Mechanisms by which in vitro meiotic arrest and sexual maturity improve developmental potential of mouse oocytes

Sci Rep. 2017 Nov 17;7(1):15763. doi: 10.1038/s41598-017-16119-5.

Abstract

To study the relationship between chromatin condensation, gene transcription and developmental competence during oocyte maturation and to explore the mechanisms by which meiotic arrest maintenance (MAM) and sexual maturity improve oocyte competence, we examined effects of MAM with roscovitine or db-cAMP on chromatin condensation, gene transcription and developmental potential of NSN or SN oocytes from prepubertal or adult mice. MAM with roscovitine improved the developmental competence and global gene transcription of prepubertal NSN (prep-NSN) and adult-SN oocytes while having no effect on those of prep-SN oocytes. MAM with db-cAMP facilitated neither development nor transcription in any type of oocytes. MAM with either roscovitine or db-cAMP promoted chromatin condensation of prep-NSN oocytes. MAM with roscovitine promoted gene transcription and chromatin condensation simultaneously through inhibiting cyclin-dependent kinase (CDK) 5 and 2, respectively. The results suggested that MAM with roscovitine improved oocyte competence by promoting gene transcription via inhibiting CDK5. Oocyte cytoplasmic maturation is correlated with gene transcription but not with chromatin condensation. The difference in developmental competence between prepubertal NSN and SN oocytes and between prepubertal and adult SN oocytes was because while the former had not, the latter had completed or acquired the ability for transcription of important genes.

MeSH terms

  • Alpha-Amanitin / pharmacology
  • Animals
  • Bucladesine / pharmacology
  • Cell Cycle Checkpoints* / drug effects
  • Cell Nucleolus / drug effects
  • Cell Nucleolus / metabolism
  • Chromatin / metabolism
  • Cumulus Cells / cytology
  • Cumulus Cells / drug effects
  • Cumulus Cells / metabolism
  • Cyclin-Dependent Kinase 5 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 5 / metabolism
  • Cytoplasm / drug effects
  • Cytoplasm / metabolism
  • Embryonic Development / drug effects
  • Female
  • Isoquinolines / pharmacology
  • Meiosis*
  • Mice
  • Oocytes / cytology*
  • Oocytes / drug effects
  • Oocytes / metabolism
  • RNA / genetics
  • RNA / metabolism
  • RNA Polymerase II / metabolism
  • Roscovitine / pharmacology
  • Sexual Maturation* / drug effects
  • Sulfonamides / pharmacology
  • Transcription, Genetic / drug effects

Substances

  • Alpha-Amanitin
  • Chromatin
  • Isoquinolines
  • Sulfonamides
  • Roscovitine
  • RNA
  • Bucladesine
  • Cyclin-Dependent Kinase 5
  • Cdk5 protein, mouse
  • RNA Polymerase II
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide