Yeung C H, Weinbauer G F, Cooper T G
Institute of Reproductive Medicine of the University, Münster, Germany.
J Androl. 1999 Jan-Feb;20(1):72-9.
Hormonal male contraception requires an induction phase before azoospermia and contraceptive safety are achieved. The nature of spermatozoa that may be ejaculated during this induction phase was studied in a nonhuman primate. The GnRH antagonist Cetrorelix was administered daily to five cynomolgus monkeys to induce testicular regression, and the vehicle was given to five control animals. Within 16 days, the antagonist reduced androgens by 80% in the serum and by 50% in the epididymis. Sperm were obtained by mincing different epididymal regions and were examined for morphology (subjectively) and motility (objectively) after removal of the organs 16 and 25 days after continuous treatment. Spermatozoa entering the epididymis of monkeys undergoing regression differed from those of vehicle-treated controls in their greater susceptibility to disruption during preparation for morphological staining. The acquisition of motility by sperm in the epididymides attached to regressing testes occurred in the same epididymal region as controls but did not achieve the median velocities attained by sperm in controls during epididymal passage. Values for most sperm motion parameters developed as in the controls, and, during epididymal passage, sperm developed resistance to stresses encountered during preparation for morphological analysis. These observations suggest that spermatozoa ejaculated before spermatogenesis ceases may be potentially fertilizing because epididymal maturation continues in an androgen-deprived organ. From these preclinical studies, it can be concluded that in men, applying hormonal contraception precautions against pregnancy must be recommended before azoospermia is induced, since the epididymis can partially compensate for poor-quality sperm produced by a regressing testis even when levels of circulating androgens and tissue androgens are low.
激素男性避孕在实现无精子症和避孕安全性之前需要一个诱导期。在一种非人类灵长类动物中研究了在这个诱导期可能射出的精子的性质。每天给五只食蟹猴注射促性腺激素释放激素(GnRH)拮抗剂西曲瑞克以诱导睾丸萎缩,给五只对照动物注射赋形剂。在16天内,拮抗剂使血清中的雄激素减少80%,附睾中的雄激素减少50%。通过切碎附睾的不同区域获得精子,并在连续治疗16天和25天后取出器官后检查精子的形态(主观)和活力(客观)。进入正在萎缩的猴子附睾的精子与接受赋形剂治疗的对照动物的精子不同,它们在形态染色准备过程中更容易受到破坏。在与萎缩睾丸相连的附睾中,精子获得活力的部位与对照相同,但在附睾通道中未达到对照动物精子的中位速度。大多数精子运动参数的值与对照相同,并且在附睾通道中,精子在形态分析准备过程中对所遇到的压力产生了抵抗力。这些观察结果表明,在精子发生停止前射出的精子可能具有潜在的受精能力,因为附睾成熟在雄激素缺乏的器官中仍在继续。从这些临床前研究可以得出结论,对于男性,在诱导无精子症之前必须建议采取激素避孕措施以防止怀孕,因为即使循环雄激素和组织雄激素水平较低,附睾也可以部分补偿萎缩睾丸产生的质量较差的精子。