Infertility in men following spinal cord injury (SCI) has been attributed primarily to ejaculatory failure. In addressing this problem, recent advances in electro- and vibratory ejaculation have permitted the routine acquisition of semen from men with SC. However, sperm motility in these ejaculates is generally poor and fertility rates have been low. These observations suggest that SCI may have detrimental effects, yet to be ascertained, on male reproductive function. To better understand the effects of SCI on male reproductive function, we have performed preliminary experiments using the rat as a model to examine perturbations in the structure and function of the male reproductive tract following surgical ablation of specific nerves or nerve plexuses. Our initial studies show that surgical ablation of the inferior mesenteric plexus results in an abnormal accumulation of sperm within the epididymis, changes in epididymal histology and luminal proteins, and reductions in epididymal sperm swimming velocities. Extending these studies, the overall objective of this application is to examine how the loss of innervation affects male reproductive function.
The specific aims are: 1) to determine the contributions of specific nerves to the autonomic innervation of the testis, epididymis and vas deferens; and 2) to examine the effect of surgical denervation on sperm transport and storage in the epididymis and on sperm fertility. To accomplish Specific Aim 1 we will measure the levels of norepinephrine and choline acetyltransferase, markers of sympathetic and parasympathetic innervation, respectively, in the testis, epididymis and vas deferens in untreated rats and after sham operations or after surgical removal of the inferior mesenteric plexus, the hypogastric nerve(s) or the pelvic plexus(es). In supporting studies we will compare, using physiologic organ baths, the amount of nerve-stimulated contractility in the epididymis and vas deferens with or without surgical denervation. Towards accomplishing Specific Aim 2 we will first identify and characterize the site of the denervation-induced functional obstruction within the epididymis observed in our initial studies by labeling the DNA of testicular sperm with [3H] thymidine, then monitoring the migration rate of the [3H] labeled sperm through the epididymis and vas deferens in untreated, sham-operated and surgically denervated rats. Next, we will determine whether the epididymal changes following denervation result in part from the abnormal accumulation of sperm within the epididymis secondary to the induction of a functional obstruction. To address this question, we will determine whether the effects of surgical denervation can be duplicated by partially obstructing the epididymis using jeweler's jump rings, while maintaining innervation - alone or in combination with efferent duct transection to prevent the luminal accumulation of sperm. Finally, we will use intrauterine insemination to determine the effect of denervation on the fertility of epididymal sperm. Taken together, these studies will provide new insights into our understanding of male infertility resulting from SCI and, consequently, provide new awareness regarding reproductive rehabilitation following SCI.
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