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

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.