells to TE was observed in intact human embryos.
Conclusions:
- Multi-layering of human polar TE may facilitate rapid uterine invasion and placental initiation.
- The TE layer in human blastocysts is established through self-renewal of outer TE cells.
- This study clarifies a key difference in early human embryonic development compared to other mammals.
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