Sperm concentration, hyaluronic acid-binding capacity, aneuploidy and persistent histones in testicular cancer.

Abstract

Are the quantitative and qualitative characteristics of semen samples of patients with testicular cancer (TC), prior to anticancer therapy, different from infertile oligozoospermic (IO) and normozoospermic (NZ) age-matched men? Sperm concentration in TC patients was significantly decreased with no difference in estimated numerical chromosome aberrations and nuclear decondensation compared with NZ men, while the infertile, oligozoospermic men had significantly poorer sperm qualitative characteristics versus the TC group overall and oligozoospermic patients with TC. Spermatogenesis is altered in TC patients at the time of diagnosis. However, the mechanism responsible for the decreased semen quantity in patients with TC is not well understood. Anticancer treatment may have gonadotoxic side effects and post-treatment fertility cannot be predicted. Before commencing anticancer treatment, cryopreservation may be suggested to preserve fertility but there are no data regarding the risk of genetic aberrations in these sperms. This is a cross-sectional study examining semen from 28 patients with TC, 20 IO and 20 NZ age-matched men attending the Andrology Center and the Sperm Cryopreservation Laboratory of the Medical and Health Science Center, University of Debrecen. Semen samples from patients with TC were collected after orchidectomy, but prior to anticancer treatment. Semen samples from TC patients recruited over a period of 4 years were studied. Based on their sperm concentration, TC patients were subgrouped into an oligozoospermic TC (TCO) and a normozoospermic TC group. For statistical analysis, the normal group (NZ + IO) comprised non-tumorous NZ and IO men. The ejaculates were assessed as per World Health Organization guidelines. Hyaluronic acid (HA)-binding capacity was the functional test. To determine the numerical chromosome aberrations, we used multi-color fluorescence in situ hybridization. Aniline blue (AB) staining was performed as a nuclear decondensation marker test. The results did not reveal any significant difference in disomy of sex chromosomes and chromosome 17, diploidy and estimated numerical chromosome aberrations and AB staining results upon comparing the NZ and TC groups, although the sperm concentration (P < 0.001) and HA-binding capacity (P < 0.001) were lower in the TC group. Estimated numerical chromosome aberrations (P < 0.001), AB staining (P < 0.001) and HA-binding capacity (P = 0.019) were lower in the infertile, oligozoospermic group when compared with the patients with TC. The TCO group had significantly better results in every examined parameter than the infertile, oligozoospermic group. In the non-tumorous control group (NZ + IO), a significant (P < 0.001) correlation (Spearman's rho = r) was found between sperm concentration and aneuploidy rate (r = -0.642), AB staining (r = -0.876) and HA binding (r = 0.842); the HA-binding capacity was related to the aneuploidy rate (r = -0.678) and the AB staining (r = -0.811); and there was significant correlation between aneuploidy and AB staining (r = 0.559). In the TC group, apart from the negative correlation between sperm concentration and estimated chromosomal aberrations (r = -0.642), no other correlations were observed. Data on confounders influencing sperm characteristics, such as smoking, occupational or environmental hazards, alcoholism, co-morbidities and other andrological conditions, were not collected. This is the first study to demonstrate that sperm qualitative characteristics in anticancer therapy naïve oligozoospermic TC patients differ significantly from those in IO men and do not differ from those in NZ men. Our results need to be validated in similar groups of men and in other patient groups with cancer where cryopreservation is advisable. This research was supported by the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of TÁMOP-4.2.4.A/2-11/1-2012-0001 'National Excellence Program'. The authors have no conflict of interest to declare.