Terry T. Turner

ON UNILATERAL TESTICULAR AND EPIDIDYMAL TORSION: NO EFFECT ON THE CONTRALATERAL TESTIS

It is often stated that unilateral testicular torsion results in damage to the contralateral testis; however, there are a growing number of experimental and clinical papers which suggest this is not so. Conflicting results from experimental studies confuse the issue and may be due, among other things, to some specifics of the experimental model. In the present paper, we have examined bilateral rat testes 30 and 60 days after 720 degrees torsion to determine 1) the effect of unilateral testicular torsion with and without the inclusion of epididymal torsion, 2) the effect of relatively chronic torsion (24 hr., 10 day) versus relatively acute torsion (two hr., four hr.), and 3) the effect of establishing the model using scrotal surgery versus using an abdominal approach. Bilateral testicular histology, testis wt. (gm.), cauda epididymal sperm concentrations (sp./ml.), and cauda sperm motility scores (0-4) were examined. Ipsilateral testicular torsion or testicular plus epididymal torsion of two hr. or four hr. duration significantly reduced (p less than .05) ipsilateral testis weights, sperm concentrations, and motility scores, and disrupted normal tissue histology. Contralateral testicles were not altered. Epididymal ischemia alone produced no significant ipsilateral or contralateral effects. Chronic torsion (one day, 10 days) also destroyed ipsilateral testis function without altering the contralateral testicles. The occult cryptorchidism associated with the scrotal approach to establishing the torsion model had no effect on contralateral testicles. In no group, using either Lewis rats or Sprague-Dawley rats, were contralateral testicles altered by unilateral testicular torsion. These results plus recent clinical reports indicate that contralateral testicular damage due to ipsilateral torsion is hardly a proven phenomenon, let alone a significant factor contributing to male infertility.

Varicocele: reversal of the testicular blood flow and temperature effects by varicocele repair

An experimental left varicocele was created in the adult rat by partial ligation of the left renal vein. A varicocele repair was performed by high ligation of the internal spermatic vein. Testicular blood flow and temperature changes were measured in control and sham animals, animals 30 days after establishment of varicocele and animals 30 days after varicocele repair. There was a statistically significant (p less than or equal to 0.01) bilateral elevation of testicular blood flow and temperature in the varicocele group compared to control and sham groups. Varicocele repair returned these blood flow and temperature values to normal. Average testicular blood flow for control, varicocele, sham varicocele and varicocele repair animals were 29.6 +/- 1, 39.8 +/- 2, 30.7 +/- 1 and 29.8 +/- 1 ml. per min. per 100 gm. tissue, respectively. Testicular temperatures averaged 34.4 +/- 0.1, 35.3 +/- 0.2, 34.4 +/- 0.1 and 34.5 +/- 0.1 degrees C, respectively. It is possible that the elevation in blood flow is associated with the elevation of intratesticular temperature, which is known to impair spermatogenesis. The data support a relationship between the varicocele and potential testicular damage.

Effects of varicocele after unilateral orchiectomy and sympathectomy.

An experimental varicocele was created in the adult rat by partial ligation of the left renal vein. There was a significant bilateral elevation of both testicular blood flow and temperature in the varicocele animals (p less than 0.01). Mean testicular blood flow for control and varicocele animals was 29.6 +/- 1.0 and 39.8 +/- 2.0 ml./min./100 gm. tissue, while mean testicular temperature was 34.4 +/- 0.1 and 35.3 +/- 0.2C, respectively. A left orchiectomy was combined with a left varicocele to determine if the left testis is essential for the right testicular response to a varicocele. Elevation of right testicular blood flow was not altered by left orchiectomy (p less than 0.05); however, right testicular temperature was no longer significantly increased. Mean right testicular blood flow and temperature for this group was 39.0 +/- 1.5 ml./min./100 gm. tissue and 34.2 +/- 0.15C, respectively. A left sympathectomy was combined with a left varicocele to ascertain if the right testicular response to the left varicocele was mediated through a neural pathway. A significant bilateral increase in testicular blood flow was noted with a left sympathectomy alone, and thereby masked the ability to evaluate the right testicular response to the simultaneous left sympathectomy and varicocele. Elevation of right testicular blood flow in response to the left varicocele is independent of the presence of a left testis and any immune response it may stimulate. The role of the sympathetic nervous system as a mediator of the bilateral varicocele effect remains undetermined.

