Functional Importance of the Vascularization of the Testis and Epididymis for the Maintenance of Normal Spermatogenesis

Transcription

1 Functional Importance of the Vascularization of the Testis and Epididymis for the Maintenance of Normal Spermatogenesis R. G. Harrison, M.A., D.M., B.Ch. THE TREATMENT of male infertility is now recognized as of growing importance, since it has been estimated 22 that defects of the male generative organs are responsible for at least one-third of infertile marriages. But the results of hormone therapy in abnormalities of spermatogenesis, for example, are very disappointing, and only within the last few years has it been found possible to rectify certain developmental abnormalities of the vas deferens. Research on the functional anatomy and development of the male sex organs is therefore of great urgency. The investigation and treatment of male infertility seems, for the time being, to have ceased forward progress,23 and it is desirable that a fresh approach should be adopted. The following studies, by means of an analysis of the vascularization of the testis and epididymis, at least point the way to a better understanding of the relation of testicular function to structure and of the disorders of the testis which may be encountered in sterility. The human testis is unique amongst abdominal viscera in having the longest and thinnest artery. It also differs from the testes in over 50 mammalian species so far studied 6 8 by possessing an artery which is almost straight; the testicular artery in most mammals shows some degree of convolution before reaching the testis, when examined by arteriographic and microarteriographic methods. 10 The convolutions are most marked in the ram and bull (Fig. 1) in which a cone of arterial convolutions is formed in From the Department of Anatomy, University of Liverpool, England. 366

2 Vol. 3, No. 5, 1952] MAINTENANCE OF NORMAL SPERMATOGENESIS 367 the spermatic cord that measures as much as two meters in length when unrolled. The human testicular artery shows the least degree of convolutional complexity (Fig. 2). The artery in various other mammalian species exhibits different degrees of tortuosity between these two extremes (Figs. 3-7). Exceptions are the Marsupialia, in which the artery forms a "rete mirabile" 7 (Fig. 8), and the testiconda, in which the artery passes straight into the testis after a very short course. This remarkable tortuosity of the mammalian testicular artery suggests that there may be some slowing of blood flow to the testis, allowing correspondingly greater heat loss from arterial blood before supplying testicular tissue than would be the case with a straight artery. This would be accentuated by the small caliber of the artery and other already well-known features such as the activity of the dartos muscle; 21 the character of scrotal skin; and the size, shape, position, and intrinsic heat production of the testis. 4 Since the testicular artery differs in degree of tortuosity in different mammals it would be expected that this should be correlated with differences in the abdominotesticular and abdominoscrotal temperature gradient. That this is, in fact, the case is demonstrated by experiments 14 : 15 in which fine copper-constantan thermocouples were used to measure the temperature of the peritoneal cavity, testis, and scrotum in various mammals. The average abdominoscrotal temperature difference is 2.2 C. in man 1 and as much as 13.0 C. in the ram. Between these two extremes the variation of temperature difference in mammals can be correlated with the degree of arterial convolution. Man has a smaller temperature difference than that in seven mammalian species studied, and it is possible that the vascular arrangement in the human testis is less efficiently adapted than that in these. other mammals to maintain the testis at a temperature sufficiently below that of the peritoneal cavity to allow for minor variations in environmental temperature. If this is the case, then it is extremely important that observations should be made on the effects of warm underclothing and repeated bathing at high temperatures on human spermatogenesis. The effect in professional footballers of wearing heavily insulated protective devices over the perineum for extensive periods should be investigated, particularly since such persons also take frequent hot baths. There is already evidence that elevation of environmental temperature has an adverse effect on spermatogenesis. It has been known since the time

3 2 a b 3 4 Fig. 1. Arteriograph of the testis of a young bull following injection with 20 per cent Chlorbismol (a preparation of bismuth oxychloride). Note the marked convolution of the testicular artery both in the spermatic cord and on the surface of the testis.

