Abstract
The age-associated imbalances between proliferation and apoptosis lead to impaired spermatogenesis and infertility. The age-associated decline in vitamin D3 levels has been reported and suggested the anti-aging potential of vitamin D3. However, the age-associated decline levels of vitamin D3 has not been studied in relation to the testicular activity. Thus, we investigated the effect of vitamin D3 on the expression of testicular proliferation markers, apoptotic markers, antioxidants system and oxidative stress in a D-gal-induced aged rat model. The present study investigated the levels of vitamin D3 and AGE in serum and testes along with the expression of the AGE-receptor (AGER) in the testis. Vitamin D3 treatment significantly increases cell proliferation and decreases apoptosis in a D-gal-induced aged rat testis. Furthermore, vitamin D3 significantly decreases oxidative stress in aged rat testis by improving the antioxidant defense systems. The expression of AGER was down-regulated by vitamin D3 treatment in aged testis. The circulating and intra-testicular AGE was higher in aged groups, however, only circulating vitamin D3 levels decreased in aged groups. The immunolocalization of VDR showed increased immunostaining in the testis by vitamin D3 treatment. Thus, it can be concluded that vitamin D3 delays testicular senescence by regulating proliferation and apoptosis.
Highlights
Vitamin D3 is traditionally known for its action for maintaining and regulating calcium and phosphorus homeostasis
To clarify whether vitamin D3 would be involved in the regulation of testicular proliferation during aging, we have investigated the effect of vitamin D3 on GCNA and PCNA, which are well-known markers for cell proliferation
Western blot analysis showed a significant (P < 0.05) down-regulation of GCNA and PCNA in D-gal-induced aged rat testis (DG) compared to all other groups (Fig. 1A,B). Both dose of vitamin D3 (DG40D and DG400D) significantly (P < 0.05) up-regulated the expressions of GCNA and PCNA compared to the aged group (DG)
Summary
Vitamin D3 is traditionally known for its action for maintaining and regulating calcium and phosphorus homeostasis. The decline of circulating vitamin D3 has been reported in several aging-related pathophysiological conditions[16] This decline of vitamin D has become a major health concern[17] and suggested that the number of people suffering from vitamin D deficiency would increase and elderly people www.nature.com/scientificreports/. Since vitamin D3 is a well-known antioxidant, its role in testicular aging has not been explored in relation to germ cell proliferation and apoptosis. A recent study revealed that vitamin D deficiency impairs testicular development and spermatogenesis by inhibiting testicular germ cell proliferation[24]. It is logical to hypothesize that vitamin D3 might ameliorate age-associated testicular dysfunction in D-galactose treated animal model by regulating proliferation, apoptosis and antioxidant system. To the best of our knowledge, the present study will be the first to demonstrate the role of vitamin D3 in testicular proliferation and apoptosis in aged rodent animal model
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