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A theoretical model for testis thermoregulation.

Studies going back as far as the early 1920's show that there is a clear relationship between testis temperature and semen quality. The most intriguing question is whether there is a mechanism of thermoregulation which, in the human, maintains testis temperature within certain limits that permit euspermia. Thermoregulation is defined as maintaining some specified (optimum?) temperature plus or minus an error over internal and ambient loss factors. A computer Model has been evolved which contains no regulation or feedback. It appears to predict human testis temperature data gathered in earlier studies. The Model accounts for countercurrent heat exchange in the pampiniform plexus and predicts, with an open loop analysis, that there is no feedback or regulation. As far as thermoregulation is concerned, there appear to be no first-order effects taking place in the human testis. This suggests that ambient temperature changes cause corresponding changes in testis temperature. Also any internal changes in thermal properties such as core temperature variations or variability of the countercurrent heat exchanger will also cause temperature change. Testis temperature as predicted by this Model is the result of the heat energy entering the testis from arterial inflow minus the venous outflow and heat loss from the scrotum. The Model predicts that the heat exchanger will function to provide precooling of arterial blood as external temperatures drop but will fail to precool effectively as temperature rises. This is predicated on the fact that the countercurrent heat exchanger becomes less effective as the temperature gradient across the exchanger becomes smaller and less heat energy is able to be transferred from arterial flow to venous flow. The Model also predicts that any diminution of the heat exchanger mechanism either from reduced venous flow or restricted scrotal heat loss will result in higher testis temperature. Lastly, the Model correctly predicted that febrile patients would experience elevated testis temperature during periods of elevated core temperature. Since more heat energy is available in the arterial blood, more heat energy is delivered to the testis under these conditions. In the human it appears that any internal or external factor causing a temperature change will not trigger or activate a feedback mechanism to control the resulting testis temperature. A major factor in subfertile semen may be the inability to check excessive temperature of the testis which impairs the ability to produce and mature fertile spermatozoa.

Body Temperature↗

Is the testis intraperitoneal?

The relationship of the testis to the peritoneal cavity, and hence its position as an intraperitoneal or extraperitoneal organ, remains controversial. Adult anatomy texts favour an extraperitoneal position during and after testicular descent, whereas journal articles favour an intraperitoneal position. Interestingly, there is no similar debate around the position of the ovary despite the common origin of each as indifferent gonads. Through direct observation and the literature review, we aimed to determine whether the testis should be considered an intraperitoneal or an extraperitoneal organ. The anatomical and embryological literature relevant to human and animal models was reviewed. Direct dissections were made in rats (n=8) during foetal development, postnatally, and in mature animals, allowing comparison of foetus with adult and male with female. The position of the human testis was also recorded in various pathological states. Direct dissection in rats reveals an intraperitoneal testis on a mesorchium during both foetal and postnatal life. Intraperitoneal testes are demonstrated in humans in cases of gastroschisis (where the testis may protrude through the periumbilical defect with the bowel), testicular torsion (where the testis is mobile within the peritoneum), and bell clapper testis (where the testes are identifiable as intraperitoneal). We conclude that the foetal testis is an intraperitoneal organ. In the adult rat the testis remains intraperitoneal. The postnatal human testis is intraperitoneal. The adult human testis is intraperitoneal but may appear extraperitoneal. The apparent discrepancy between the adult testis being intraperitoneal or extraperitoneal is likely to result from differences in the relative size of the tunica vaginalis between infant boys and elderly men.

Animals↗

Experimental testicular teratoma promotes formation of humoral immune responses in the host testis.

