The effect of cell penetrating peptide-conjugated coactivator-associated arginine methyltransferase 1 (CPP-CARM1) on the cloned mouse embryonic development

• Published in: Scientific reports Vol. 8; no. 1; pp. 16721 - 9
• Main Authors: Bang, Jae-Il, Lee, Eun-Hye, Lee, Ah Reum, Il Lee, Jin, Choi, Seo Hye, Seol, Dong-Won, Park, Chang-Hwan, Lee, Dong Ryul
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.11.2018; Nature Publishing Group
• Subjects: 13; 13/1; 13/106; 14; 38; 631/136/1455; 631/136/2435; 64; 64/60; 82; Arginine; Blastocysts; CDX2 protein; Cell culture; Cell number; Cloning; DNA methylation; Embryogenesis; Gene expression; Humanities and Social Sciences; Mammalian cells; multidisciplinary; Nuclear transfer; Oct-4 protein; Peptides; Pluripotency; Protein arginine methyltransferase; Proteins; Science; Science (multidisciplinary); Somatic cell nuclear transfer; Somatic cells; Supplements; Trophectoderm; Implantation Rate; Somatic Cell Nuclear Transfer (SCNT); Inner Cell Mass (ICM); Cell-penetrating Peptides (CPP); Coactivator-associated Arginine Methyltransferase 1 (CARM1)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-35077-0

Abnormalities in gene expression that negatively affect embryonic development are frequently observed in cloned embryos generated by somatic cell nuclear transfer (SCNT). In the present study, we successfully produced a cell-penetrating peptide (CPP)-conjugated with coactivator-associated arginine methyltransferase 1 (CARM1) protein from mammalian cells and confirmed introduction into donor somatic cells and cloned 8-cell embryos within 3 hours after addition to culture medium. In addition, H3R17 dimethylation and embryonic development up to the blastocyst stage were increased in the group treated with exogenous CPP-CARM1 protein compared with the untreated group (control). Interestingly, the number of total cells and trophectoderm in blastocysts as well as implantation rate were significantly increased in the CPP-CARM1 protein-treated group. However, the cell number of inner cell mass (ICM) was not changed compared with the control group; similarly, expression of pluripotency-related genes Oct4 and Nanog (ICM markers) was not significantly different between groups. On the other hand, expression of the implantation-related gene Cdx2 (trophectoderm marker) was transiently increased after treatment with CPP-CARM1 protein. On the basis of these results, we conclude that supplementation with exogenous CPP-CARM1 protein improves embryonic development of cloned embryos through regulation of histone methylation and gene expression. In addition, our results suggest that CPP-CARM1 protein may be a useful tool for strengthening implantation of mammalian embryos.