2. Academic Validation
  3. Tubacin alleviate the reproductive toxicity of deoxynivalenol in mouse oocytes and zygotes via strengthening microtubule stability

Tubacin alleviate the reproductive toxicity of deoxynivalenol in mouse oocytes and zygotes via strengthening microtubule stability

  • Cell Commun Signal. 2025 Oct 3;23(1):417. doi: 10.1186/s12964-025-02432-4.
Hui Luo 1 2,  Jianhua Chen 1,  Zhihan Guo 1,  Yanyan Zhu 1,  Yipin Wang 1,  Tian Wu 1,  Siyue Yin 1,  Cao Li 1,  Youqiang Su 3,  Yao Chen 4,  Yun Qian 4,  Congxiu Miao 5,  Ruizhi Feng 6 7 8 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, 210029, China.
  • 2 Center for Reproductive Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
  • 3 Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, 266237, China.
  • 4 Clinical Center of Reproductive Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210008, China.
  • 5 Department of Reproductive Genetics, Heping Hospital of Changzhi Medical College, Key Laboratory of Reproduction Engineer of Shanxi Health Committee, Changzhi, 046000, China.
  • 6 State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, 210029, China. ruizhifeng@njmu.edu.cn.
  • 7 Clinical Center of Reproductive Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210008, China. ruizhifeng@njmu.edu.cn.
  • 8 Department of Reproductive Genetics, Heping Hospital of Changzhi Medical College, Key Laboratory of Reproduction Engineer of Shanxi Health Committee, Changzhi, 046000, China. ruizhifeng@njmu.edu.cn.
  • 9 Innovation Center of Suzhou Nanjing Medical University, Suzhou, 215005, China. ruizhifeng@njmu.edu.cn.
PMID: 41044645 DOI: 10.1186/s12964-025-02432-4
Abstract

Deoxynivalenol (DON) is one of the most common food contaminants, widely present in grain products. Studies using murine and porcine models show deoxynivalenol exposure impairs oocyte maturation and mitochondrial function; however, the exact mechanisms remain unclear. Here, we demonstrate that DON exposure markedly altered the microtubule nucleation-associated protein expression in oocytes. Pharmacological inhibition of HDAC6 with Tubacin rescued maturation arrest and restored expression of key microtubule regulators KIF11 and TPX2, which are key factors for microtubule nucleation and spindle stabilization. More importantly, we developed an in vivo TUBB8 oocyte-specific knock-in model. In our expressing human β-tubulin isotype model, Tubacin reconstructed normal spindles and drastically restored polar body extrusion in DON-exposed oocytes. Mechanistically, DON represses mRNA translation and disrupts ribosomal function. In our investigation, DON interfered with fertilized zygote cleavage by disrupting microtubule and microfilament networks, and Tubacin enhanced microtubule acetylation, stabilizing the network and rescuing developmental arrest. Taken together, this study establishes Tubacin's therapeutic potential against DON-induced reproductive toxicity, and validated the novel TUBB8 oocyte-specific knock-in mouse model as a rapid evaluation of exposure and potential treatment of environmental pollutants to female reproductive health.

Supplementary Information: The online version contains supplementary material available at 10.1186/s12964-025-02432-4.

Keywords

Deoxynivalenol; Multi-omics; Oocyte maturation; Spindle; Tubacin.

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