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Gonadotropin stimulation contributes to an increased incidence of epimutations in ICSI-derived mice
- Source :
- Human Molecular Genetics. 21:4460-4472
- Publication Year :
- 2012
- Publisher :
- Oxford University Press (OUP), 2012.
-
Abstract
- We previously demonstrated that intracytoplasmic sperm injection (ICSI), a type of assisted reproductive technology (ART), can induce epimutations and/or epimutant phenotypes in somatic tissues of adult mice produced by this method. In the present study, we compared the occurrence of epimutations in mice produced by natural conception, ICSI and somatic cell nuclear transfer. Surprisingly, we observed the highest frequency of epimutations in somatic tissues from ICSI-derived mice. We also observed a delay in reprogramming of the maternal allele of the imprinted H19 gene in spermatogonia from juvenile ICSI-derived male mice. These observations led us to hypothesize that the exposure of the maternal gametic genome to exogenous gonadotropins during the endocrine stimulation of folliculogenesis (superovulation) may contribute to the disruption of the normal epigenetic programming of imprinted loci in somatic tissues and/or epigenetic reprogramming in the germ line of ensuing offspring. To test this hypothesis, we uncoupled superovulation from ICSI by subjecting female mice to gonadotropin stimulation and then allowing them to produce offspring by natural mating. We found that mice produced in this way also exhibited epimutations and/or epimutant phenotypes in somatic tissues and delayed epigenetic reprogramming in spermatogenic cells, providing evidence that gonadotropin stimulation contributes to the induction of epimutations during ART procedures. Our results suggest that gonadotropin stimulation protocols used in conjunction with ART procedures should be optimized to minimize the occurrence of epimutations in offspring produced by these methods.
- Subjects :
- Male
medicine.medical_specialty
medicine.drug_class
Somatic cell
Offspring
Stimulation
Biology
Germline
Epigenesis, Genetic
Genomic Imprinting
Mice
Internal medicine
Genetics
medicine
Animals
Sperm Injections, Intracytoplasmic
Molecular Biology
Alleles
Genetics (clinical)
Articles
General Medicine
Embryo, Mammalian
Mice, Inbred C57BL
Phenotype
Endocrinology
Mutation
Somatic cell nuclear transfer
Female
Gonadotropin
Genomic imprinting
Reprogramming
Gonadotropins
Subjects
Details
- ISSN :
- 14602083 and 09646906
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Human Molecular Genetics
- Accession number :
- edsair.doi.dedup.....f686cc6d8dc903a41f9945d7a970d59b