Direct actions of adiponectin on changes in reproductive, metabolic, and anti-oxidative enzymes status in the testis of adult mice

Abstract

Obesity is a major health problem that is linked to decreased sperm count. It is hypothesized that an obesity-associated reduction in adiponectin secretion may be responsible for impairment of spermatogenesis. Therefore, the aim of the study was to evaluate the direct role of adiponectin in spermatogenesis and steroid synthesis in adult mice. This study showed that adiponectin receptors (AdipoR1 and AdipoR2) were localized in Leydig cells and seminiferous tubules in the testis of adult mice. The result of the in vitro study showed the direct action of adiponectin on spermatogenesis by stimulating cell proliferation (PCNA) and survival (Bcl2) and by suppressing cell apoptosis. Treatment of testis with adiponectin also enhanced transport of the energetic substrates glucose and lactate to protect cells from undergoing apoptosis. Adiponectin treatment further showed a significant reduction in oxidative stress and nitric oxide. Our findings suggest that adiponectin effectively facilitates cell survival and proliferation, as well as protects from apoptosis. Thus, adiponectin treatment may be responsible for enhancing sperm counts. Interestingly, this study showed the stimulatory effect of adiponectin in spermatogenesis but showed an inhibitory effect on testosterone and estradiol synthesis in the testes. Based on the present study, it is hypothesized that systemic adiponectin treatment may be a promising therapeutic strategy for the improvement of spermatogenesis and sperm count.

Mechanisms of Adiponectin Action in Fertility: An Overview from Gametogenesis to Gestation in Humans and Animal Models in Normal and Pathological Conditions

“…Adiponectin regulates both spermatogenesis and steroidogenesis in adult testis via its two receptors, AdipoR1 and AdipoR2 [89,99]. Indeed, in vitro experiments showed that adiponectin acted directly in Leydig cells to decrease androgen secretion, which was associated with inhibition of the StAR protein in Leydig cells [94].…”

“…However, adiponectin did not modulate anti-Mullerian hormone (AMH) transcript levels [101]. Another important role of adiponectin is to maintain insulin sensitivity by stimulating glucose uptake in the testes [99]. Indeed, intratesticular glucose level was shown to be associated with testicular functions like testosterone production [102].…”

Comparative Effects of Estrogen and Phytoestrogen, Genistein on Testicular Activities of Streptozotocin-Induced Type 2 Diabetic Mice

“…61 Lactate produced in the Sertoli cells is transported to the germ cells and prevent apoptosis. 62 These findings thus suggest that treatment with genistein increases production of antioxidant enzymes and lactate which contributes to suppress germ cell apoptosis and improves spermatogenesis in T2D mice.…”

Growth Hormone and Insulin-like Growth Factor-I: Novel Insights into the Male Reproductive Health

“…Interestingly, GH-induced insulin/IGF family of growth factors activates glucose transporter 8 (GLUT8) which helps in chronological conversion of glucose into lactate by mature Sertoli cells [79,80]. Notably, lactate is a preferred energy metabolite serving the energy requirement for proper testicular functioning and development of spermatogenic cells [81][82][83]. Also, the Figure 1.…”