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 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. Testes were removed 12 hours after treatments and subjected to total RNA preparation for examination of genes expression by real time PCR.

RESULTS:

1.Treatments of AGS-500 and AGS-534 after X-ray irradiation , significantly increased TERT variants expression 12 hours post treatments: Full TERT ( by 40%) , E2-289 (by 37% , 50% respectively ) and "Insertion" (by 99% , 111% respectively ).

An increase in relevant markers of spermatogenesis was observed; Acrosin level by 13% ; CREM and VASA levels by 50% and 40-60% (respectively); PCNA level increased by more than 25% and 55% (AGS-500 , AGS-534 respectively ).

CONCLUSIONS:

These results reflect the positive effects of AGS-treatments on the spermatogenic lineage cells and steroidogenesis process. The protective effects are manifested by elevation of genes which are responsible for germ cell genome integrity, proliferation and maturation.