Single-cell multiomics sequencing reveals the reprogramming defects in embryos generated by round spermatid injection

Area of Science:

• Reproductive biology
• Epigenetics
• Developmental biology

Background:

• Round spermatid injection (ROSI) is a promising technique for treating male infertility.
• The clinical application of ROSI is limited by the compromised developmental potential of ROSI embryos.
• The underlying mechanisms for this developmental defect are not fully understood.

Purpose of the Study:

• To investigate the reprogramming defects in mouse ROSI embryos using single-cell multiomics.
• To identify potential therapeutic strategies to improve ROSI embryo development.

Main Methods:

• Single-cell multiomics sequencing (transcriptome, chromatin accessibility, DNA methylation) of mouse ROSI embryos.
• Screening of small compounds to identify those that enhance ROSI embryo development.

Main Results:

• Identified reprogramming defects in ROSI embryos at the pronuclear stage, linked to misexpression of zygotic genome activation genes.
• Discovered that compound A366 significantly enhances ROSI embryo developmental potential.
• Demonstrated that A366 partially corrects reprogramming defects by modulating epigenetic and transcriptomic states.

Conclusions:

• Uncovered key reprogramming defects in ROSI embryos, providing insights into their compromised developmental potential.
• Compound A366 offers a potential therapeutic avenue for optimizing the ROSI technique.
• This study advances the understanding of early embryonic development and infertility treatments.