Testes, like other tissues, depend on a continuous supply of blood to deliver gasses, substrates and chemical effectors for cellular work and the removal of metabolic end products. Disturbances in testicular blood flow cause infertility, and a prolonged elevation in testicular temperature, occasioned by impaired blood flow, places an individual at high risk for testicular cancer. This study tests the hypothesis that local vascular controls operate within the testicular microcirculation to match blood delivery to tissue metabolic demands. Local control over testicular blood delivery ensures an overall steady-state in the organ's blood supply and hence all aspects of testicular performance. The first specific aim is to develop and validate a model system designed to investigate testicular microvessels in situ. No such model exists for the testis, but other tissues are viewed in this fashion. An intravital testicular preparation will be devised to visualize microvessels in situ using transilluminated and epifluorescent microscopy. Validation of this model will include: microscopic studies of testes, steroid production, blood gas determination and microvessel reactivity to vasoactive chemical effectors. The model will then be exploited to establish the design characteristics of the microcirculation. These studies place a premium on establishing anatomical flow pathways and the structural/functional determinants for substrate (oxygen) distribution within testicular microvessels. A final set of studies will chart oxygen tension across the microcirculation and in the intra- and inter-tubular compartments of the testis. Taken together, this work will provide: i) a model system for investigating testicular microvessels, ii) a direct test of the substrate supply hypothesis (e.g. local control over oxygen delivery) and iii) a framework for conceptualizing how the microcirculation operates to match tissue metabolic demands with blood flow and/or substrate delivery within the parenchyma. Answers to these propositions are important for two reasons. First, the results will provide new insights for understanding the dynamic aspects of local microvascular control systems within the testis. Second, they will provide the first link between oxygen delivery and the oxygen requirements of several rate limiting enzymes that direct steroid synthesis, on the one hand, and metabolic activity of germ cells in the avascular seminiferous tubules, on the other.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD020876-01
Application #
3319330
Study Section
Reproductive Biology Study Section (REB)
Project Start
1986-09-01
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1988-08-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Virginia
Department
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
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Costabile, R A; Choyke, P L; Frank, J A et al. (1994) Variability of ischemia during spermatic cord torsion in the rat. J Urol 151:1070-2
Costabile, R A; Choyke, P L; Frank, J A et al. (1993) Dynamic enhanced magnetic resonance imaging of testicular perfusion in the rat. J Urol 149:1195-7
Desjardins, C; Duling, B R (1990) Heparinase treatment suggests a role for the endothelial cell glycocalyx in regulation of capillary hematocrit. Am J Physiol 258:H647-54