Aneuploidy during the onset of mouse embryo development

Area of Science:

• Reproductive Biology
• Developmental Biology
• Genetics

Background:

• Aneuploidy is a primary driver of early embryonic arrest in mammals.
• Current understanding of aneuploidy frequency during early development is limited, often relying on indirect measures like micronuclei.
• The mouse model is crucial for studying aneuploidy, but comprehensive data across early developmental stages is lacking.

Purpose of the Study:

• To systematically quantify the frequency of numerical chromosomal aberrations in mouse embryos from zygote to the 16-cell stage.
• To investigate the developmental fate of aneuploid blastomeres and embryos in vivo.
• To understand the impact of aneuploidy on early embryonic cell cycle progression and viability.

Main Methods:

• Systematic scoring of aneuploidy using a kinetochore counting assay in in vivo mouse embryos.
• Analysis of aneuploidy frequency per blastomere and per embryo across developmental stages (zygote to 16-cell).
• Experiments with reconstituted embryos to assess the survival and cell cycle behavior of hyperploid blastomeres.

Main Results:

• Aneuploidy frequency per blastomere is stable from zygote to 8-cell stage, increasing significantly by the 16-cell stage.
• Aneuploidy present in zygotes and 2-cell stage embryos does not typically propagate to later stages, indicating early elimination.
• Hyperploid blastomeres can survive early development but exhibit delayed cell cycle progression, DNA fragmentation, and cell cycle arrest.

Conclusions:

• Aneuploidy frequency increases during early mouse embryonic development, particularly by the 16-cell stage.
• Mechanisms exist to eliminate aneuploid embryos at very early stages (zygote/2-cell).
• While some aneuploid cells survive, they face significant developmental challenges, impacting overall embryo viability.