A temporal extracellular transcriptome atlas of human pre-implantation development

Area of Science:

• Reproductive Biology
• Genomics
• Biochemistry

Background:

• Non-invasive assessment of gene expression in human pre-implantation embryos is challenging.
• Extracellular RNAs (exRNAs) in spent culture media offer a potential source of information.

Purpose of the Study:

• To develop a non-invasive method for comprehensive characterization of exRNAs in human pre-implantation embryos.
• To create a temporal extracellular transcriptome atlas (TETA) for human pre-implantation development.
• To identify exRNA signatures associated with embryo developmental arrest and quality.

Main Methods:

• Collected spent media from human in vitro fertilization embryos across five developmental stages.
• Performed exRNA sequencing on single droplet samples.
• Generated the Temporal Extracellular Transcriptome Atlas (TETA) with 245 datasets.
• Utilized machine learning to correlate exRNA levels with embryo morphology-based ratings.

Main Results:

• Identified approximately 4,000 exRNAs at each developmental stage.
• Found exRNAs in arrested embryos were enriched with genes regulating cell cycle, indicating a developmental arrest signature.
• Developed a machine-learning model that predicts embryo quality from exRNA levels.
• Demonstrated widespread presence of coding gene-derived exRNAs throughout pre-implantation development.

Conclusions:

• The developed non-invasive method enables comprehensive exRNA profiling of human pre-implantation embryos.
• Extracellular RNAs provide valuable insights into embryo physiology, developmental arrest, and quality assessment.
• TETA serves as a foundational resource for understanding the extracellular transcriptome in early human development.