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Primary epimutations introduced during intracytoplasmic sperm injection (ICSI) are corrected by germline-specific epigenetic reprogramming
- Source :
- Proceedings of the National Academy of Sciences of the United States of America. 109(11)
- Publication Year :
- 2012
-
Abstract
- The use of assisted reproductive technologies (ART) has become increasingly common worldwide and is now responsible for 2–3% of children born in developed countries. Multiple reports have suggested that ART-conceived children are more likely to develop rare epigenetic disorders such as Beckwith-Wiedemann Syndrome or Angelman Syndrome, both of which involve dysregulation of imprinted genes. Anecdotal reports suggest that animals produced with ART that manifest apparent epigenetic defects typically do not transmit these epimutations to subsequent generations when allowed to breed naturally, but this hypothesis has not been directly studied. We analyzed allele-specific DNA methylation and expression at three imprinted genes, H19, Snrpn, and Peg3 , in somatic cells from adult mice generated with the use of intracytoplasmic sperm injection (ICSI), a type of ART. Epimutations were detected in most of the ICSI-derived mice, but not in somatic cells of their offspring produced by natural mating. We examined germ cells from the ICSI mice that exhibited epimutations in their somatic cells and confirmed normal epigenetic reprogramming of the three imprinted genes analyzed. Collectively, these results confirm that ART procedures can lead to the formation of primary epimutations, but while such epimutations are likely to be maintained indefinitely in somatic cells of the ART-derived individuals, they are normally corrected in the germ line by epigenetic reprogramming and thus, not propagated to subsequent generations.
- Subjects :
- Male
Somatic cell
medicine.medical_treatment
Reproductive technology
Biology
Intracytoplasmic sperm injection
Germline
Epigenesis, Genetic
Genomic Imprinting
Mice
medicine
Animals
Epigenetics
Sperm Injections, Intracytoplasmic
Alleles
Genetics
Multidisciplinary
Reproduction
DNA Methylation
Biological Sciences
Cellular Reprogramming
Mice, Inbred C57BL
Germ Cells
DNA methylation
Mutation
Female
Genomic imprinting
Reprogramming
Subjects
Details
- ISSN :
- 10916490
- Volume :
- 109
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Accession number :
- edsair.doi.dedup.....88bff28b63f0310235e73e7fab496c89