Involvement of ARTS in bisphenol A-induced apoptosis of mouse Leydig cells

As a widely used organic chemical raw material in the world, bisphenol A (BPA) can induce apoptosis in mouse Leydig cells, yet the underlying mechanism remains insufficiently elucidated. Herein, we confirmed that BPA could induce apoptosis of TM3 cells, accompanied with the upregulation of apoptosis-related protein in the TGF-β signaling pathway (ARTS). Overexpression of ARTS promoted apoptosis of TM3 cells, while ARTS depletion attenuated BPA-induced apoptosis of the cells, indicating that ARTS plays a key role in BPA-induced apoptosis of mouse Leydig cells. Subsequently, BPA was found to increase the expression of transcription factor p53 in the cells. Interestingly, overexpression of p53 enhanced the expression of ARTS and induced apoptosis of TM3 cells, while knockdown of p53 by siRNA attenuated the upregulation of ARTS and the induction of apoptosis caused by BPA, implying that BPA induces apoptosis of mouse Leydig cells through p53/ARTS signals. In addition, we also found that oxidative stress was involved in BPA-induced apoptosis of TM3 cells through p53/ARTS signals. Taken together, these findings suggest that BPA-triggered oxidative stress activates p53/ARTS signaling pathway, thereby inducing apoptosis of mouse Leydig cells.