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

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-ICSIproduced 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) DFSICSI affects the postnatal expression of a defined epigenetically sensitive allele and this modification may be inherited across generations. © 2014 Ramos-Ibeas et al.

Bibliographic Details

Main Authors:	Ramos Ibeas, Priscila, Calle, A., Fernández González, Raúl, Laguna-Barraza, R., Pericuesta Camacho, Eva, Calero Prieto, Antonia, Ramírez De Paz, Miguel Ángel, Gutiérrez Adán, Alfonso
Format:	artículo biblioteca
Language:	English
Published:	Public Library of Science 2014
Online Access:	http://hdl.handle.net/20.500.12792/3653 http://hdl.handle.net/10261/290554
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