Vitamin C treatment of embryos, but not donor cells, improves the cloned embryonic development in sheep

Abstract

Vitamin C is not only an antioxidant but also a regulator of epigenetic modifications that can enhance the activity of the ten‐eleven translocation (TET) family dioxygenases and promote the oxidation of 5‐methylcytosine (5mC) to 5‐hydroxymethylcytosine (5hmC). Here, we investigated the effects of vitamin C in regulating DNA methylation in sheep somatic cells or embryos in an effort to improve the cloned embryo development. Vitamin C treatment of sheep foetal fibroblast cells significantly increased the 5hmC levels but did not affect the 5mC levels in cells. After nuclear transfer, vitamin C‐treated donor cells could not support a higher blastocyst development rate than non‐treated cells. Although combination of serum starvation and vitamin C treatment could induce significant 5mC decrease in donor cells, it failed to promote the development of resultant cloned embryos. When cloned embryos were directly treated with vitamin C, the pre‐implantation development of embryos and the 5hmC levels in blastocysts were significantly improved. This beneficial role of vitamin C on embryo development was also observed in fertilized embryos. Our results suggest that vitamin C treatment of the embryos, but not the donor cells, can improve the development of cloned sheep embryos.

Long-Term Hypoxia Maintains a State of Dedifferentiation and Enhanced Stemness in Fetal Cardiovascular Progenitor Cells

“…The latter are aimed at cardiovascular therapies and cardiosurgical treatments of a variety of cardioangiopathies [3,4]. In addition, the establishment of permanent cardiovascular stem cell clones that exhibit augmented stemness properties as a result of expressing the genotypic and phenotypic traits related to their tissue-specific genomic, epigenomic and proteomic profiles could also be valuable for the generation of nuclear donor cells for modern assisted reproductive technologies (ARTs) such as cloning sheep and other mammalian species by somatic cell nuclear transfer (SCNT) [77][78][79]. Future work in these areas is needed to address these possibilities.…”

Lysophosphatidic Acid Accelerates Bovine In Vitro-Produced Blastocyst Formation through the Hippo/YAP Pathway

“…This study has demonstrated for the first time insightful and strongly evidence-based recognition of LPA-induced mechanisms underlying and identification of Hippo/YAP signaling pathway-related factors affecting not only onset and acceleration of blastocyst formation but also promotion of blastomere commitment and differentiation to ICM and TE cell lineages in bovine in vitro fertilization (IVF)-derived embryos. As a consequence, the LPA-triggered and Hippo/YAP pathway-mediated approaches could be widely applied to expedite the blastocyst formation by mammalian embryos that have been generated using other assisted reproductive technologies such as somatic cell nuclear transfer (SCNT) [ 35 , 36 , 37 ].…”

Reproduction of Sheep through Nuclear Transfer of Somatic Cells: A Bibliometric Approach

“…The first attempts to generate cloned embryos by blastomere separation and embryo bipartition were carried out in sheep, as was the generation of embryos by SCNT [8]. SCNT is a biotechnology with great potential in the reproduction of sheep with high genetic value [9], to conserve endangered wild sheep [10] and to generate transgenic sheep with biomedical purposes [11].…”