Mice produced by mitotic reprogramming of sperm injected into haploid parthenogenotes

Toru Suzuki, Maki Asami, Martin Hoffmann, Xin Lu, Miodrag Guzˇvic´, Christoph A. Klein & Anthony C.F. Perry

Nat. Commun. 7:12676 doi:10.1038/ncomms12676 (2016)

Sperm are highly differentiated and the activities that reprogram them for embryonic development during fertilization have historically been considered unique to the oocyte.

We here challenge this view and demonstrate that mouse embryos in the mitotic cell cycle can also directly reprogram sperm for full-term development. Developmentally incompetent haploid embryos (parthenogenotes) injected with sperm developed to produce healthy offspring at up to 24% of control rates, depending when in the embryonic cell cycle injection took place. This implies that most of the first embryonic cell cycle can be bypassed in sperm genome reprogramming for full development. Remodelling of histones and genomic 50-methylcytosine and 50-hydroxymethylcytosine following embryo injection were distinct from remodelling in fertilization and the resulting 2-cell embryos consistently possessed abnormal transcriptomes. These studies demonstrate plasticity in the reprogramming of terminally differentiated sperm nuclei and suggest that different epigenetic pathways or kinetics can establish totipotency.

A two cell embryo created using phICSI.

Fluorescence image (BrdU, maternal genome; PI, both genomes) show 2+1 class of nuclear configuration 14h after the first mitotic division (1C --> 2C) in phICSI-13 embryo.

White arrowhead: paternal chromatin.