ACUTE EFFECTS OF SPINAL CORD INJURY ON SPERM FUNCTION

脊髓损伤对精子功能的急性影响

• 批准号: 3331482
• 负责人: TODD A LINSENMEYER
• 金额: $ 24.06万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3331482
• 关键词: Sertoli cells; acrosin; androgen binding protein; antioxidants; autonomic nervous system; degenerative motor system disease; disease /disorder classification; epididymis; fertility; follicle stimulating hormone; human subject; hyperthermia; ischemia; laboratory rat; male; male reproductive system disorder; messenger RNA; northern blottings; radioimmunoassay; reproductive system pharmacology; sperm motility; spermatogenesis; spinal cord injury; young adult human (21-34)

It is well known that infertility is a common sequela in men with spinal cord injury (SCI). There are two causes of this infertility -- poor semen quality and ejaculatory dysfunction. The problem with ejaculatory dysfunction has largely been solved with use of electroejaculation. However, poor semen quality, particularly sperm motility, continues as an unresolved problem. It is generally accepted that a significant number of SCI men have abnormalities of spermatogenesis as well. There have been no prospective clinical studies of spermatogenesis, sperm motility, or sperm function following SCI. Our preliminary data have shown that spermatogenesis may begin shortly after SCI in rats. Poor semen quality has also been noted 2-4 weeks after SCI in men. Neither clinical nor animal studies have identified mechanisms responsible for these impairments. The broad long-term aim of this proposal is to understand mechanisms underlying testicular-epididymal dysfunction in SCI men and in spinal cord transected rats. Understanding of these mechanisms and their time course is critical to development of interventions to preserve fertility in men with SCI. The first area of investigation is the time course of impaired spermatogenesis and sperm function and factors that affect this time course in both rats and men. Rats subjected to mid-thoracic and sacral spinal cord transection will be studied with the following specific aims: 1)to quantify the time course and severity of spermatogenic injury and sperm motility; 2) to determine if the spermatogenic injury is irreversible over 8 months; 3) to determine which specific spermatogenic cells are most vulnerable over time after transection. Men with recent complete traumatic SCI will be grouped into those with neurologic levels at or above T6, T7 - T11 with intact sacral cord and T12 and below with involvement of the sacral cord, so that each group will be relatively homogeneous in their autonomic nervous system function. Specific aims will be: 1) the time course of spermatogenesis by serial measurement of testicular volume, which is known to correlate well with normalcy of spermatogenesis, 2) the time course of sperm quality by serial evaluation of sperm concentration, motility, morphology, and sperm function. Specific mechanisms of testicular-epididymal injury will be investigated. These include abnormal regulation of testicular blood flow and scrotal hyperthermia in both rats and humans. In rat studies, emphasis will be placed on investigating abnormalities of spermatozoa transport and maturation in the epididymis, as well as abnormal function of the Sertoli cells, which are testicular somatic cells that support spermatogenesis. An understanding of the mechanisms contributing to poor sperm quality in SCI men will form a scientific basis for therapeutic efforts to improve their fertility potential. Finally, even if sperm quality cannot be maintained in chronic SCI men, preservation of sperm quality until SCI men are medically stable and able to undergo electroejaculation would have important clinical significance. Sperm banking, which requires good quality sperm, could then be offered to patients.

众所周知，不孕症是男性脊柱疾病的常见后遗症。 脊髓损伤（SCI）。 造成不孕不育的原因有两个——穷 精液质量和射精功能障碍。 射精问题 通过使用电射精已经很大程度上解决了功能障碍。 然而，精液质量差，特别是精子活力差，仍然是一个问题 未解决的问题。 人们普遍认为，相当数量的 SCI 男性也存在精子发生异常。 有 没有关于精子发生、精子活力的前瞻性临床研究， 或 SCI 后精子功能。 我们的初步数据表明 大鼠脊髓损伤后不久，精子发生可能开始。 精液质量差 男性 SCI 后 2-4 周也有发现。 既不是临床也不是 动物研究已经确定了造成这些现象的机制 损伤。 该提案的广泛长期目标是了解 SCI 男性和 SCI 患者睾丸附睾功能障碍的潜在机制 脊髓横断的大鼠。 了解这些机制及其作用 时间进程对于制定干预措施以保护环境至关重要 SCI 男性的生育能力。 第一个调查领域是时间 精子发生和精子功能受损的过程及其因素 影响大鼠和人类的这个时间进程。 大鼠经受 将研究中胸段和骶段脊髓横断 以下具体目标： 1）量化事件的时间进程和严重程度 生精损伤和精子活力； 2) 判断是否 生精损伤在8个月内不可逆转； 3）确定哪个 随着时间的推移，特定的生精细胞最容易受到伤害 横断面。 最近患有完全创伤性 SCI 的男性将被分为 神经系统水平达到或高于 T6、T7 - T11 且骶骨完整的患者 脊髓和 T12 及以下涉及骶脊髓，以便每个 群体的自主神经系统将相对同质 功能。 具体目标是：1）精子发生的时间过程 通过连续测量睾丸体积，已知这与 与精子发生正常性良好，2）精子的时间过程 通过对精子浓度、活力的系列评估来确定质量 形态学和精子功能。 具体机制 将调查睾丸附睾损伤。 这些包括 睾丸血流调节异常和阴囊高温 老鼠和人类。 在大鼠研究中，重点将放在 研究精子运输和成熟的异常 附睾以及支持细胞功能异常， 是支持精子发生的睾丸体细胞。 一个 了解 SCI 中精子质量差的机制 男性将为改善他们的治疗努力奠定科学基础 生育潜力。 最后，即使精子质量无法维持 对于慢性 SCI 男性，保留精子质量直至 SCI 男性 医学上稳定并且能够进行电射精 具有重要的临床意义。 精子库，需要良好的 然后可以将优质精子提供给患者。