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

Li Ling1, Feifei Hu2, Xiaoyan Ying2

  • 1a State Key Laboratory of Reproductive Medicine , Nanjing Medical University , Nanjing , China.

Cell Cycle (Georgetown, Tex.)
|June 10, 2017
PubMed

Insights

Histone deacetylase 6 (HDAC6) is crucial for mouse oocyte maturation. Inhibiting HDAC6 disrupts spindle formation, chromosome alignment, and kinetochore-microtubule attachments, impacting meiotic apparatus assembly.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Reproductive Biology

Background:

  • Histone deacetylases (HDACs) regulate critical cellular processes.
  • The specific role of HDAC6 in mammalian oocyte maturation is not well understood.
  • HDAC6 is known to influence transcriptional regulation, signal transduction, and development.

Purpose of the Study:

  • To investigate the function of HDAC6 in mouse oocyte maturation.
  • To determine the effects of HDAC6 inhibition on meiotic apparatus formation and function.
  • To explore the molecular mechanisms underlying HDAC6's role in oocyte development.

Main Methods:

  • Utilized Tubastatin A (TubA), a selective HDAC6 inhibitor.
  • Examined oocyte maturational progression and meiotic spindle morphology.
  • Employed confocal microscopy to assess kinetochore-microtubule attachments.
  • Measured α-tubulin acetylation levels.

Main Results:

  • HDAC6 inhibition led to maturation arrest in mouse oocytes.
  • Spindle morphology and chromosome alignment were significantly disrupted.
  • Kinetochore-microtubule attachments were compromised in TubA-treated oocytes.
  • HDAC6 inhibition increased α-tubulin acetylation, potentially affecting microtubule dynamics.

Conclusions:

  • HDAC6 plays a novel and essential role in mammalian oocyte maturation.
  • HDAC6 activity is critical for proper meiotic apparatus assembly and function.
  • Altered microtubule stability and dynamics due to changes in α-tubulin acetylation may underlie the observed defects.
Keywords:
chromosomecytoskeletonmeiosisoocytereproduction

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