Apelin receptor antagonist (ML221) treatment has a stimulatory effect on the testicular proliferation, antioxidants system and steroidogenesis in adult mice

The expression of apelin and its receptor (APJ) has been shown in the hypothalamus-pituitary-testicular axis. It has also been suggested apelin and APJ are neuropeptide factors. The presence of apelin and APJ in the seminiferous tubules and interstitium might be predicted to act as a local regulator of testicular activity, although the function is not well known in the mice testis. In the present study, we have investigated the effects of APJ, antagonist, ML221 on the gonadotropin levels, testicular steroidogenesis, proliferation, apoptosis and antioxidant system. Our results showed that inhibition of APJ by ML221 increased the sperm concentration, circulating testosterone, FSH, LH levels and intra-testicular testosterone concentration. Furthermore, ML221 treatment stimulates the germ cell proliferation and antioxidant system in the testis. The expression of BCL2, AR was up-regulated whereas, the expression of BAX and active caspase3 was down-regulated after ML221 treatment. Immunohistocehmical analysis of AR also showed increase abundance in the spermatogonia, primary spermatocytes and Leydig cells of 150 μg/kg dose group. These findings suggest that in adult testis, the apelin system might have an inhibitory role in germ cell proliferation and a stimulatory role in apoptosis. It might also be suggested that the apelin system could be involved in the disposal mechanism for damaged germ cells during spermatogenesis via the down-regulation of AR.