ACUTE EFFECTS OF SPINAL CORD INJURY ON SPERM FUNCTION

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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.