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Abstract
Tubastatin A (Tub-A), a highly selective histone deacetylase 6 (HDAC6) inhibitor, has been widely used as a cytotoxic anticancer agent, or for the treatment of patients with asthma. However, the potential toxicity of Tub-A on oocyte maturation and asymmetric division is still unclear. Therefore, the present study was designed to examine the effect and potential regulatory role of Tub-A on the meiotic maturation of oocytes. We observed that Tub-A treatment induced an increased level of the acetylation of α-tubulin, and a failure of spindle migration and actin cap formation. Based on the spindle structure, most Tub-A treated oocytes were arrested in an MI-like or a GVBD-like stage and exhibited decondensed chromosomes in a dose dependent manner. Moreover, Tub-A treatment decreased the protein expression of mTOR, a factor responsible for spindle formation, and the expression of mDia1, an inhibitor of actin assembly, in an HDAC6 expression-dependent manner. Importantly, following Tub-A supplementation, most oocytes failed to extrude the first polar body, which indicates that these defects are closely linked to abnormal oocyte maturation. Taken together, our data demonstrates that HDAC6 is one of the essential factors for oocyte maturation and asymmetric division via the HDAC6/mTOR or mDia1 pathway in mice.
Highlights
In mammals, oocyte maturation requires a precise and orderly multistage process[1, 2]
This study demonstrated that the selective histone deacetylase 6 (HDAC6) inhibitor, Tubastatin A (Tub-A), disrupted the spindle migration, actin cap formation, and asymmetric division during oocyte maturation
We first demonstrated that HDAC6 expression is an essential factor for mouse oocyte maturation and provided direct evidence that HDAC6 is critically involved in the asymmetric division of the oocyte
Summary
Oocyte maturation requires a precise and orderly multistage process[1, 2]. Even though Tub-A has no significant side effects on normal cells, a previous study demonstrated that the selective inhibition of HDAC6 can promote hyperacetylation of α-tubulin and decrease cell motility[10, 11]. This area of study is important because histone deacetylase inhibitors can be used as a treatment for airway remodelling in patients with asthma[10]. This study was aimed to investigate the influence of HDAC6 on oocyte meiotic maturation and asymmetric division following treatment with Tub-A
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