Di-n-butylphthalate (DBP) has been listed as an environmental priority pollutant in China due to its distinct biotoxicity. Epidemiological studies have shown that exposure to DBP is closely related to a series of congenital and acquired defects in the male reproductive system. The oxidative stress injury caused by DBP plays an important role in these defects. Previous studies have demonstrated that the Keap1/Nrf2 antioxidative pathway plays a protective role in DBP-induced oxidative stress injury. However, the further molecular regulation mechanism of the activation of Nrf2 pathway remains unclear. Here, we demonstrate that DBP caused testicular oxidative stress injury and Nrf2 pathway was activated in response to the injury in vivo and in vitro. Moreover, we validated that reduced level of USP15 attenuates DBP-induced oxidative stress injury through restraining the ubiquitylation and degradation of Nrf2. Notably, USP15 is confirmed as a target of miR-135b-5p and miR-135b-5p mediated inhibition of USP15 is involved in the DBP-induced oxidative stress injury. Collectively, these findings indicated that decreased level of USP15 functions a significant protective effect on the oxidative stress injury of testis caused by DBP via regulating the Keap1/Nrf2 signaling pathway.
Keywords: Di-N-butylphthalate; Nrf2; Oxidative stress injury; Testis; USP15.
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