Varicocele, or dilatation of the spermatic vein, occurs in 15-30% of human males and is commonly associated with infertility. The varicosity usually develops in the left spermatic vein only and is not known to occur naturally in other species. An experimental model for left varicocele has been developed in laboratory animals and has been used to study the pathophysiology of varicocele. Initial studies showed that unilateral experimental varicocele did indeed induce bilateral testicular changes in blood flow, temperature, sperm count, and sperm motility, and that conventional surgical repair of unilateral varicocele induced an endocrinopathy leading to bilateral reduction of testosterone secretion, yet the mechanism by which the unilateral lesion induces a bilateral change in physiological parameters, the mechanism by which the endocrinopathy is induced and the mechanism by which varicocele causes the initial increase in testicular blood flow remains unknown. In the present application, studies will be performed to determine if the bilateral testicular response to unilateral varicocele is by a neural or humoral pathway, and to determine the nerve/organ involved in that response. These studies will be done through the use of microsurgery methods and blood flow determinations by the radio-labelled microsphere distribution technique. The application also proposes to investigate whether the bilateral decrease in intratesticular testosterone caused by varicocele is due primarily to changes in the anterior pituitary (secretion of luteinizing hormone (LH) needed to stimulate testosterone synthesis in the testis) or to changes in the testis which desensitizes it to normal LH. These investigators will be done using radioimmunoassays for testesterone and LH, and in vitro studies of pituitary cells in perifusion chambers, as well as in vivo studies of testosterone, and LH secretion in anesthetized animals with experimental varicocele. Finally, the proposal details studies of the testicular vasculature and fluid compartments which will lead to a better understanding of how the primary increase in testicular blood flow occurs after induction of varicocele, how this effects intratubular fluid dynamics, and how these specific varicocele-induced changes respond to traditional varicocele repair. This work will provide new information on the effects of experimental varicocele and is important to our understanding of human varicocele and its effects on human fertility.
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