Ascorbic acid improves parthenogenetic embryo development through TET proteins in mice

Biosci Rep. 2019 Jan 11;39(1):BSR20181730. doi: 10.1042/BSR20181730. Print 2019 Jan 31.

Abstract

The TET (Ten-Eleven Translocation) proteins catalyze the oxidation of 5mC (5-methylcytosine) to 5hmC (5-hydroxymethylcytosine) and play crucial roles in embryonic development. Ascorbic acid (Vc, Vitamin C) stimulates the expression of TET proteins, whereas DMOG (dimethyloxallyl glycine) inhibits TET expression. To investigate the role of TET1, TET2, and TET3 in PA (parthenogenetic) embryonic development, Vc and DMOG treatments were administered during early embryonic development. The results showed that Vc treatment increased the blastocyst rate (20.73 ± 0.46 compared with 26.57 ± 0.53%). By contrast, DMOG reduced the blastocyst rate (20.73 ± 0.46 compared with 11.18 ± 0.13%) in PA embryos. qRT-PCR (quantitative real-time PCR) and IF (immunofluorescence) staining results revealed that TET1, TET2, and TET3 expressions were significantly lower in PA embryos compared with normal fertilized (Con) embryos. Our results revealed that Vc stimulated the expression of TET proteins in PA embryos. However, treatment with DMOG significantly inhibited the expression of TET proteins. In addition, 5hmC was increased following treatment with Vc and suppressed by DMOG in PA embryos. Taken together, these results indicate that the expression of TET proteins plays crucial roles mediated by 5hmC in PA embryonic development.

Keywords: 5hmC; Ascorbic acid; DMOG; Parthenogenetic embryo; TET proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Methylcytosine / analogs & derivatives
  • 5-Methylcytosine / metabolism
  • Animals
  • Ascorbic Acid / pharmacology*
  • Blastocyst / drug effects*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Dioxygenases
  • Embryonic Development / drug effects
  • Female
  • Gene Expression Regulation, Developmental
  • Glycine / analogs & derivatives
  • Glycine / antagonists & inhibitors
  • Glycine / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Parthenogenesis / drug effects*
  • Parthenogenesis / genetics
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Signal Transduction

Substances

  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • TET1 protein, mouse
  • dimethyloxallyl glycine
  • 5-hydroxymethylcytosine
  • 5-Methylcytosine
  • Dioxygenases
  • Tet2 protein, mouse
  • Tet3 protein, mouse
  • Ascorbic Acid
  • Glycine