4 Vol. 3, No.5, 1952] MAINTENANCE OF NORMAL SPERMATOGENESIS 369 of Astley Cooper ( 1830) that the adult cryptorchid is sterile, and the production of th1s condition experimentally inevitably leads to sterility if both testes are rendered cryptorchid. 18 Insulation of the ram's scrotum against loss of heat by wrappmg it securely with layers of woollen material and a waterproof covering leads to degeneration of the testes within eighty days. Moore 19 has shown that continuous application of heat to the scrotum is more destructive for the testis than intermittent, daily application, and wet heat more injurious than dry. Difficulties have also been experienced in the breeding of animals transferred from temperate to hot climates, and this may similarly be related to variations in the pattern of the testicular artery in different species (Figs. 3 and 4). The over-all length and degree of convolution of the testicular artery in Nigerians is significantly greater when examined statistically than in Europeans. 24 The fact that the testis possesses a complicated system of veins arranged as the pampiniform plexus also suggests that this may be accompanied by a complex physiologic mechanism. This anatomic arrangement is better adapted structurally for the "precooling" of arterial blood by venae comites already known to occur in limb vessels. 2 5 Utilization of the methods of the late Professor Bazett 15 has demonstrated that the close relationship of the testicular artery to the surrounding veins of the pampiniform plexus facilitates the exchange of heat between them. Since the testis is at a lower temperature than that of the abdominal cavity, venous blood leaving the testis is at a lower temperature than that in the artery approaching it. Ex- Within the testis can be seen the radial arteries passing towards the central mediastinum. Fig. 2. The arterial supply of the testis of a man aged 35 after injection of the vasal artery, a, with Chlorbismol. The injection medium has filled the testicular artery, b, by the anastomoses between it and the vasal artery, which can be seen at the caudal pole of the testis (on the right in the figure). The testicular artery is seen to reach this part of the testis and then pass up the anterior aspect of the lateral surface of the organ to give off its branches into the testicular parenchyma. Fig. 3. The arterial supply of the testis of the polar bear, Thalarctos maritimus, shown by radiography after injection of the testicular artery with a 20 per cent suspension of bismuth carbonate in normal saline. Fig. 4. The arterial supply of the testis of a brown bear after injection with 20 per cent bismuth carbonate and radiography. Unfortunately there had been some clotting of blood in the artery before injection so that its outline is not well-defined. The convolutions of the artery are easily noticeable, however, and are seen to be more extensive than in the case of the polar bear. The artery also divides into many more branches on the surface of the testis, thus providing a great surface area for radiation of heat.

5 Fig. 5. The arterial supply of the testis of the Lar Gibbon, Hylobates lar, following injection with Chlorbismol and arteriography with a microradiographic apparatus. The relative straightness of the testicular artery can be easily seen. The vasal artery (the thinner vessel on the right of the testicular artery in the figure) is also injected. Note the very marked similarity with the pattern in the human. (X 2) Fig. 6. Arteriography of the testis of a Drill, Mandrillus leucophaeus, after injection with Chlorbismol. Fig. 7. Microarteriograph of the testis of a chimpanzee, Pan Satyrus, after injection with Chlorbismol. The convolution of the testicular artery before reaching the testis is more marked than in most specimens from this species. (X 1.8) Fig. 8. The pattern of the testicular artery in the black wallaby, Macropus bicolor, as seen by radiography after injection with Chlorbismol. The single, undivided artery (at the top of figure) is seen to divide into a number (actually 118) of separate arteries which rejoin to form four vessels at the upper pole of the testis (on the right of the lower part of the figure). These four vessels give off branches and spread out over the posterior surface of the testis.

