Narayana Kilarkaje
Kuwait University, Kuwait
Title: Male germ cell DNA damage in diabetes: What is the counter strategy?
Biography
Biography: Narayana Kilarkaje
Abstract
Hyperglycemia up-regulates oxidative stress, which forms a basis for the onset of both macro- and micro-vascular diseases. In addition, hyperglycemia in males also induces hypogonadism, alterations in hypothalamo-hypophyseal-testicular hormonal axis, erectile dysfunction and infertility in both humans and animals. One of the serious effects of hyperglycemia in males is the induction of DNA damage in germ cells and spermatozoa. Hyperglycemia causes DNA single- and double-strand breaks. TUNEL and DNA fragmentation assays have reproducibly shown that hyperglycemia induces DNA double-strand breaks in immature germ cells, Sertoli cells and mature spermatozoa. Moreover, ELISA and immunohistochemistry/ immunofluorescence studies have shown significant increases in stage-dependent expression of 8-oxo-dG, a marker for base oxidation in the testes and also in spermatozoa. Although DNA repair mechanisms repair the damaged DNA, which seems to be associated with several molecular mechanistic pathways, including poly(ADP-ribose) polymerase, MAPKs and p53-p21 signaling, not all damaged DNA is recovered in germ cells. The cells with huge amount unrepaired DNA damage undergo apoptosis. Interestingly, supplementation of some antioxidants, for example, Resveratrol (trans-trihydroxystilbene) appears to be promising to alleviate the DNA damage in germ cells, at least in diabetic animals, but such attempts in humans have not been undertaken. Taken together, published scientific data from our laboratory and from that of other researchers indicate that diabetes-induced DNA damage in germ cells have widespread implications as regards to fertility and quality of offspring. Thus, there is a need to develop a counteracting strategy to alleviate the induced DNA damage.