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Intracytoplasmic sperm injection using DNA-fragmented sperm in mice negatively affects embryo-derived embryonic stem cells, reduces the fertility of male offspring and induces heritable changes in epialleles.


ABSTRACT:

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Intracytoplasmic sperm injection (ICSI) in mice using DNA-fragmented sperm (DFS) has been linked to an increased risk of genetic and epigenetic abnormalities both in embryos and offspring. This study examines: whether embryonic stem cells (ESCs) derived from DFS-ICSI embryos reflect the abnormalities observed in the DFS-ICSI progeny; the effect of DFS-ICSI on male fertility; and whether DFS-ICSI induces epigenetic changes that lead to a modified heritable phenotype. DFS-ICSI-produced embryos showed a low potential to generate ESC lines. However, these lines had normal karyotype accompanied by early gene expression alterations, though a normal expression pattern was observed after several passages. The fertility of males in the DFS-ICSI and control groups was compared by mating test. Sperm quantity, vaginal plug and pregnancy rates were significantly lower for the DFS-ICSI-produced males compared to in vivo-produced mice, while the number of females showing resorptions was higher. The epigenetic effects of DFS-ICSI were assessed by analyzing the phenotype rendered by the Axin1Fu allele, a locus that is highly sensitive to epigenetic perturbations. Oocytes were injected with spermatozoa from Axin1Fu/+ mice and the DFS-ICSI-generated embryos were transferred to females. A significantly higher proportion of pups expressed the active kinky-tail epiallele in the DFS-ICSI group than the controls.

In conclusion

1) ESCs cannot be used as a model of DFS-ICSI; 2) DFS-ICSI reduces sperm production and fertility in the male progeny; and 3) DFS-ICSI affects the postnatal expression of a defined epigenetically sensitive allele and this modification may be inherited across generations.

SUBMITTER: Ramos-Ibeas P 

PROVIDER: S-EPMC3990723 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Intracytoplasmic sperm injection using DNA-fragmented sperm in mice negatively affects embryo-derived embryonic stem cells, reduces the fertility of male offspring and induces heritable changes in epialleles.

Ramos-Ibeas Priscila P   Calle Alexandra A   Fernández-González Raúl R   Laguna-Barraza Ricardo R   Pericuesta Eva E   Calero Antonia A   Ramírez Miguel Ángel MÁ   Gutiérrez-Adán Alfonso A  

PloS one 20140417 4


<h4>Unlabelled</h4>Intracytoplasmic sperm injection (ICSI) in mice using DNA-fragmented sperm (DFS) has been linked to an increased risk of genetic and epigenetic abnormalities both in embryos and offspring. This study examines: whether embryonic stem cells (ESCs) derived from DFS-ICSI embryos reflect the abnormalities observed in the DFS-ICSI progeny; the effect of DFS-ICSI on male fertility; and whether DFS-ICSI induces epigenetic changes that lead to a modified heritable phenotype. DFS-ICSI-p  ...[more]

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