Targeting epigenetic nuclear reprogramming in aggregated cloned equine embryos
Thiago V. Damasceno Teixeira A , Richard C. Fry A , Angus McKinnon B , Kerri L. Fry A , Jennifer M. Kelly C , Paul J. Verma C , Chelsie Burden B , Daniel F. Salamone
D E and Andrés Gambini D E F
+ Author Affiliations
- Author Affiliations
A Laboratory of Animal and Meat Sciences, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Grattan Street, Parkville, Victoria, 3010, Australia.
B Goulburn Valley Equine Hospital, 905 Goulburn Valley Highway, Congupna, Victoria 3633, Australia.
C South Australian Research and Development Institute (SARDI), Turretfield Research Centre, Holland Road, Rosedale, 5350, South Australia, Australia.
D Laboratorio de Biotecnología Animal, Facultad de Agronomia, Universidad de Buenos Aires, Av. San Martin 4453, C1417DSE, Ciudad Autónoma de Buenos Aires, Argentina.
E Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz 2290, C1425FQB, Ciudad Autónoma de Buenos Aires, Argentina.
F Corresponding author. Email: gambini@agro.uba.ar
Reproduction, Fertility and Development 31(12) 1885-1893 https://doi.org/10.1071/RD19239
Submitted: 27 June 2019 Accepted: 10 August 2019 Published: 4 October 2019
Abstract
Epigenetic perturbations during the reprogramming process have been described as the primary cause of the low efficiency of somatic cell nuclear transfer (SCNT). In this study, we tested three strategies targeting nuclear reprogramming to investigate effects on equine SCNT. First, we evaluated the effect of treating somatic cells with chetomin, a fungal secondary metabolite reported to inhibit the trimethylation on histone 3 lysine 9 (H3K9 me3). Second, caffeine was added to the culture medium during the enucleation of oocytes and before activation of reconstructed embryos as a protein phosphatase inhibitor to improve nuclear reprogramming. Third, we tested the effects of the histone deacetylase inhibitor trichostatin A (TSA) added during both activation and early embryo culture. Although none of these treatments significantly improved the developmental rates of the in vitro aggregated cloned equine embryos, the first equine cloned foal born in Australia was produced with somatic cells treated with chetomin. The present study describes the use of chetomin, caffeine and TSA for the first time in horses, serving as a starting point for the establishment of future protocols to target epigenetic reprogramming for improving the efficiency of equine cloning. Cloning is an expensive and inefficient process, but has gained particular interest in the equine industry. In this study we explored different strategies to improve cloning efficiency and produced the first cloned foal born in Australia. Our data serve as a starting point for the establishment of future protocols for improving equine cloning efficiency.
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