Zearalenone induces apoptosis and cytoprotective autophagy in primary Leydig cells

- ZEA-induced apoptosis by activation of the caspase cascade in primary Leydig cells.
- ZEA triggers autophagy in primary Leydig cells.
- Autophagy hinders apoptosis in ZEA-treated primary Leydig cells.

Zearalenone (ZEA) is a nonsteroidal estrogenic mycotoxin found in several food commodities worldwide. ZEA causes reproductive disorders, genotoxicity, and testicular toxicity in animals. However, little is known about the functions of apoptosis and autophagy after exposure to ZEA in Leydig cells. This study investigated the effects of ZEA on rat Leydig cells. Results showed that ZEA at different doses significantly inhibited the growth of Leydig cells by inducing apoptosis. ZEA treatment upregulated Bax expression, promoted cytochrome c release into the cytosol, and triggered mitochondria-mediated apoptosis. Consequently, caspase-9 and downstream effector caspase-3 were activated, followed by the cleavage of poly(ADP-ribose) polymerase (PARP), resulting in Leydig cell apoptosis. ZEA treatment also upregulated LC3-II and Beclin-1 expression, suggesting that ZEA induced a high level of autophagy. Pretreatment with chloroquine (an autophagy inhibitor) and rapamycin (an autophagy inducer) increased and decreased the rate of apoptosis, respectively, in contrast to other ZEA-treated groups. Autophagy delayed apoptosis in the ZEA-treated Leydig cells. Therefore, autophagy may prevent cells from undergoing apoptosis by reducing ZEA-induced cytotoxicity.