The testis is an immunologically privileged site. Very little is known about the factors regulating formation of immune responses elicited by a neoplasm in the testis. We have studied the immune response of the host testis against experimental testicular teratoma in mouse by localizing adhesion molecules (CD106, CD54, CD49d/CD29, CD44, CD18, CD8 and CD4), cytokines (IL-2, IL-4, IL-6, IL-10 and IL-12), T-cell costimulators (CD80, CD86) and the lipid antigen presenting molecule CD1d in the testis of 129/SvJ mice with and without experimental testicular teratoma. The testicular teratomas were induced by grafting male gonadal ridges from 12-day-old 129/SvJ mouse fetuses into testes of adult mice from the same strain. The tumors cultured intratesticularly for 2, 3, 4 and 8 weeks (three animals per time point) were used for immunocytochemistry. CD1d was detected in Sertoli cells and in some degenerated tubules of the host testis surrounding the graft. In the tumor, CD1d was detected in glandular epithelia, smooth muscle and in thin fibers of neural origin. IL-2 was observed in some blood vessels of the host testis and of the tumor and in occasional cell infiltrates around these vessels. Some tubular structures of the tumor were also positive for IL-2. IL-6 was detected in Sertoli cells of the normal testis and in Sertoli cells and in solitaryinterstitial cells as well as in the walls of some blood vessels of the host testis. The reaction for IL-6 was more prominent in the tubules apparently damaged by the growing tumor. In the tumor IL-6 was detected in epithelial structures, muscle cells, in thin fibers of neural origin and in some blood vessels. IL-10 was detected in individual cells in the interstitium and in degenerating tubules of the host testis. In the tumor the epithelial structures were positive for IL-10. The interstitium of the host testis was positive for CD106 and the embryonic testicular cords in the graft were also positive, but the tumor was negative. CD44 and CD18 were observed in some blood vessels and in degenerated tubules of the host testis. In the tumor CD44 and CD18 were occasionally observed in cartilage and in epithelial structures. The results of the present study suggest that cytokine microenvironment in the testis containing neoplastic tissue promotes activation of humoral immune responses. In addition, as the damaged seminiferous tubules expressed increased amounts of two cytokines promoting humoral immune responses, IL-6 and IL-10, it is possible that also in other conditions with damage to the tubules, humoral immune responses predominate.

Animals↗

Cbfa1, an essential transcription factor for bone formation, is expressed in testis from the same promoter used in bone.

Cbfa1 is an essential transcription factor for bone formation, but its transcripts have also been detected in thymus and testis. To elucidate the expression of Cbfa1 in testis, we isolated Cbfa1 cDNA from mouse testis. First we examined the length of the transcripts expressed in mouse testis by Northern hybridization. Using a cDNA probe that can detect both Type-I and Type-II Cbfa1 (Type-I: originally reported as Pebp2alphaA by Ogawa et al.; Type-II: originally reported as til-1 by Stewart et al.), 1.8-kb transcripts were detected in testis, and larger transcripts (6.3 kb and 7.4 kb) in T-cell lines, thymus and bone. Using a Type-II specific probe (bone isoform-specific probe), surprisingly, 1.8-kb testis transcript(s) were detected as well as those (6.3 kb) found in bone. In addition, the transcription start site in mouse testis coincides with one of three start sites identified in bone. These results suggest that the testis transcript is generated from the same promoter of Type-II Cbfa1, which is thought to be active only in osteoblasts and some chondrocytes. Next, to define the difference in length of transcripts, we isolated the Cbfa1 cDNA from mouse testis. Sequence analysis of the cDNA showed that alternative splicing around exon 2 and poly-adenylation within exon 8 occurred in the testis isoform, which produce the smaller transcripts. These data revealed that testis Cbfa1 mRNA is transcribed from same promoter used in bones, but the post-transcriptional regulation is different between testis and skeletal tissues.

Animals↗

Multiple transcripts encoding heme oxygenase-2 in rat testis: developmental and cell-specific regulation of transcripts and protein.