The Rhox5 Homeobox Gene Regulates the Region-Specific Expression of Its Paralogs in the Rodent Epididymis

The mechanisms by which the region-specific expression patterns of clustered genes evolve are poorly understood. The epididymis is an ideal organ to examine this, as it is a highly segmented tissue that differs significantly in structure between closely related species. Here we examined this issue through analysis of the rapidly evolving X-linked reproductive homeobox (Rhox) gene cluster, the largest known homeobox gene cluster in metazoans. In the mouse, we found that most Rhox genes are expressed primarily in the caput region of the epididymis, a site where sperm mature and begin acquiring forward motility. This region-specific expression pattern depends, in part, on the founding member of the Rhox cluster--Rhox5--as targeted mutation of Rhox5 greatly diminishes the expression of several other family members in the caput region. In the rat, Rhox5 expression switches from the caput to the site of sperm storage: the cauda. All Rhox genes under the control of Rhox5 in the mouse epididymis display a concomitant change in their regional expression in the rat epididymis. Our results lead us to propose that widespread changes in the region-specific expression pattern of genes over evolutionary time can be the result of alterations of one or only a few master regulatory genes.

Cytokine Responses to E. coli-induced Epididymitis in the Rat: Blockade by Vasectomy

OBJECTIVES To determine cytokine responses in rat epididymal tissues after retrograde Escherichia coli inoculation of the cauda epididymidis via the intact and obstructed vas deferens. METHODS Adult male Sprague-Dawley rats were divided into 3 groups: bilateral sham vasectomy followed by unilateral sham retrograde inoculation in the vas deferens (group A), bilateral sham vasectomy followed by unilateral retrograde inoculation of E. coli (group B), and bilateral vasectomy followed by left-sided inoculation of E. coli (group C). Three days later, the cauda epididymides and proximal vasa were subjected to histologic examination and assay for 9 cytokines. RESULTS Groups A and C showed no histologic evidence of epididymal inflammation. Group B had leukocyte infiltrates in the inoculated tissue. Cytokine levels in the injected cauda epididymides were low in groups A and C; however, interleukin (IL)-1α, IL-1β, and IL-4 were significantly increased in group B. The 6 other cytokines showed no significant change after E. coli infection though tumor necrosis factor-α, and IL-6 did show strong trends for increase. Contralateral epididymides never showed an inflammatory response. CONCLUSIONS Experimental epididymitis induced by retrograde movement of bacteria in the vas deferens results in different responses by different cytokines. The cytokine responses and the histologically evident inflammation are prevented by vasectomy.

Transepithelial movement of non-polar and polar compounds in male rat reproductive tubule examined by in vivo microperifusion and in vivo micropuncture.

Proluminal movement of 3H-testosterone and 3H-sucrose from peritubular to intratubular fluids of the adult rat testis and epididymis was investigated by using in vivo microperifusion and subsequent micropuncture of seminiferous tubules and caput, corpus, and cauda epididymal tubules. Tubules were perifused with Minimum Essential Medium containing 3H-testosterone or 3H-sucrose. 14C-polyethyleneglycol was included in the perifusion fluid as a marker for contamination of intraluminal fluid by interstitial fluid. Radioactivity of isotopes in perifusion and intraluminal fluids was determined at one and two hours after perifusion and the percentage of peritubular isotopes appearing in intraluminal fluid was determined. Net entry of 3H-sucrose into the seminiferous and epididymal tubules was significantly reduced. Proluminal movement of 3H-androgen across the seminiferous epithelium was also restricted. In contrast, intraluminal 3H-androgen concentrations in caput epididymal fluid were 200 to 300% of those in peritubular fluid at both one and two hours after perifusion. Similar results were found in the corpus epididymidis. 3H-androgen concentrations in cauda epididymal fluid were approximately 125% of peritubular isotope concentrations. The exact mechanism underlying this uphill proluminal movement of 3H-androgen into the rat epididymal lumen remains to be elucidated.

Looking to the Future of Epididymal Research: Why This, Why Now?

