Molnar Z, Mokanszki A, Kassai Bazsane Z, Bhattoa H P, Benyo M, Olah E, Jakab A
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Debrecen, Debrecen 4032, Hungary Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen 4032, Hungary
Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen 4032, Hungary.
Hum Reprod. 2014 Sep;29(9):1866-74. doi: 10.1093/humrep/deu179. Epub 2014 Jul 21.
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.
STUDY DESIGN, SIZE, DURATION: 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.
PARTICIPANTS/MATERIALS/SETTING, METHOD: 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.
LIMITATIONS, REASONS FOR CAUTION: 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.
STUDY FUNDING/COMPETING INTERESTS: 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.
睾丸癌（TC）患者在接受抗癌治疗前，其精液样本的定量和定性特征与年龄匹配的不育少精子症（IO）和正常精子症（NZ）男性是否不同？
与NZ男性相比，TC患者的精子浓度显著降低，估计的染色体数目畸变和核去浓缩无差异，而不育少精子症男性的精子质量特征总体上与TC组以及少精子症TC患者相比显著较差。
TC患者在诊断时精子发生改变。然而，TC患者精液量减少的机制尚不清楚。抗癌治疗可能有性腺毒性副作用，且治疗后的生育能力无法预测。在开始抗癌治疗前，可建议进行冷冻保存以保留生育能力，但关于这些精子中遗传畸变风险的数据尚无。
研究设计、规模、持续时间：这是一项横断面研究，对28例TC患者、20例IO患者和20例年龄匹配的NZ男性的精液进行检查，这些患者均来自德布勒森大学医学与健康科学中心的男科中心和精子冷冻保存实验室。TC患者的精液样本在睾丸切除术后、抗癌治疗前采集。对4年期间招募的TC患者的精液样本进行研究。根据精子浓度，将TC患者分为少精子症TC（TCO）组和正常精子症TC组。为进行统计分析，正常组（NZ + IO）包括非肿瘤性NZ和IO男性。
参与者/材料/场所、方法：按照世界卫生组织指南对射精样本进行评估。透明质酸（HA）结合能力为功能测试。为确定染色体数目畸变，我们使用多色荧光原位杂交。进行苯胺蓝（AB）染色作为核去浓缩标记测试。
比较NZ组和TC组时，性染色体和17号染色体的二体性、二倍体以及估计的染色体数目畸变和AB染色结果未显示任何显著差异，尽管TC组的精子浓度（P < 0.001）和HA结合能力（P < 0.001）较低。与TC患者相比，不育少精子症组的估计染色体数目畸变（P < 0.001）、AB染色（P < 0.001）和HA结合能力（P = 0.019）较低。TCO组在每个检查参数上的结果均显著优于不育少精子症组。在非肿瘤对照组（NZ + IO）中，发现精子浓度与非整倍体率（r = -0.642）、AB染色（r = -0.876）和HA结合（r = 0.842）之间存在显著（P < 0.001）相关性（Spearman秩相关系数 = r）；HA结合能力与非整倍体率（r = -0.678）和AB染色（r = -0.811）相关；非整倍体与AB染色之间存在显著相关性（r = 0.559）。在TC组中，除了精子浓度与估计染色体畸变之间的负相关性（r = -0.642）外，未观察到其他相关性。
局限性、谨慎原因：未收集影响精子特征的混杂因素数据，如吸烟、职业或环境危害、酗酒、合并症和其他男科疾病。
这是第一项证明未接受抗癌治疗的少精子症TC患者的精子质量特征与IO男性有显著差异且与NZ男性无差异的研究。我们的结果需要在类似男性群体以及其他建议进行冷冻保存的癌症患者群体中进行验证。
研究资金/利益冲突：本研究由欧盟和匈牙利国家资助，由欧洲社会基金在TÁMOP - 4.2.4.A/2 - 11/1 - 2012 - 0001“国家卓越计划”框架下共同资助。作者声明无利益冲突。
