HDAC6 inhibition disrupts maturational progression and meiotic apparatus assembly in mouse oocytes

Cell Cycle. 2018;17(5):550-556. doi: 10.1080/15384101.2017.1329067. Epub 2018 Apr 3.

Abstract

Histone deacetylases (HDACs) have been implicated in diverse biologic processes including transcriptional regulation, signal transduction, and developmental control. However, the role of HDAC6 in mammalian oocytes remains unknown. In the present study, by using Tubastatin A (TubA), a selective HDAC6 inhibitor, we examined the effects of HDAC6 on maturational progression and meiotic apparatus in mouse oocytes. We found that HDAC6 inhibition results in maturation arrest and disruption of spindle morphology and chromosome alignment. In line with this observation, confocal microscopy revealed that kinetochore-microtubule attachment, a critical mechanism controlling chromosome movement, is compromised in TubA-treated oocytes markedly. Moreover, we noted that HDAC6 inhibition significantly increases the acetylation levels of α-tubulin in mouse oocytes, which may be associated with the defective phenotypes of TubA-treated oocytes by altering microtubule stability and dynamics. In sum, we discover a novel function of HDAC6 during oocyte maturation and suggest a potential pathway modulating meiotic apparatus assembly.

Keywords: chromosome; cytoskeleton; meiosis; oocyte; reproduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Animals
  • Cells, Cultured
  • Chromosome Segregation / drug effects
  • Histone Deacetylase 6 / antagonists & inhibitors
  • Histone Deacetylase 6 / metabolism*
  • Hydroxamic Acids / pharmacology
  • Indoles / pharmacology
  • Kinetochores / metabolism
  • Meiosis* / drug effects
  • Mice
  • Mice, Inbred ICR
  • Microscopy, Confocal
  • Microtubules / metabolism
  • Oocytes / metabolism
  • Spindle Apparatus / drug effects
  • Spindle Apparatus / metabolism*
  • Tubulin / metabolism

Substances

  • Hydroxamic Acids
  • Indoles
  • Tubulin
  • tubastatin A
  • Histone Deacetylase 6

Grants and funding

This work was supported by National Natural Science Foundation (31571543 to QW and 31601202 to JG) of China.