Endosulfan as a new member of persistent organic pollutants has been shown to induce apoptosis in various animal models. However, the mechanism underlying endosulfan-induced apoptosis has not been well elucidated thus far. <i>Caenorhabditis elegans</i> N2 wild type and mutant strains were used in the present study to clarify the roles of the mitochondria, the insulin/insulin-like growth factor-1 (IGF-1) signaling pathway, and mitogen-activated protein kinase (MAPK) cascades in -endosulfan-induced apoptosis. Our results demonstrated a dose- and time-dependent increase of apoptosis in the meiotic zone of the gonad of <i>C. elegans</i> exposed to graded concentrations of endosulfan. The expression levels of <i>
sod-3</i>, localized in the mitochondrial matrix, increased greatly after endosulfan exposure. A significant increase in germ cell apoptosis was observed in abnormal methyl viologen sensitivity-1 (<i>
mev-1</i>(<i>kn-1</i>)) mutants (with abnormal mitochondrial respiratory chain complex II and higher ROS levels) compared to that in N2 at equal endosulfan concentrations. We found that the insulin/IGF-1 signaling pathway and its downstream Ras/ERK/MAPK did not participate in the endosulfan-induced apoptosis. However, the apoptosis in the loss-of-function strains of JNK and
p38 MAPK signaling pathways was completely or mildly suppressed under endosulfan stress. The apoptotic effects of endosulfan were blocked in the mutants of <i>
jnk-1</i>/JNK-MAPK, <i>
sek-1</i>/MAP2K, and <i>
pmk-1</i>/p38-MAPK, suggesting that these downstream genes play an essential role in endosulfan-induced germ cell apoptosis. In contrast, the <i>
mkk-4</i>/MAP2K and <i>
nsy-1</i>/MAP3K were only partially involved in the apoptosis induction. Our data provide evidence that endosulfan increases germ cell apoptosis, which is regulated by mitochondrial function, JNK and
p38 MAPK cascades. These findings contribute to the understanding of the signal transduction pathways involved in endosulfan-induced apoptosis.