Mice produced by mitotic reprogramming of sperm injected into haploid parthenogenotes.
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 5'-methylcytosine and 5'-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.
Laboratory of Mammalian Molecular Embryology, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
Toru
T
Suzuki
Laboratory of Mammalian Molecular Embryology, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
Maki
M
Asami
Project Group Personalized Tumor Therapy, Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, 93053 Regensburg, Germany.
Martin
M
Hoffmann
Experimental Medicine and Therapy Research, University of Regensburg, 93053 Regensburg, Germany.
Xin
X
Lu
Experimental Medicine and Therapy Research, University of Regensburg, 93053 Regensburg, Germany.
Miodrag
M
Gužvić
Project Group Personalized Tumor Therapy, Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, 93053 Regensburg, Germany.|Experimental Medicine and Therapy Research, University of Regensburg, 93053 Regensburg, Germany.
Christoph A
CA
Klein
Laboratory of Mammalian Molecular Embryology, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
Anthony C F
ACF
Perry
D000818:Animals; D065150:Cellular Reprogramming; D047108:Embryonic Development; D005260:Female; D006238:Haploidy; D008297:Male; D051379:Mice; D008938:Mitosis / Q000502:physiology*; D010312:Parthenogenesis; D011247:Pregnancy; D020554:Sperm Injections, Intracytoplasmic; D013094:Spermatozoa / Q000502:physiology*; D015053:Zygote