Epigenetic abnormalities
of the mouse paternal zygotic genome associated with microinsemination
of round spermatids
Kishigami S, Van Thuan N, Hikichi T, Ohta H, Wakayama S, Mizutani E and
Wakayama T
Dev Biol 289(1):195-205 (2006)
SUMMARY
Although round spermatid injection can be used to create progeny for males
who do not produce mature sperm, the rate of successful embryogenesis
after such procedures is significantly lower than that for similar procedures
using mature spermatozoa. The mechanisms underlying this difference are
unknown. In this study, we demonstrate that, unlike the normal paternal
genome, the paternal zygotic genome derived from a round spermatid is
highly remethylated before first mitosis after demethylation. Genomes
from elongated spermatids exhibited an intermediate level of DNA methylation,
between those of round spermatids and mature spermatozoa, suggesting that
the male germ cell acquires the ability to maintain its undermethylated
state in the paternal zygotic genome during this phase of spermiogenesis.
In addition, treatment of zygotes with trichostatin A led to a significant
reduction in DNA methylation, specifically in the spermatid-derived paternal
genome, except for the pericentromeric regions enriched by trimethylation
of Lys9 of histone H3. These data provide insight into epigenetic errors
that may be associated with the poor development of embryos generated
from immature spermatozoa.
LINK
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16325170