The proposed research will test the hypothesis that the steroidogenic and spermatogenic functions of the hamster testis are controlled by vascular mechanisms that modulate capillary perfusion, and thereby regulate the supply-demand ratio for oxygen. We assert that local vascular control mechanisms are a significant determinant of Leydig cell (steroidogenesis) and seminiferous tubule (spermatogenesis) performance because the cell types responsible for these two functions are perfused via separate capillary beds. Each capillary bed is controlled by individual arterioles, so the potential to regulate perfusion and, therefore, the performance of the two functional cell types is great. This proposition is supported by a massive body of indirect evidence derived from biochemical and physiological assessments of testicular function. For example, bursts in Leydig cell oxidative demand are triggered by the episodic discharge of pituitary luteinizing hormone which stimulates oxygen dependent enzyme reactions. Surges in germ cell oxidative demand coincide with mitotic and/or meiotic events that occur within well-defined segments (2-6 mm) of seminiferous tubules. We will test the proposition that vascular regulatory processes intrinsic to the testis directly control steroidogenesis or spermatogenesis by modulating the availability of oxygen, tropic hormones, and substrates. To our knowledge, no single laboratory possessed the skills to assess simultaneously both the functional status of testicular parenchymal cells and the vasomotor regulation of capillary perfusion. This special expertise has now been assembled in our laboratory. Using this expertise, we will examine vasomotor responses and their influences on function when triggered by: i) restricted perfusion pressure or vascular inflow, ii) local metabolic stimuli arising from the selective activation of Leydig cells or seminiferous tubules, and iii) electrical stimulation of the spermatic nerve. Each stimulus will be examined to determine its potential to regulate arteriolar tone, to limit or promote the differential perfusion of the dual capillary beds, and to selectively alter the performance of Leydig cells or the seminiferous epithilium in of adult hamsters. The proposed studies develop new concepts to explain the regulation of Leydig cell function and spermatogenesis by mechanisms intrinsic to the terminal vascular bed. This work has special importance to human reproductive health because it provides a framework for investigating the unknown etiology of testicular vascular disorders (varicocele, orchitis, and cryptorchidism), the most prominent source of testicular dysfunction and infertility.
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