We report for the first time that heme oxygenase-2 (HO-2) expression is regulated by developmental and cell type-specific factors in the testis, and we describe the presence of three unique sizes of HO-2 transcripts in the testis. HO-2, together with HO-1 (HSP32), catalyzes oxidative cleavage of the heme molecule to biliverdin, carbon monoxide, and iron; HO-2 is the major isozyme of the testis. Northern blot analysis was used to demonstrate the presence of five transcripts for HO-2 in rat testis mRNA; they range from approximately 1.3 to approximately 2.1 kg in length with a predominant 1.45-kb message; three of the transcripts, approximately 1.45 kb, approximately 1.7 kb, and approximately 2.1 kg, are unique to testis. The two other transcripts of approximately 1.3 and approximately 1.9 kb are common to every tissue examined, including the testis. Analysis of three distinct cDNAs isolated from rat libraries in phage lambda indicates that all are identical from -37, relative to translation initiation through the coding region to the first of two poly(A) signals previously identified in the HO-2 gene (McCoubrey and Maines, 1994). Upstream of -37, the 5' untranslated sequences of the isolates differ in both length and sequence. Comparison with the genomic sequence suggests that the multiple transcripts arise by splicing of alternative first exons as well as use of alternate poly(A) signals. Northern hybridization with probes specific for the unique portion of each cDNA are consistent with this interpretation. Further, unlike HO-1, HO-2 messages are developmentally regulated; only approximately 1.3- and approximately 1.9-kb transcripts were detected, at minute levels, in the testis RNA of 7-day-old rats. A pronounced increase in total message level was observed by Day 28 postpartum, although the level had not reached the marked amplification seen in the adult testis. Further, the transcript patterns differed when Day 28 and adult testis were compared to Day 7 testis. The very predominant approximately 1.45-kb band and the approximately 1.7- and 2.1-kb bands were absent from Day 7 testis. Heme oxygenase activity and HO-2 protein levels, as assessed by Western blot, reflect the increases at the RNA level. Interestingly, although abundant HO-2 mRNA can be detected by in situ hybridization in spermatogonia, spermatocytes, and spermatids, HO-2 protein was detected, by immunocytochemistry, only in spermatids. These observations demonstrate tissue and cell specificity of HO-2 gene expression and suggest that in the testis, HO-2 expression is regulated at the transcriptional and translational levels.

Animals↗

Intratubular germ cell neoplasia of the contralateral testis in testicular cancer: defining a high risk group.

PURPOSE: We define a group of testis cancer patients who are at high risk for carcinoma in situ of the contralateral testis and, therefore, a second germ cell tumor. MATERIALS AND METHODS: The histology was reviewed in 186 testis cancer patients who underwent contralateral testicular biopsy either because of a history of testicular maldescent or an atrophic contralateral testis (defined as a volume of 12 ml. or less). Testicular volume, semen analysis, serum gonadotropin levels, serum testosterone and estradiol levels were assessed in the majority of patients. RESULTS: Univariate analyses identified contralateral testicular atrophy, low sperm density, young age at presentation and low Johnsen score as factors associated with increased risk of a positive biopsy. A history of maldescent in the absence of atrophy was associated with carcinoma in situ prevalence of only 4%. Multivariate analysis identified only testicular atrophy and age at presentation as independent determinants of a positive biopsy. Testis cancer patients with a small contralateral testis had a 20% and those presenting at age 30 years or younger had a 34% prevalence, respectively, of carcinoma in situ on contralateral testis biopsy (95% confidence interval 20 and 46%, respectively). CONCLUSIONS: Testis cancer patients with an atrophic contralateral testis who present before the age of 31 years are at high risk for carcinoma in situ of the contralateral testis and, therefore, a second germ cell tumor. It is estimated that this group comprises 6% of all testis cancer patients. We predict that a policy of performing contralateral testicular biopsy will produce positive results for carcinoma in situ in a third of these patients and will detect contralateral carcinoma in situ in approximately 40% of all testis cancer patients.

Adult↗

Laparoscopic diagnosis and treatment of nonpalpable testis.

