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Updated: Oct 26, 2025
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Protocol for Human Blastoids Modeling Blastocyst Development and Implantation
Published on: August 10, 2022
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Blastocyst trophectoderm endocytic activation, a marker of adverse developmental programming
Laura Caetano1, Judith J Eckert2, David Johnston3
1Biological Sciences, Southampton General Hospital, University of Southampton, Southampton, UK.
Reproduction (Cambridge, England)
|August 2, 2021
Summary
Maternal low protein diet impacts embryo development. Isoleucine deficiency activates nutrient uptake pathways in mouse and human blastocysts, mediated by TFEB, potentially serving as an early health biomarker.
Area of Science:
- Developmental Biology
- Reproductive Biology
- Cell Biology
Background:
- Maternal dietary protein restriction affects embryo development and long-term health.
- Low-protein diet (LPD) reduces blastocyst mTORC1 signaling and branched-chain amino acid (BCAA) availability.
- BCAA deficiency induces compensatory nutrient uptake mechanisms in the trophectoderm (TE).
Purpose of the Study:
- Investigate the mechanism of TE responsiveness to individual BCAA variations.
- Identify the transcription factor mediating the histotrophic response.
- Determine if similar mechanisms are present in human blastocysts related to maternal nutritional status.
Main Methods:
- In vitro quantitative model of TE responsiveness to BCAA deficiency.
- Analysis of endocytosis, lysosome biogenesis, and TFEB translocation.
- Examination of human blastocysts from women with varying body mass index.
Main Results:
- Isoleucine (ILE) deficiency most effectively activated TE endocytosis and lysosome biogenesis.
- TE response to low ILE involved megalin receptor and cathepsin-B upregulation, starting from blastocyst formation.
- TFEB mediated the histotrophic response via nuclear translocation during ILE deficiency and mTORC1 inhibition.
- Human blastocysts from women with high BMI showed stimulated lysosome biogenesis and TFEB nuclear migration.
Conclusions:
- TE lysosomal phenotype is a sensitive indicator of nutrient stress during preimplantation development.
- TFEB-mediated lysosome biogenesis is a conserved response to nutrient scarcity.
- This lysosomal phenotype may serve as an early biomarker for potential long-term health outcomes associated with environmental nutrient stress.
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