Abstract
Sertoli cells play crucial roles in spermatogenesis and are impaired by aging. Icariin, a flavonoid from Epimedium, has been reported to exhibit anti-aging effects and improve testicular dysfunction in the clinical setting. However, whether icariin improves age-related degeneration of testicular function via protection from Sertoli cell injury remains unclear. In the present study, we evaluated the protective effect of icariin on Sertoli cell injury and explored the possible mechanism(s) in vivo and in vitro. Dietary administration of icariin for 4 months significantly ameliorated the age-related decline in testicular function by increasing testicular and epididymal weights and indices, sperm count and sperm viability, testicular testosterone and estradiol concentrations, and seminiferous tubule diameters and heights. In addition, icariin protected age-related Sertoli cells from injury as evidenced by an analysis of Sertoli cell number, ultrastructure, and function. Such changes were accompanied by upregulation of ERα and Nrf2 signaling in Sertoli cells. Parallel in vitro studies also demonstrated that icariin inhibited untoward effects on the TM4 mouse Sertoli cell line with concomitant upregulation of ERα and Nrf2 signaling. Conversely, ERα siRNA reversed icariin-mediated protection of Sertoli cell injury. Our data suggest that icariin effectively ameliorates age-related degeneration of testicular function by alleviating Sertoli cell injury via the ERα/Nrf2 signal-transduction pathway. Thus, mitigating Sertoli cell damage via the ERα/Nrf2 signaling pathway likely represents a promising strategy for the prevention of age-related testicular dysfunction.
Highlights
The Sertoli cell is the key somatic cell in the testis that facilitates testis formation and spermatogenesis by producing various proteins, including glial cell-derived neurotrophic factor (GDNF), promyelocytic leukemia zinc finger (PLZF), bone morphogenetic protein 4 (BMP4), and stem cell factor (SCF) (França et al, 2016; Vogl et al, 2018)
We assayed the levels of testicular testosterone and found that they were significantly decreased in the aging model group compared to the adult control group (Figure 1G)
We found that icariin effectively ameliorated age-related degeneration of testicular function through alleviation of Sertoli cell injury, which is the first time that this has been demonstrated
Summary
The Sertoli cell is the key somatic cell in the testis that facilitates testis formation and spermatogenesis by producing various proteins, including glial cell-derived neurotrophic factor (GDNF), promyelocytic leukemia zinc finger (PLZF), bone morphogenetic protein 4 (BMP4), and stem cell factor (SCF) (França et al, 2016; Vogl et al, 2018). Protecting Sertoli cells from injury during aging represents an effective strategy for age-related dysfunction of the testis
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