Interleukin 17D Enhances the Developmental Competence of Cloned Pig Embryos by Inhibiting Apoptosis and Promoting Embryonic Genome Activation

The cloning technique is important for animal husbandry and biomedicine because it can be used to clone superior breeding livestock and produce multipurpose genetically modified animals. However, the success rate of cloning currently is very low due to the low developmental efficiency of cloned embryos, which limits the application of cloning. The low developmental competence is related to the excessive cell death in cloned embryos. Interleukin 17D (IL17D) is required for the normal development of mouse embryos by inhibiting cell death. This study aimed to investigate whether IL17D can improve cloned pig embryo development by inhibiting cell death. Addition of IL17D protein to culture medium decreased the cell death level and improved the developmental ability of cloned pig embryos. IL17D treatment enhanced cloned pig embryo development by regulating cell death-associated gene pathways and promoting genome-wide gene expression, which is probably via up-regulating the expression of a gene called GADD45B. This study provided a new approach to improve the pig cloning efficiency by adding IL17D protein to the culture medium of cloned pig embryos. Cloned animals generated by the somatic cell nuclear transfer (SCNT) approach are valuable for the farm animal industry and biomedical science. Nevertheless, the extremely low developmental efficiency of cloned embryos hinders the application of SCNT. Low developmental competence is related to the higher apoptosis level in cloned embryos than in fertilization-derived counterparts. Interleukin 17D (IL17D) expression is up-regulated during early mouse embryo development and is required for normal development of mouse embryos by inhibiting apoptosis. This study aimed to investigate whether IL17D plays roles in regulating pig SCNT embryo development. Supplementation of IL17D to culture medium improved the developmental competence and decreased the cell apoptosis level in cloned porcine embryos. The transcriptome data indicated that IL17D activated apoptosis-associated pathways and promoted global gene expression at embryonic genome activation (EGA) stage in treated pig SCNT embryos. Treating pig SCNT embryos with IL17D up-regulated expression of GADD45B, which is functional in inhibiting apoptosis and promoting EGA. Overexpression of GADD45B enhanced the developmental efficiency of cloned pig embryos. These results suggested that IL17D treatment enhanced the developmental ability of cloned pig embryos by suppressing apoptosis and promoting EGA, which was related to the up-regulation of GADD45B expression. This study demonstrated the roles of IL17D in early development of porcine SCNT embryos and provided a new approach to improve the developmental efficiency of cloned porcine embryos.