Epididymal biology is an area of science at risk. Never a large field to begin with (the number of papers produced by laboratories studying the epididymis is roughly only 20% of the number produced by laboratories studying the testis), it tends to shrink even further in times of funding crisis. This matters because the numbers of laboratories, investigators, and trainees in any area of science affects the number of new people coming into the field, the new ideas that new people can bring, and the number of interested scientists on important grant review panels. How can epididymal biologists face the current challenges? First, great ideas are the key. They prompt compelling hypotheses that can be challenged with interesting experiments. Second, it must be recognized that the past is past. The fact that studies on sperm maturation, epididymal histology, or tubule physiology are significant parts of the past does not mean that they are no longer interesting, but it does mean that truly original questions in those areas will likely be difficult to find. In the real world of competitive science, national granting agencies require applications that clearly answer the questions, why is this of interest and why is it important now? Productive areas of future research may include lumicrine regulation of the epithelium, immunobiology of the epididymis, and cell-cell communication between epididymal epithelial cells and cells in the peritubular/interstitial space.

Testicular Dysfunction With Maldescent—Can Urologists Change This With Earlier Orchiopexy?

CRYPTORCHIDISM: “To fully appreciate the diversity of this congenital disorder, one must concede that it is not a single disease process with a common pathogenesis but a group of commonly recognized clinical abnormalities with multiple causes.” This statement is important for understanding what any single treatment, surgical or otherwise, can do for the cryptorchid testis. This is particularly true regarding concerns about cryptorchidism associated testicular degeneration and the idea that early orchiopexy leads to greater testicular preservation. There are other compelling reasons for positioning the cryptorchid testis in the scrotum such as easier detection of testicular cancer and cosmesis/psychological issues, but preservation of maximum spermatogenesis has continued to be an important issue of clinical concern. For many years patient age at orchiopexy has been related to the degree of testicular degeneration at surgery. This understanding has been carried forward to the thought, more implied than proven, that the structural integrity of the testis at orchiopexy is related to eventual adult fertility. Thus, it has been of urological interest to determine the age at orchiopexy that best preserves testicular structure and, presumably, eventual male fertility. In this issue of The Journal Tasian et al (page 704) recommend that children with cryptorchidism be evaluated for orchiopexy before the age of 6 months. Given the recurring interest in this topic one might reasonably ask, based on the evidence presently available, is it likely that early orchiopexy will have any effect on cryptorchidism associated testicular dysfunction in the meaningful sense of adult fertility? The answer is not really, at least not within the context of modern urology. In the middle of the last century it was common practice to wait until the onset of puberty to perform orchiopexy in the hope that the cryptorchid testis would descend on its own. By the 1970s orchiopexy was being performed in patients closer to 5 years old because it had become accepted that only a minor fraction of still undescended testes would spontaneously descend after the age of 6 months and because of accumulating evidence that increased age at orchiopexy was asso-

Bayard T. Storey: 1932–2017

Friends of Dr. Bayard Storey were saddened to hear of his passing at the age of 84 on the evening of 4 June. Bayard was a scion of Harvard and MIT receiving his Ph.D. in chemistry from Harvard in 1958. He spent the large part of his career at the University of Pennsylvania from which he retired as Professor Emeritus of Reproductive Biology in 1996 after a career of making respected contributions in the areas of sperm energy metabolism, sperm lipid peroxidation, sperm cryopreservation, and the activation of the acrosome reaction. Bayard was known for his wealth of knowledge about the fundamentals of chemistry and biochemistry and how they played their roles in cell biology and physiology. He formerly served on the NIH Reproductive Biology Study section, was on the editorial board of several science journals, and was a past chair of the Gordon Conference on Fertilization and Activation of Development. While advocating especially for the advancement of women in the sciences, he was a promoter of young investigators of any stripe, a devoted mentor to many, and friend to many, many more. His former students and fellows are now spread across the spectrum of andrology from clinical medicine to the laboratory sciences, a result emphasizing the breadth of his influence in andrology, specifically, and in reproductive biology, in general. Recognizing the depth and breadth of Bayard’s contributions, the American Society of Andrology selected him for its Distinguished Andrologist Award for the year 2000. He was known for his ability to discuss scientific details and ask penetrating questions in a range of forums be it a conference room, a hallway, or a dining room, but especially the latter as it allowed everyone to enjoy it all over a glass of wine. Life and literature inform us that the loss of any person is a loss to all, but when a special few depart it leaves a deeper scar, an absence always remembered, always regretted. All who knew Bayard will miss him. All who did not know him missed something special.