6 Vol. 3, No. 5, 1952] MAINTENANCE OF NORMAL SPERMATOGENESIS 371 change of heat between the vessels effects "precooling" of arterial blood, and thus enables the temperature of even the center of the testis to be lower than that of the abdominal cavity. A detailed knowledge of the course and distribution of the human testicular artery is also necessary for an appreciation of the results of surgical intervention in the neighborhood of the spermatic cord. The effect on the testis of deliberate or inadvertent ligature of the testicular artery during the operations of herniorrhaphy and radical operation for varicocele is of some consequence for the young male patient. The results of experiments on laboratory animals cannot be applied unconditionally to this problem, for the vascularization of the testis in the dog and rat, for example, differs from that in man. The human testicular artery anastomoses directly with the vasal and cremasteric arteries without the intervention of any of its narrow branches, as in most mammals below the anthropoid level. Further, the sum of the diameters of the cremasteric and vasal arteries in man is at least equal to the diameter of the testicular artery in one-third of cases, while in two-thirds of cases the cremasteric artery enters into functional anastomotic connection with the testicular and vasal arteries. 9 The results accruing from section of only the testicular artery are therefore likely to be favorable in about one-third of patients. Similarly, the interruption of the venous drainage of the testis in radical operation for varicocele will have no effect on spermatogenesis if performed at the level of the internal inguinal ring since the pampiniform plexus is less complicated here and the collateral circulation through the cremasteric and vasal veins would not be impaired. 16 Transient damage to the arterie> supplying the testis during operations in the inguinal region is probablv much more frequent than is generally realized. Kinmonth has described how the dissection of an artery during surgical operations may result in spasm, and that this spasm may persist four hours or days. It has been demonstrated that ischemia of the rat testis of only one hour's duration is sufficient to produce irreparable damaq"e, while less severe ischemia produces appearances in the seminiferous tubules indistinguishable from those found in cases of human infertility. Arterial damage should therefore be avoided during such operations as radical operation for varicocele, and if it should occur recourse should he made to local treatment with papaverinep Quite apart from surgical dam-

7 372 HARRISON [Fertility & Sterility age it is possible that at least some of the degenerative changes found in the testis in cases of infertility may result from ischemia. A detailed knowledge of the course of the testicular artery is very important in the performance of testicular biopsy. Although this diagnostic procedure is simple to pertorm, it is not generally realized that it carries a definite risk of damage to the testicular artery, which can be explained by the inadequacy and, in many cases, inaccuracy of contemporary anatomic descriptions of the course of this artery. Once the artery reaches the mediastinum testis, either as a single or divided channel, it does not pass directly into testicular parenchyma, but first courses on the deep aspect of the tunica albuginea before giving off any branches.h Any incision of the tunica albuginea to procure biopsy material may therefore involve the artery, resulting in partial or complete ischemia of spermatogenic tissue and consequent worsening of the very state the clinician wishes to cure. To avoid damage to the artery, the optimum site for biopsy is the upper third of the lateral surface of the testis, the incision being made transverse to the long axis of the organ. Recent research 12 has indicated that the vascularization of the epididymis is not without some interest in the consideration of sterility. Interruption of vessels supplying the caput epididymidis of the rat leads to the formation of an area of necrosis involving the tubules of this structure; this results in a rapid dilatation of the vasa efferentia, which become blocked by spermatozoa, and a distention of the testis. Histologically the seminiferous tubules are dilated and display appearances very similar to those found in some cases of human sterility; the spermatids show annular clumping of chromatin in their nuclei, for example, and multinucleate spermatids are formed (Fig. 9). These experiments are important for a comprehension of the normal functioning of the testis. They demonstrate that a normal epididymis is necessary for the integrity of the testis, and may explain the "solid" appearance of the epididymis 23 found in some cases of sterility. The late result of the epididymal necrosis is a fibrosis, and the epididymal arteries may be subject to spasm or thrombosis. Apart from the similarity of the arterial supply of the human epididymis to that in the rat, the arteries supplying the human epididymis commonly arise from the testicular artery as far as 3~ inches from the testis; they are, therefore, just as liable to damage in operations in the inguinal region as the testicular artery itself.

8 Vol. 3, No. 5, 1952] MAINTENANCE OF NORMAL SPERMATOGENESIS 373 These researches also demonstrate that there is normally a vis a tergo from the testis along its efferent ductules; the testis, apart from generating spermatozoa, also propels them along the proximal part of its efferent channels. Any blockage of these channels leads to distention of the testis; it is probable, therefore, that the involvement of the testis in the primary Fig. 9. Photomicrograph of a histological section of a rat's testis fourteen days after interruption of the vessels supplying the caput epididymides. The testis had, by this postoperative time interval, become contracted after its preliminary distention. The seminiferous tubule in the top left-hand comer of the figure contains little more than Sertoli cells and many spermatids with crescentic or annular clumping of chromatin in their nuclei. The tubule in approximately the middle of the figure contains four multinucleate spermatids. Portions of other tubules seen in the figure are seen to have lost most of their spermatogenic cells (X 100). stages of an acute epididymo-orchitis is a pure distention rather than an inflammation. Information regarding the features mentioned in this communication results from an approach to a clinical problem by research in the basic medical sciences. These features should be considered in any case of testicular dysfunction not ostensibly caused by hormonal imbalance, and it is hoped that a knowledge of them will facilitate the application of fundamental anatomical principles to the diagnosis and treatment of male infertility.