OBJECTIVE: Laparoscopy has become one of the important diagnostic modalities of nonpalpable testis and has been developed and applied in the treatment of this disease. In the present study, we investigated the usefulness of laparoscopy in the diagnosis and treatment of nonpalpable testis. METHODS: Laparoscopy was carried out under general anesthesia on 21 patients (23 testes) from October 1991 to October 1999. If the internal spermatic vessels and vas deferens made their way into the internal inguinal ring, the inguinal canal was dissected with an incision in the inguinal region to look for the testis. Patients with intra-abdominal testis underwent laparoscopic orchiopexy or orchiectomy. If the internal spermatic vessels terminated with a blind end intraperitoneally, making it impossible to identify the testis, the case was judged to be vanishing testis and the operation was finalized without any further examination. RESULTS: In eight of 23 testes (35%), the internal spermatic vessels and vas deferens made their way into the internal inguinal ring. The inguinal region was examined in all the eight testes. Orchiopexy was carried out on two testes and orchiectomy was carried out on six testes. An intra-abdominal testis was detected in eight of 23 testes (35%). Laparoscopic orchiopexy was carried out on seven testes. One-stage orchiopexy was carried out on two of the seven testes and two-stage Fowler-Stephens orchiopexy was carried out on five of the seven testes. Orchiectomy was carried out on the remaining testis. Blocking or lack of the internal spermatic vessels and vas deferens was seen in seven of the 23 testes (30%) and this condition was diagnosed as vanishing testis. CONCLUSION: Laparoscopy for nonpalpable testis is considered to be the most effective technique for diagnosing the presence or absence of the testis and the location of the testis.

Adolescent↗

Effects of unilateral torsion of the spermatic cord on the contralateral testis in human and guinea pig.

The fine structure of the contralateral, so-called unaffected, testis of two of three patients with unilateral testicular torsion revealed varying degrees of abnormalities, apparently related to the time course of the condition. In one patient (H-87) with unilateral torsion of 16 days duration, the contralateral testis revealed various morphological abnormalities. These included abnormal nuclear condensation in spermatids, disappearance of the inner component of the basal lamina, degeneration of the germinal epithelium, and "intermixing" of germinal epithelial cells with peritubular components. In the other patient (H-109) with severe atrophy of one testis as a result of torsion, the contralateral testis revealed abnormalities which included spermatids with degenerating heads and tails within the Sertoli cell cytoplasm near the basal lamina and peritubular thickening accompanied by a greater than usual number of Leydig cells. In guinea pigs with experimentally induced unilateral torsion, abnormal spermatid development was seen in the contralateral testis of those animals in which the affected testis was severely damaged. Moreover, the Sertoli cells exhibited a high degree of phagocytic activity. Fewer abnormal spermatids in the spermatogonial compartment were found in the contralateral testis of the animals which had only moderately altered histology of the affected testis. No fine structural change was noted in the contralateral testis of control or sham operated animals or in those which displayed only minimal damage in the affected testis. This study suggests that unilateral torsion of the spermatic cord resulting in moderate to severe damage to the affected testis may be associated with morphological abnormalities in the contralateral testis.

Adolescent↗

[Heterochronic occurrence of bilateral torsion of appendix testis a case report].

An 8-year-old boy who had undergone excision of the left appendix testis for torsion of the left appendix testis about one and a half years previously was brought to our department on February 18, 1991 because of right scrotal pain of 4 days' duration. Palpation revealed induration with tenderness of the superior portion of the right testicle. A scrotal ultrasonographic tomogram revealed a shadow probably representing an enlarged appendix testis. The patient was diagnosed as having torsion of the right appendix testis. There was refractory pain, and there was possibility of reactive epididymitis. So the patient underwent excision of the right appendix testis, two right appendices testis, which had enlarged to 5 mm in diameter were found, histopathological examination revealed slight bleeding and marked edema of the stroma, which may have been caused by torsion of the appendix testis. Scrotal pain subsided postoperatively. Bilateral torsion of the appendix testis is very uncommon, and our case is the 14th case reported. Torsion of the appendix testis occasionally develops. Torsion of the appendix testis occasionally develops bilaterally. When a small, tender mass at the superior pole of testis, torsion of the appendix testis should be considered.

Child↗

Changes in testicular testosterone and acid and alkaline phosphatase activity in testis and accessory sex organs after induction of varicocele in Noble rats.

