Increasing Telomerase by Ags Compounds Protect Mouse Testes from Damages Induced By X-Ray Radiation

INRODUCTION:
Telomerase Enzyme is responsible for the re-elongation of telomeres and for genome stability and involves in anti-apoptotic, DNA repair and processes. During spermatogenesis, telomerase is active and its subunit TERT is expressed. We postulate that by increasing telomerase in the testis we may protect them from the damaging effects of radiation.

AIM:
To examine the effect of a transient increase of telomerase, by telomerase activators on irradiated- induced male infertility using a mouse model.

MATERIALS:
ICR mice (3 and 16 months old) were injected with 6mg/kg of AGS-500 or AGS-534, or mice were subjected to X-ray radiation (2.5 Gy) followed by immediately injection of AGS compounds. Control mice were untreated or vehicle treated with or without exposure to X-ray radiation. The testes were removed at different times after treatments and subjected to cell proteins extraction or total RNA preparation for the examination of telomerase activity by TRAP assay, and telomerase expression by real time PCR. Testes were also taken for immunohistochemical and immunohistofluorescence analysis with various spermatogenesis markers. Characterization of sperm was made: amount, motility and morphology.

RESULTS:
We previously showed that treatment of X-ray irradiated mice with AGS compounds protected the testis tissue from the damaging effects of Xray and increased sperm count compared to irradiated testes. Here we show that:
1. X-ray and X-ray+ DMSO treatments led to a significant decrease in testis cell proliferation capacity, 9 and 30 days post radiation.In addition, significant tissue damage in the cell layers of the seminiferouse tubules was detected. A significant increase in cell proliferation was observed in AGS-500 treated mice.
2. Treatments of AGS-500 and AGS-534 increased TERT expression 12 hrs after irradiation mainly in spermatozoa and spermatogonia layers.
3. Treatment of AGS-534 improves sperm count and motility in old mice.

CONCLUSIONS:
Increasing telomerase by AGS compounds in X-ray irradiated testes significantly protected the tissue from the damaging effects of radiation and elevates sperm count and motility in the epididymis, suggesting the potential of telomerase increasing compounds in restoration of the spermatogenesis process in irradiated and damaged testes or in old mice.