Sperm chromatin integrity and fertility

Robaire, BDelbès, GHales, B. F

Although the standardized World Health Organization semen analysis protocol is a valuable predictor of fertility when the number, motility or morphology of spermatozoa is extremely low, this analysis has often proven to be an unreliable predictor for both fertility and infertility when this is not true. Over the past twenty years, it has become apparent that we need to understand the quality of the nuclear material being delivered by the spermatozoon to the oocyte. A wide range of techniques have been developed that include determination of the rate of sperm decondensation, of extent of breaks, cross-links and integrity of chromatin, its template function and its chromatin structure, as well as assessment of the epigenetic status. We have used several of these tests to determine the effects of age and cancer chemotherapeutic agents (cyclophosphamide, bleomycin, etoposide and cisplatin) on sperm chromatin structure, sperm production and progeny outcome in a rat model. We also have examined the effects of testicular cancer and chemotherapy on sperm chromatin integrity markers in adult men. In rat studies, we found that each of the assays used (acridine orange, TUNEL, chromomycin A3 and monobromine bimane) provided differing, complementary information about chromatin quality. Furthermore, DNA damage induced by chemotherapeutic alkylating agents was germ cell phase specific, with the most extensive effects occurring during histone hyperacetylation and transition protein deposition, a key point of sperm chromatin remodelling. By investigating the proteome of the sperm nucleus, we found significant alterations in sperm basic proteins as well as the selective induction of numerous nuclear matrix proteins involved in cell defense and detoxification. Spermatozoa with extensive nuclear damage fertilized ova effectively. In our clinical studies, we found that sperm DNA damage and abnormal DNA compaction was greater in men with testis cancer than controls...(AU)

Resumo apresentado no III International Symposium Animal Biology of Reproductive, São Pedro, SP, 22-24 out. 2010