Microcirculation and the vascular control of the testis.

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The arterial blood supply of the human testicular parenchyma within a testicular lobule demonstrates a segmental organization. In correlation to Leydig cells and seminiferous tubules within such a testicular tissue segment the capillary pathway was subdivided into three parts, namely arterial side inter-Leydig cell capillaries, intramural capillaries and venous side inter-Leydig cell capillaries. The organization, ultrastructure and functional aspects of the human testicular microvasculature were studied in detail. The casting preparation demonstrated a tightly organized vascular network. Computer aided 3-D reconstructions revealed that the capillary pathway in the human testis interconnects Leydig cells and seminiferous tubules. Electron microscopically the endothelial cells (EC) of arterial- and venous side inter-Leydig cell capillaries as well as of intertubular capillaries free of Leydig cells were of the continuous type without fenestrations. The intramural capillaries consisted of non-fenestrated and fenestrated sections. In all cases studied, the fenestrations faced the germinal epithelium. Transcytotic vesicles were numerous in the EC of inter-Leydig cell capillaries and in the non-fenestrated part of intramural capillaries. Leydig cells and Sertoli cells demonstrated immunostaining for vascular endothelial growth factor (VEGF) and its receptors flt-1 and KDR. In agreement with data obtained by RTPCR analyses, human testicular capillaries were negative for VEGF but positive for its receptors. Immunohistochemically Leydig cells and Sertoli cells were also positive for Big-Endothelin and Endothelin-1. Endothelin receptors ЕТ-А and ET-B were localized in Leydig cells while Sertoli cells showed only ЕТ-А immunostaining. Testicular blood vessels and peritubular cells were only positive for ET-B. Androgen receptors could be localized on the arterial side of the human testicular microvasculature and on intramural capillaries, whereas the intralobular veins were negative. In contrast, estrogen receptors were found in all parts of testicular vasculature. From these results we conclude: 1) In the human testis, capillaries interconnect Leydig cell clusters and seminiferous tubules in a serial manner. A part of the capillaries runs in between the layers of the lamina propria and therefore represents the capillarization of human seminiferous tubules. It was presumed that the multilayered lamina propria requires its own capillary supply which may allow a rapid exchange of hormones and other nutritious substances between the microvasculature and the germinal epithelium. 2) VEGF produced and released from Leydig and Sertoli cells could act as a paracrine factor on the testicular microvasculature which possesses VEGF receptors and could modulate the permeability of capillaries in the adult testis, e.g. by fenestration of intramural capillaries. 3) The presence of androgen receptors (AR) and estrogen receptors (ER) on the testicular vasculature indicate that the testicular microvasculature is involved in the local endocrine and paracrine regulation of spermatogenesis. Particularly the presence of AR on the arterial side and on intramural capillaries leads to the assumption that androgens could influence the blood supply to Leydig cells and seminiferous tubules. 4) Leydig cells and Sertoli cells could also influence the blood flow via the potent vasoconstrictor ET-1.