The present study was undertaken to determine the effects of surgically induced varicocele on testicular androgen production, seminiferous tubular diameter, and acid and alkaline phosphatase activities in testis and accessory sex organs in adult Noble rats. Testosterone concentrations in plasma and in both left and right testis were estimated in both sham-operated and varicocele-induced rats. The activities of acid and alkaline phosphatase were measured in both left and right testis, seminal vesicle, and ventral prostate gland in varicocele-induced and sham-operated rats. The levels of testosterone in plasma in rats with varicocele were lower than those in the sham-operated rats. The concentration of testosterone in the left testis was lower than that in the right testis in varicocele-induced rats while no such differences were observed in sham-operated rats. The seminiferous tubular diameter in the left testis is reduced in varicocele-induced rats from that in the right testis. In the sham animals, testicular acid phosphatase activity was higher in the left testis than the right, while in varicocele-induced animals, no differences in acid phosphatase activity between left and right testis were observed. In varicocele-created rats, the activity of alkaline phosphatase was higher in the left testis than in the right while no differences in alkaline phosphatase activity between left and right testis in sham-operated rats were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗

Species variation of gonadotropic activity in an in vitro assay measuring androgen formation by carp (Cyprinus carpio) testis with special reference to bioassay of piscine gonadotropins.

The objectives of this study were to establish a suitable and validated in vitro bioassay of piscine gonadotropins (GTHs) by using a carp testis androgen production system and to compare the androgenic responses in such an assay to gonadotropins from various vertebrate species. The testes from mature carp with gonadosomatic indices of 8-30% were used. Androgen production was first compared with respect to methods for preparation of the carp testis (sliced, minced, homogenized, and collagenase-dispersed testis preparations). The time course of androgen formation, the effects of xanthine and theophylline, and other factors on androgen production also were investigated. Theophylline was more effective than xanthine in potentiation of gonadotropin-evoked androgen formation by carp testis. The testis preparations were incubated in medium 199 (pH 7.40) containing 2 mM theophylline with shaking at 100 cycles/min at 25 degrees C for 4 hr. Homogenized testis preparations had limited ability for androgen production, while sliced, minced, and minced-collagenase-dispersed testis preparations were highly responsive to gonadotropins for androgen production. The minced testis preparation, utilizing 100 mg/ml incubation medium per vial, was chosen as the standard incubation procedure in this study. The minced testis androgen production assay was highly sensitive to gonadotropins from several piscine species (silver carp, common carp, and salmon), and all these GTHs produced parallel dose-related androgen production curves. Mammalian GTHs were also capable of promoting androgen formation by carp testis, but they were much less potent than were piscine GTHs. Pregnant mares' serum gonadotropin (PMSG) was more effective than human chorionic gonadotropin (hCG) in evoking carp testis androgen production.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗

An absent testis is associated with contralateral testicular hypertrophy.

Surgical exploration was done in 109 boys ages birth through 9 years with unilateral impalpable testes by physical examination under anesthesia. Of the patients 51 (47%) had an absent testis and 58 had intra-abdominal testes. At open biopsy of the contralateral descended testis the 3 dimensions of the exposed testis were recorded and testicular volume was calculated. The mean volume of the contralateral descended testes of boys with an absent testis was greater than that of boys with intra-abdominal testes at all ages. The differences were significant (p = 0.0019 to 0.0117) from birth through year 4 but not from years 5 through 9. However, the standard deviations ranged from 27 to 74% of the means, and there was broad overlap of the volumes of the 2 groups. These findings indicate that, although the volume of the contralateral descended testis of boys with an absent testis is significantly greater than that of boys with intra-abdominal testes, the volume of the contralateral descended testis is not a reliable criterion for differentiating an absent testis from an intra-abdominal testis in a boy with a unilateral impalpable testis. Surgical exploration continues to be the method of choice for making the diagnosis of an absent testis.

Adaptation, Physiological↗

Immunohistochemical investigations of the autonomous nerve distribution in the testis of the camel (Camelus dromedarius).

