Overexpression of <i>Tet3</i> in donor cells enhances goat somatic cell nuclear transfer efficiency

<jats:p>Ten–eleven translocation 3 (<jats:styled-content style="fixed-case">TET</jats:styled-content>3) mediates active <jats:styled-content style="fixed-case">DNA</jats:styled-content> demethylation of paternal genomes during mouse embryonic development. However, the mechanism of <jats:styled-content style="fixed-case">DNA</jats:styled-content> demethylation in goat embryos remains unknown. In addition, aberrant <jats:styled-content style="fixed-case">DNA</jats:styled-content> methylation reprogramming prevalently occurs in embryos cloned by somatic cell nuclear transfer (<jats:styled-content style="fixed-case">SCNT</jats:styled-content>). In this study, we reported that <jats:styled-content style="fixed-case">TET</jats:styled-content>3 is a key factor in <jats:styled-content style="fixed-case">DNA</jats:styled-content> demethylation in goat pre‐implantation embryos. Knockdown of <jats:italic>Tet3</jats:italic> hindered <jats:styled-content style="fixed-case">DNA</jats:styled-content> demethylation at the two‐ to four‐cell stage in goat embryos and decreased <jats:italic>Nanog</jats:italic> expression in blastocysts. Overexpression of <jats:italic>Tet3</jats:italic> in somatic cells can initiate <jats:styled-content style="fixed-case">DNA</jats:styled-content> demethylation, reduce 5‐methylcytosine level, increase 5‐hydroxymethylcytosine level and promote the expression of key pluripotency genes. After <jats:styled-content style="fixed-case">SCNT</jats:styled-content>, overexpression of <jats:italic>Tet3</jats:italic> in donor cells corrected abnormal <jats:styled-content style="fixed-case">DNA</jats:styled-content> hypermethylation of cloned embryos and significantly enhanced <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic> developmental rate (<jats:italic>P </jats:italic><<jats:italic> </jats:italic>0.05). We conclude that overexpression of <jats:italic>Tet3</jats:italic> in donor cells significantly improves goat <jats:styled-content style="fixed-case">SCNT</jats:styled-content> efficiency.</jats:p>