Asprosin modulates testicular functions during ageing in mice

Abstract

Ageing is a gradual and multi-factorial process with a significant impact on fertility. The mechanism of declined testicular functions with age remains elusive. Asprosin is a novel fasting-induced gluconeogenic adipokine that regulates glucose homeostasis. However, the expression and potential role of asprosin in testicular functions with age are largely unexplored. So, the current study was aimed to examine the variation in asprosin expression in the mice testis and its correlation with OLFR734 receptor, insulin receptor (IR), GLUT-8 and various steroidogenic markers at different stages of postnatal development. The result demonstrated the highest expression of asprosin in reproductively active mice, which decreased significantly in aged mice testis. Asprosin expression declined simultaneously with declining testosterone production, testicular glucose and expression of OLFR734, IR, GLUT-8 and AR in aged mice testis. This suggests that declining asprosin expression with advancing age may be a causative factor for regressive changes in the testis. Further, the present study also evaluated the in vitro effect of asprosin on testicular functions of aged mice testis. The results showed that asprosin treatment improves testicular functions by stimulating the expression of OLFR734, StAR, 3β-HSD,17β-HSD, IR, GLUT-8, MCT-2&4, PCNA, Bcl2 proteins alongwith increased testosterone, insulin and lactate biosynthesis. Collectively, these findings indicate that a marked decline in asprosin and its receptor OLFR734 expression may result in decreased insulin sensitivity and glucose transport, leading to regressive changes in aged mice testis. Treatment of asprosin can possibly restore the testicular functions of aged mice by augmenting the testosterone, insulin and glucose levels.