The distribution of autonomous nerves in the testis of the camel was studied by immunohistochemical methods. A total of 26 testes was collected during the different seasons of the year. As pan-neuronal markers, antibodies to protein gene product 9.5 and to neurofilaments are superior to antibodies against neuron-specific enolase and acetylcholinesterase histochemistry for the description of the nerves in the camel testis. Testicular nerves reach the camel testis by three access-routes as (1) funicular contribution, (2) mesorchial contribution and (3) as caudal contribution. The main target for testicular nerves is the arterial vascular tree of the organ, whereas all veins of testis and pampiniform plexus are devoid of any innervation in the camel. In the wall of the arteries, the nerves form a plexus at the media-adventitia border. The density of the arterial plexuses increases along the vascular tree: smaller septal and mediastinal arteries are better innervated than albugineal arteries and the latter better than the A. testicularis. The nerves in the septula testis, in the mediastinum and between the Leydig cells show clear seasonal changes, being particularly abundant in autumn and particularly scarce in spring. The nerves that reach the camel testis are unmyelinated and represent in the vast majority postjunctional sympathetic neurons. Cholinergic fibers are absent in the camel testis. Neuropeptide Y is the dominating peptidergic transmitter in the testicular nerves and colocalized with noradrenaline in the same axons. Vasoactive intestinal polypeptide-containing fibers reach the camel testis exclusively as parts of the caudal nervous contribution via the ligamentous bridge between testis and epididymal tail and are restricted to the caudal pole of the testis. Calcitonin gene-related peptide-positive axons are not frequent in the camel testis; nevertheless, they seem to be the most important sensory pathway of this organ.

3-Hydroxysteroid Dehydrogenases↗

Sertoli cells in the boar testis: changes during development and compensatory hypertrophy after hemicastration at different ages.

Changes in Sertoli cell numbers and testicular structure during normal development and compensatory hypertrophy were assessed in crossbred Meishan x White Composite males. Boars were assigned at birth to unilateral castration at 1, 10, 56, or 112 days or to remain as intact controls through 220 days. The first testes removed were compared to assess testicular development. At 220 days, testicular structure was evaluated in boars representing the 25% with the largest (Lg) testis and the 25% with the smallest (Sm) testis in each treatment group. The number of Sertoli cells per testis reached a maximum by Day 56 in Sm testis but not until Day 112 in Lg testis boars, indicating a longer duration of Sertoli cell proliferation in Lg testis boars. Unilateral castration of Lg testis boars on Days 1, 10, 56, and 112 caused the weight of the remaining testis to hypertrophy by 149%, 135%, 119%, and 120%, respectively, and total sperm production to increase to 127%, 128%, 97%, and 106%, respectively. However, Sertoli cell numbers changed little in hemicastrate boars. In Lg testis boars, compensatory hypertrophy primarily involved proliferation of Leydig cells and expansion of existing Sertoli cells with little increase in Sertoli cell numbers, but in Sm testis boars, it involved expansion of existing Leydig and Sertoli cells without increase in cell numbers. These results indicate that Lg and Sm testis boars display intriguing differences during both development and compensatory hypertrophy, and they identify a unique animal model for further studies of factors that program and control Sertoli cell proliferation.

Age Factors↗

Expression and action of neurotropin-3 and nerve growth factor in embryonic and early postnatal rat testis development.

