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Acetylation of FOXO3 by p300/CBP and deaetylation by sirtuins (Sirt1, Sirt2 and Sirt3) also provide a fine-tuning regulatory mechanism of FOXO3 activity depending on the cellular context and types of stress stimuli 81 - 83

Against the backdrop of altered membrane permeability and metabolic amplification effects, ROS (particularly the highly reactive hydroxyl radical, OH) are more likely to accumulate in the perinuclear microenvironment and penetrate the nuclear envelope, directly attacking sperm DNA

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In nonresponsive cases, doctors can consider using parenteral B12, especially if oral B12 treatment has been used in the past or when serum vitamin B12 is not normalized (Table 2)