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Vitamin D3 regulates apoptosis and proliferation in the testis of D-galactose-induced aged rat model.

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.

SUBMITTER: Jeremy M

PROVIDER: S-EPMC6773724 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Vitamin D3 regulates apoptosis and proliferation in the testis of D-galactose-induced aged rat model.

Jeremy Malsawmhriatzuala M Gurusubramanian Guruswami G Roy Vikas Kumar VK

Scientific reports 20191001 1

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 o ...[more]

PMID: 31575929

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Project description:Vitamin D3 and its analogues have recently been shown to enhance the anti-tumour effects of 5- Fluorouracil (5-FU) both in vitro and in xenograft mouse model of colon cancer. This study measured the potential mechanism(s) by which vitamin D3 could synergise the tumouricidal activities of 5-FU in azoxymethane (AOM) rat model of colon cancer.Seventy-five male Wistar rats were divided equally into 5 groups: Control, AOM, AOM-treated by 5-FU (5-FU), AOM-treated by vitamin D3 (VitD3), and AOM-treated by 5-FU?+?vitamin D3 (5-FU/D). The study duration was 15 weeks. AOM was injected subcutaneously for 2 weeks (15 mg/kg/week). 5-FU was injected intraperitoneally in the 9th and 10th weeks post AOM (8 total injections were given: 12 mg/kg/day for 4 successive days, then 6 mg/kg every other day for another 4 doses) and oral vitamin D3 (500 IU/rat/day; 3 days/week) was given from week 7 post AOM till the last week of the study. The colons were collected following euthanasia for gross and histopathological examination. The expression of ?-catenin, transforming growth factor-?1 (TGF-?1), TGF-? type 2 receptor (TGF-?R2), smad4, inducible nitric oxide synthase (iNOS), and heat shock protein-90 (HSP-90) proteins was measured by immunohistochemistry. In colonic tissue homogenates, quantitative RT-PCR was used to measure the mRNA expression of Wnt, ?-catenin, Dickkopf-1 (DKK-1) and cyclooxygenase-2 (COX-2) genes, while ELISA was used to measure the concentrations of TGF-?1, HSP-90 and COX-2 proteins.Monotherapy with 5-FU or vitamin D3 significantly decreased the number of grown tumours induced by AOM (P?<?0.05); however, their combination resulted in more significant tumouricidal effects (P?<?0.05) compared with monotherapy groups. Mechanistically, vitamin D3/5-FU co-therapy significantly decreased the expression of Wnt, ?-catenin, iNOS, COX-2 and HSP-90 and significantly increased the expression of DKK-1, TGF-?1, TGF-?R2, smad4 (P?<?0.05), in comparison with their corresponding monotherapy groups.Vitamin D3 and 5-FU synergise together and exhibit better anticancer effects by modulating Wnt/?-catenin pathway, TGF-?1 signals, iNOS, COX-2 and HSP-90. Further studies are required to illustrate the clinical value of vitamin D supplementation during the treatment of colon cancer with 5-FU in human patients.

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Dataset Information

Vitamin D3 regulates apoptosis and proliferation in the testis of D-galactose-induced aged rat model.

Publications

Vitamin D3 regulates apoptosis and proliferation in the testis of D-galactose-induced aged rat model.

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