Postnatal developmental expression of apelin receptor proteins and its role in juvenile mice testis

The expression of apelin system has been shown in the adult testis of rat and mice. It has also been emphasized that regulation of testicular activity in early stages is important to sustain normal testicular activity in adulthood. Since the expression of apelin receptor (APJ) has been shown in the adult testis, moreover, developmental expression of APJ and its role has not been explored yet. Thus, we have examined the testicular expression of APJ during postnatal stages with special reference to proliferation, apoptosis and hormone secretion in early post-natal stage. Postnatal analysis showed that circulating apelin was lowest at PND1 and maximum at PND42. Among testosterone, estrogen and androstenedione, only circulating testosterone showed a gradual increase from PND1 to PND42. Testicular expression of APJ was also developmenatly regulated from PND1 to PND42, revealing a positive correlation with circulating apelin, testosterone, and androstenedione. Immunohistochem-ical study showed that APJ was mainly confined to Leydig cells of early postnatal stages, whereas, seminiferous tubules at PND42 showed immunostaining in the round spermatids. APJ inhibition from PND14-PND20 by ML221 suppressed the testicular proliferation, increased apoptosis and increased estrogen secretion. However, expression of AR was down-regulated by ML221 treatment. Furthermore, ML221 decreased the abundance of p-Akt. In vitro study also showed that APJ antagonist, ML221 decreased AR expression. These results suggests that apelin signaling during early developmental stages might be required to stimulate the germ cell proliferation, and inhibition of apoptosis. Both in vivo and in vitro study have shown that expression of AR was regulated by apelin signaling. Since the first wave spermatogenesis involves proliferation and apoptosis, therefore, further study would be required to unravel the exact mechanism of apelin mediated regulation of testicular activity during early postnatal stages. In conclusion, the present results are an indicative of apelin mediated signaling during early postnatal stage for regulation of germ cell proliferation, apoptosis and AR expression.

Automated summary

The expression of the apelin system in the adult testis of rat and mice has been shown. It has been emphasized that regulation of testicular activity in early stages is important for sustaining normal testicular activity in adulthood. The expression of apelin receptor (APJ) in the adult testis has been shown, but the developmental expression of APJ and its role have not been explored. The present study examined the testicular expression of APJ during postnatal stages and found that it is developmentally regulated with a positive correlation with circulating apelin, testosterone, and androstenedione. Inhibition of APJ resulted in suppressed testicular proliferation, increased apoptosis, and increased estrogen secretion. AR expression was also down-regulated by APJ inhibition. These findings suggest that apelin signaling during early developmental stages is required for stimulating germ cell proliferation and inhibiting apoptosis. The exact mechanism of apelin-mediated regulation of testicular activity during early postnatal stages needs further investigation. The results indicate the importance of apelin-mediated signaling in regulating germ cell proliferation, apoptosis, and AR expression during early postnatal stage.