9 374 HARRISON [Fertility & Sterility REFERENCES 1. BADENOCH, A. W. Descent of the testis in relation to temperature. Brit. M. ]. 2:601, BAZETT, H. C., LovE, L., NEWTON, M., EINSENBERG, L., DAY, R., and FoRSTER, R. E. Temperature changes in blood flowing in arteries and veins in man. Physiol. 1:3, ]. Appl. 3. CooPER, AsTLEY "On the anatomy of the testis." In Observations on the Structure and Diseases of the Testis. London, Longman, Rees, Orme, Brown and Green; 1830, Pt. I, pp CREw, F. A. E. A suggestion as to the cause of the aspermatic condition of the imperfectly descended testis. ]. Anat. 56:98, FoRSTER, R. E., II, FERRIS, B. G., }R., and DAY, R. The relationship between total heat exchange and blood flow in the hand at various ambient temperatures. Am. ]. Physiol. 146:600, HARRISON, R. G. "The blood supply of the testis in relation to problems of sterility." In Conference on Infertility. London, The Family Planning Association, 1948, pp HARRISON, R. G. Vascular patterns in the testis with particular reference to Macropus. Nature, London 161:399, HARRISON, R. G. The comparative anatomy of the blood-supply of the mammalian testis. Proc. Zool. Soc., London 119:325, HARRISON, R. G. The distribution of the vasal and cremasteric arteries to the testis and their functional importance. ]. Anat. 83:261, HARRISON, R. G. "The selection and injection of contrast media," and "The Testis." In BARCLAY, A. E.: Micro-arteriography. Oxford, England, Blackwell, 1951, pp and HARRISON, R. G., and BARCLAY, A. E. The distribution of the testicular artery (internal spermatic artery) to the human testis. Brit.]. Urol. 20:51, HARRISON, R. G., and MACMILLAN, E. W. Unpublished work. 13. HARRISON, R. G., and 0ETTLE, A. G. Pathologic changes in the rat testis following ischaemia. Proc. Soc. Study of Fertility 2:6, HARRISON, R. G., and WEINER, J. S. Abdomina-testicular temperature gradients. ]. Physiol. 107:48, HARRISON, R. G., and WEINER, J. S. Vascular patterns of the mammalian testis and their functional significance. ]. Exper. Biol. 26:304, }AVERT, C. T., and CLARK, R. L. A combined operation for varicocoele and inguinal hernia. Surg., Gynec. & Obst. 79:644, KINMONTH, J. B. The physiology and relief of traumatic arterial spasm. Brit. M. ]. 1:59, MooRE, C. R. Properties of the gonads as controllers of somatic and psychical characteristics: VI. Testicular reactions in experimental cryptorchidism. Am. ]. Anat. 34:269, MooRE, C. R. Properties of the gonads as controllers of somatic and psychical characteristics: VIII. Heat application and testicular degeneration; the function of the scrotum. Am. ]. Anat. 34:331, ETTLE, A. G., and HARRISON, R. G. The histological changes produced in the rat testis bv temporary and permanent occlusion of the testicular artery. ]. Path. & Bact. 64:213, 1952.

10 Vol. 3, No. 5, 1952] MAINTENANCE OF NORMAL SPERMATOGENESIS PHILLIPS, R. W., and McKENZIE, F. F. Res. Bull. Missouri Agric. Exper. Sta., No. 217, SHARMAN, A. Some recent studies and investigations in sterility. ]. Obst. & Gynaec. Brit. Emp. 51:85, WALKER, K. Diagnosis and treatment of male infertility. Proc. Soc. Study of Fertility 2:1, WINSTON, R. M., and HARRISON, R. G. Unpublished work, 1950.