The mRNA of the mitochondrial uncoupling protein 2 (UCP2) was up-regulated by cryptorchidism, a testicular hyperthermic condition under which germ cells undergo severe apoptosis. We investigated whether UCP2 was able to protect germ cells from hyperthermia-induced apoptosis. UCP2 was predominantly present in elongate spermatids under normal conditions, and was detected in all germ cells with its level significantly increased if the testes were exposed to 43 degrees C for 5 min. Such a short heat exposure was non-lethal and enabled the preconditioned cells to be resistant to apoptosis induced by a longer hyperthermic treatment (15 min). While hyperthermia resulted in oxidative stress in mouse testes, it did not change the total anti-oxidative capacity. Indeed, overexpression of UCP2 in the GC-2 germ cell line protected the cells from radical oxygen species (ROS)-induced apoptosis. Taken together, we propose that UCP2 may represent an effective weaponry used by germ cells to combat ROS-induced apoptosis. (C) 2007 Elsevier Inc. All rights reserved.