Evaluate the developmental competence of human 8-cell embryos by single-cell RNA sequencing

Area of Science:

• Developmental Biology
• Reproductive Medicine
• Genomics

Background:

• Human preimplantation embryo development hinges on the critical transition from maternal to zygotic gene expression regulation.
• Infertility affects many females due to unexplained early embryonic developmental failures.
• The 8-cell stage is crucial for the onset of embryonic gene expression.

Purpose of the Study:

• To evaluate transcriptomes in single blastomeres from human 8-cell embryos using single-cell RNA sequencing (scRNA-seq).
• To determine associations between gene expression profiles and developmental competence of early human embryos.
• To identify potential biomarkers for predicting embryo development and therapeutic targets for assisted reproductive technologies (ART).

Main Methods:

• Blastomeres were biopsied from 8-cell embryos of patients undergoing ART.
• scRNA-seq was employed to analyze gene expression at the single-cell level.
• Gene expression data was correlated with subsequent embryo development outcomes (blastocyst formation).

Main Results:

• Reduced overall gene detection in 8-cell embryos that failed to form blastocysts.
• Identification of 324 differentially expressed genes, with 65 significantly suppressed in non-competent embryos.
• Suppressed genes are associated with cell cycle, DNA transcription, histone methylation, and cell division, including SMCO-1, ZNF271P, ZNF679, ASF1b, BEX3, DPPA2, and ORC4.

Conclusions:

• Gene expression alterations in human 8-cell embryos are tightly linked to their developmental competence.
• Specific suppressed genes in arrested embryos point to underlying molecular dysfunctions.
• These findings offer potential targets for enhancing embryo development and predictive parameters for ART success.