Melatonin significantly improves the developmental competence of bovine somatic cell nuclear transfer embryos

J Pineal Res. 2015 Nov;59(4):455-68. doi: 10.1111/jpi.12275. Epub 2015 Sep 22.


Somatic cell nuclear transfer (SCNT) is a promising technology, but its application is hampered by its low efficiency. Hence, the majority of SCNT embryos fail to develop to term. In this study, the antioxidant melatonin reduced apoptosis and reactive oxygen species (ROS) in bovine SCNT embryos. It also increased cell number, inner cell mass (ICM) cell numbers, and the ratio of ICM to total cells while improving the development of bovine SCNT embryos in vitro and in vivo. Gene expression analysis showed that melatonin suppressed the expression of the pro-apoptotic genes p53 and Bax and stimulated the expression of the antioxidant genes SOD1 and Gpx4, the anti-apoptotic gene BCL2L1, and the pluripotency-related gene SOX2 in SCNT blastocysts. We also analyzed the epigenetic modifications in bovine in vitro fertilization, melatonin-treated, and untreated SCNT embryos. The global H3K9ac levels of melatonin-treated SCNT embryos at the four-cell stage were higher than those of the untreated SCNT embryos. We conclude that exogenous melatonin affects the expression of genes related to apoptosis, antioxidant function, and development. Moreover, melatonin reduced apoptosis and ROS in bovine SCNT embryos and enhanced blastocyst quality, thereby ultimately improving bovine cloning efficiency.

Keywords: cattle; embryo development; melatonin; reactive oxygen species; somatic cell nuclear transfer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Cattle
  • Cell Line
  • Embryonic Development / genetics
  • Embryonic Development / physiology
  • Female
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Melatonin / pharmacology*
  • Nuclear Transfer Techniques*
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1


  • Reactive Oxygen Species
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Melatonin

Associated data

  • GENBANK/AF104906
  • GENBANK/AF245489
  • GENBANK/AW461431
  • GENBANK/AY606044
  • GENBANK/AY849926
  • GENBANK/DQ069776
  • RefSeq/NM_001076414
  • RefSeq/NM_001077840
  • RefSeq/NM_001105463
  • RefSeq/NM_1738941
  • RefSeq/NM_174087
  • RefSeq/NM_174352
  • RefSeq/NM_174580
  • RefSeq/NM_1746152
  • RefSeq/NM_1747703
  • RefSeq/XM_871005