Basic research to establish a treatment for asthenozoospermic patients.

建立弱精子症患者治疗方法的基础研究。

基本信息

批准号：
07671725
负责人：
OKADA Hiroshi
金额：
$ 1.41万
依托单位：
Kobe Universuty School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

Purpose : (1) To determine the incidence of reactive oxygen species (ROS) formation by spermatozoa from asthenozoospermic patients and the relationship between ROS formation and sperm motion parameters. (2) To assess the efficacy of in vitro and in vivo pentoxifylline treatment of asthenozoospermic patients whose spermatozoa generated high ROS levels.Materials and Methods : (1) ROS formation by spermatozoa from asthenozoo-spermic patients and fertile volunteers was measured by chemiluminescence. ROS formation by the sperm preparations was investigated without stimulation (steady state) or after stimulation with N-formyl-methionyleucyl-phenylalanine (f-MLP) or phorbol-12-myristate-13-acetate (PMA). (2) Spermatozoa from 15 asthenozoospermic patients, whose spermatozoa produced high levels of ROS at steady state, were treated in vitro with pentoxifylline to determine its effect on ROS generation and sperm motion parameters. (3) These same 15 patients and 18 asthenozoospermic patients whos … More e spermatozoa did not produce ROS at steady state were treated with pentoxifylline at two different dosages (300 mg and 1200 mg/day) to determine its effect on ROS generation, sperm motion parameters and sperm fertilizing ability in vivo.Results : (1) When the steady state ROS formation was detected without stimulation and that was not stimulated by f-MLP,the source of ROS could be attributed to the spermatozoa themselves. (2) Spermatozoa from 15 out of 71 asthenozoospermic patients generated ROS at steady state. These 15 patients were assigned to group A patients. (3) Pentoxifylline decreased ROS generation by spermatozoa from group A patients and preserved the decrease of curvilinear velocity and beat cross frequency for 6 hrs in vitro. (4) For group A patients orally administered pentoxifylline failed to decrease ROS generation by spermatozoa. For group A patients orally administered pentoxifylline had no effect on sperm motility, sperm motion parameters and sperm fertilizing ability at low dosage (300mg/day). It increased motility and beat cross frequency at high dosage (1200mg/day), but had no effect on sperm fertilizing ability in group A patients.Conclusions : Stimulation of sperm preparations with f-MLP can identify the source of ROS generated at steady state. Among asthenozoospermic patients, there was a group of patients (group A) whose spermatozoa produces detectable steady state levels of ROS.For this group, pentoxifylline appeared to be effective for reducing ROS formation and preserving sperm motion parameters in vitro. Orally administered pentoxifylline had no effect at low dosage, however, it increased sperm motility and some sperm motion parameters without altering sperm fertilizing ability at high dosage.Future : Currently, there is no effective treatment for patients with deficient sperm functions, such as idiopathic asthenozoospermia. To develop new treatment strategies, it is important to learn more about the nature of these deficiencies. The present results may provide clues to a therapeutic approach for the treatment of idiopathic male-factor infertility. For the confirmation of these results, a prospective and double-blind clinical trial, dealing with fecundity as the crucial outcome measure, is necessary. Less

目的：（1）确定弱精子症患者精子形成活性氧（ROS）的发生率以及ROS形成与精子运动参数之间的关系（2）评估己酮可可碱治疗弱精子症的体外和体内疗效。材料和方法：(1)来自弱精子症患者和生育力患者的精子形成ROS通过化学发光测量精子制剂的 ROS 形成，在无刺激（稳态）或用 N-甲酰基-甲硫氨酰-苯丙氨酸 (f-MLP) 或佛波醇-12-肉豆蔻酸-13-乙酸酯 (PMA) 刺激后进行研究。 (2) 对 15 名弱精子症患者的精子进行体外处理，这些患者的精子在稳态时产生高水平的 ROS。 (3) 这些相同的 15 名患者和 18 名精子在稳态下不产生 ROS 的弱精子症患者接受了两种不同剂量的己酮可可碱治疗（300 毫克和 1200 毫克）。 /天）测定其对体内ROS产生、精子运动参数和精子受精能力的影响。结果：（1）当(2)71例弱精子症患者中有15例在稳态时产生ROS。 (3) 己酮可可碱减少了 A 组患者精子的 ROS 生成，并保持了曲线速度和搏动交叉频率的降低。体外6小时。 (4)对于A组患者，口服己酮可可碱未能减少精子产生ROS。对于A组患者，低剂量（300mg/次）口服己酮可可碱对精子活力、精子运动参数和精子受精能力没有影响。高剂量（1200mg/天）增加了活力和跳动交叉频率，但对A组精子的受精能力没有影响。结论：用 f-MLP 刺激精子制剂可以识别稳态时产生的 ROS 来源。在弱精子症患者中，有一组患者（A 组）的精子产生可检测到的稳态水平的 ROS。在体外，己酮可可碱似乎能有效减少 ROS 形成并保持精子运动参数，低剂量口服己酮可可碱没有效果，但它增加了精子活力和一些活力。未来：目前，对于精子功能缺陷的患者（例如特发性弱精子症）尚无有效的治疗方法，为了开发新的治疗策略，重要的是要更多地了解这些疾病的本质。目前的结果可能为治疗特发性男性不育症的治疗方法提供线索。为了证实这些结果，进行了一项前瞻性双盲临床试验。生育力作为关键的结果衡量标准是必要的。