The current study examines the expression and potential actions of neurotropin-3 (NT3), nerve growth factor (NGF), and their receptors during morphological sex determination (seminiferous cord formation) and perinatal rat testis development. The expression of neurotropins and their receptors was analyzed with immunohistochemistry. Cellular localization of neurotropin ligand and receptor proteins changed during embryonic testis development. Neurotropin-3 was localized to Sertoli cells at Embryonic Day 14 (E14), was present in gonocytes at Postnatal Day 0 (P0), and after birth became localized to the interstitium and Sertoli cells (P3-P5). The expression of trk C (the high affinity receptor for NT3) was localized to mesonephric ducts and cells surrounding the cords (E14-E18). In addition, Sertoli cells and preperitubular cells surrounding the cords at E14 also stained for trk C. Neurotropin-3 was expressed in gonocytes and Sertoli cells at P0-P5. Nerve growth factor was detected in Sertoli cells at E14, was clearly in Sertoli and interstitial cells at E16 and E18, and in Sertoli, germ, and interstitial cells from P0-P5. The expression of trk A (the high affinity receptor for NGF) was located in Sertoli and interstitial cells at E16-P5. To determine the actions of neurotropins during embryonic and perinatal testis development, experiments were conducted on E13 and P0 testis. Antisense oligonucleotide experiments with NT3 were used on E13 testis organ cultures to determine effects on seminiferous cord formation. Cord formation was inhibited in 40% of the organ cultures treated with the antisense NT3 oligonucleotides, while no inhibition was observed with sense oligonucleotides. In P0 testis cultures, both NT3 and NGF alone and in combination stimulated thymidine incorporation into DNA. Therefore, the neurotropins are involved in embryonic morphological events (cord formation; NT3) and in growth of the perinatal testis (P0; NT3 and NGF). To define further the growth effects of neurotropins on testis development, expression of transforming growth factor alpha and beta (TGF alpha and TGF beta) were examined in response to neurotropins. The P0 testis cultures were treated with neurotropins, and expression of mRNA for TGF alpha and TGF beta was analyzed utilizing a quantitative reverse transcription-polymerase chain reaction assay. Nerve growth factor and NT3 alone or in combination inhibited expression of mRNA for TGF alpha while NT3 increased mRNA expression of epidermal growth factor receptor. The combination treatment of neurotropins inhibited expression of TGF beta 1 and increase expression of TGF beta 3. In summary, observations suggest that NT3, NGF, trk A, and trk C are localized to cells critical to seminiferous cord formation and appear to be important regulators of morphological sex determination. In addition to these morphological effects, both NT3 and NGF stimulate P0 testis growth and may elicit their action through altering the expression of locally produced growth factors such as TGF alpha and TGF beta. Taken together these results suggest that neurotropins are regulators of paracrine cell-cell interactions that result in morphological sex determination and perinatal testis growth.

Animals↗

Renal and testis injuries in team sports.

PURPOSE: Children with a solitary testis or kidney are generally advised against contact team sport participation to protect the solitary organ. We performed a review of renal and testis injury cases to ascertain if there was an increased likelihood of significant renal or testis injury in team sports. MATERIALS AND METHODS: We retrospectively reviewed charts on patients evaluated and/or admitted to the trauma service with renal or testis injuries. Severity, outcome and external cause of injury were evaluated as well as patient demographics. Patients were excluded from study if there was no radiographic or physical (postmortem or surgical) evidence of injury. Trauma admission/registry data from all patients enrolled were used for comparison. RESULTS: Of 14,763 patients enrolled in the trauma registry from July 1984 until December 2000, 450 (3%) were given a renal or testis injury diagnosis by the registry but only 209 patients (1.4%) met the review criteria for documentation of injury. There were 193 renal injuries (92.3%) and 16 testis injuries (7.7%). A total of 113 injuries were sustained during a recreational or team sport activity (54.1%) and only 10 renal (6) or testis (4) injuries recorded were sustained in team sports (4.8%). Overall team sports injuries recorded in the trauma registry for the study period was 3.4%. No team sports injured patient had a solitary testis or kidney and 1 patient had congenital ureteropelvic junction obstruction. There were only 3 associated injuries (spleen 2, skeletal 1) in the 10 patients. Surgical exploration was performed in all 4 testis injury cases, acute repair of renal injury was done in 1 and delayed pyeloplasty was performed for congenital ureteropelvic junction obstruction. No organs were lost and all patients recovered uneventfully. CONCLUSIONS: Renal and testis injuries occur with team sports, although at a much lower rate than from other external causes of injury. Most patients ultimately do well without loss of the injured organ. Recommendations against team sport participation may not be necessary in patients with a solitary kidney or testis.

Adolescent↗

Carbohydrate moiety of follitropin receptor is not required for high affinity hormone-binding or for functional coupling between receptor and guanine nucleotide-binding protein in bovine calf testis membranes.

