Interaction of gametes with exogenous genes: possible opportunities for incorporation into embryonic genome

The mechanism of incorporation of foreign DNA into newly fertilized eggs is poorly understood. It is not known with certainty if S phase DNA replication is required or if integration could occur at other times of the cell cycle that involve DNA strand breaks, such as chromatin rearrangements. We have investigated DNA strand breaks in mouse eggs and zygotes with a sensitive terminal uridine nucleotide end labeling (TUNEL) assay. Greater than 90% of all polar bodies and metaphase II chromosomes in freshly ovulated mouse eggs are TUNEL-assay positive. Approximately one-third of zygotes assayed 6 hr after fertilization contain at least one TUNEL assay positive pro-nucleus and/or decondensing sperm head. These results indicate that early embryonic DNA contains multiple transient DNA breaks that could play a role in the incorporation of foreign DNA.