Supplementation of Maturation Medium with Folic Acid Affects DNA Methylation of Porcine Oocytes and Histone Acetylation of Early Developmental Stage Embryos

抄録

The present study examined the effect of supplementation of the maturation medium with folic acid on the developmental competence of porcine oocytes as well as on the global DNA methylation of oocytes and histone acetylation in early developmental stage embryos. Supplementation of the maturation medium with 100 μM folic acid improved the development ratio of the oocytes to the blastocyst stage compared with those of oocytes that were cultured with either 0 or 10 μM folic acid. The global DNA methylation levels of the oocytes that matured with 100 μM folic acid were higher than those of oocytes that were cultured without folic acid, while the global DNA methylation levels of the oocytes decreased during maturation. Addition of either folic acid or 1.2 mM N-acetyl-cysteine (NAC) to the maturation medium significantly reduced the levels of reactive oxygen species in the oocytes. Supplementation of maturation medium with folic acid significantly enhanced the acetylation level of H4K8 and decreased the expression of histone deacetylase 1 (HADC1), whereas the addition of NAC did not affect the acetylation levels of H4K8 or HADC1. In addition, supplementation of maturation medium with 1.2 mM NAC did not improve the development rate to the blastocyst stage. In conclusion, folic acid added to the maturation medium affects not only the DNA methylation state of oocytes, but also the histone acetylation of early developmental stage embryos, as well as improving the developmental competence of the oocytes.