Previously, we have extensively studied FSH-receptor interactions using bovine calf testis membranes, and demonstrated that the high-affinity FSH binding to receptors and coupling of FSH receptors with guanine nucleotide-binding protein (Gs protein) in a GTP-sensitive state are important initial events in FSH action. In this study, using the same plasma membrane system, we examined the glycoprotein nature of the FSH receptor and determined the contribution of carbohydrate moieties to these functions of the FSH receptor. Our approach involved enzymic deglycosylation of FSH receptors present in calf testis plasma membranes and then removal of incompletely deglycosylated FSH receptors by lectin affinity chromatography. Following treatment of testis membranes with peptide N-glycosidase, the receptor, as identified by ligand-blot analysis, had a higher electrophoretic mobility indicating a decrease in M(r) from 240-200K. Treatment of testis membranes with neuraminidase caused a reduction (to approximately 225K) in the size of the receptor consistent with desialylation. However, digestion with O-glycosidase (endo-alpha-N-acetylgalactosaminidase) did not affect the mobility of the FSH receptor. These results suggest that bovine testis FSH receptor contains predominantly N-linked oligosaccharide chains, a finding which is consistent with recent predictions that N-linked glycosylation, but not O-linked glycosylation sites are present in cloned FSH receptor from rat testis. Moreover, calf testis membranes after treatment with peptide N-glycosidase F, were solubilized with Triton X-100 under optimum conditions that preserve the physical and functional coupling of FSH receptors with guanine nucleotide-binding protein, and then subjected to lectin affinity chromatography. Scatchard analysis indicated that intact and deglycosylated FSH receptors bound 125I-human FSH with similar affinities. In the presence of GTP, the binding of 125I-human FSH to intact and deglycosylated receptors decreased similarly and in a noncompetitive manner. Treatment of testis membranes with NAD plus cholera toxin, but not NAD plus pertussis toxin, eliminated the GTP effect on FSH binding to enzymic deglycosylated as well as intact receptors, suggesting that the guanine nucleotide binding protein mediating GTP regulation of FSH binding in these membranes is probably Gs protein. Our results suggest that the bovine testis FSH receptor contains predominantly N-linked oligosaccharide chains consistent with recently predicted N-linked glycosylation sites of cloned FSH receptor of rat testis. The bovine testis FSH receptor does not require N-linked carbohydrate for high-affinity hormone binding.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Expression of a novel reticulon-like gene in human testis.

Identification of genes that are specifically expressed in the adult testis or the fetal testis is important for the study of genes related to the development of the testis. In this study, a human testis cDNA microarray was established. PCR products of 9216 clones from a human testis cDNA library were dotted on a nylon membrane; mRNA from adult and fetal testes were purified and probes were prepared by a reverse transcription reaction with testis mRNA as template. The microarray was hybridized with probes of adult and fetal testes, and 96.8 and 95.4% of clones were positive, respectively. In total, 731 clones were differentially expressed: 592 were highly expressed in adult testis and 139 were highly expressed in fetal testis. Among these genes, a new reticulon (Rtn)-like gene was detected and named Rtn-T. Rtn-T was highly expressed in adult human testis. The cDNA of Rtn-T contains 3491 bp and the putative protein had 968 amino acids. This protein is homologous to the six known members of the Rtn family (KIAA0886, Rtn xL, reticulon 4a, Nogo-A, Nogo-A short form, and brain my043) but was different at the 5' end. All homologues originate from one gene, and result from both different promotor regions and different splicing. Rtn-T lacks the first exon and contains a second exon that is lacking in the other homologues. Rtn-T is shorter than KIAA0886, Rtn xL, reticulon 4a and Nogo-A, but longer than the Nogo-A short form and brain my043. Sequence analysis showed that Rtn-T protein has two hydrophobic regions that may be membrane-spanning domains. Expression profiles showed that Rtn-T is specifically and strongly expressed in testis. The results of the present study indicate that the Rtn-T gene is differentially expressed in adult and fetal testes and encodes a membrane protein that may have a function in testis development.

Adult↗