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Myofibroblastic pseudotumor mimicking epididymal sarcoma. A clinicopathologic study of three cases.

The clinical and pathologic features of three cases of epididymal pseudotumor are described with emphasis on its differential diagnosis and histopathogenesis. The first lesion was found histologically worrisome in the region of ductus epididymis by a torsioned testis in an 8-month-old boy, although the lesion was clinically indistinctive, and grossly not remarked. Histodiagnostic difficulties are encountered because this lesion forms numerous infiltrative spindle cells in haphazard arrangement. Ultrastructurally, the cell components of this lesion are predominantly myofibroblasts, intermediate cells between fibroblasts and myocytes. Similar epididymal lesions with the same cell components were identified in the two other infantile cases on the review of 36 consecutive orchiectomy specimens all obtained for testicular torsion. These three boys were found to present with a relatively gradual clinical course of the testicular torsion. It is suggested that myofibroblastic proliferation in the epididymal location histologically reminiscent of sarcomas occurs under ischemic circumstances.

Diagnosis, Differential↗

Disruption of testicular steroidogenesis and epididymal function by inhaled benzo(a)pyrene.

The objective of this study was to evaluate the effect of sub-acute exposure to inhaled benzo(a)pyrene (BaP) on testicular steroidogenesis and epididymal function in Fisher 344 rats. Animals were assigned randomly to two control groups and one experimental group for each exposure regimen. Treatment consisted of sub-acute exposure of rats via inhalation to 25, 75, and 100 microg BaP/m(3), 4 h daily for 10 days. Control animals were either exposed to carbon black (CB; sham) to control for inert BaP carrier or they remained unexposed (UNC). Blood samples were collected immediately after the cessation of exposures (time 0) and at 24, 48, and 72 h post-cessation of exposure, to assess the effect of bioavailable BaP on systemic testosterone and luteinizing hormone (LH) concentrations by radioimmunoassay (RIA). Progressive sperm motility of stored sperm (cauda epididymal sperm) was determined microscopically, while density of stored sperm was determined by hemocytometric counting. Progressive motility of stored sperm was reduced in rats exposed to 75 and 100 microg BaP/m(3) compared with their counterparts that were exposed to 25 microg BaP/m(3) or controls. Plasma testosterone concentrations declined as a result of exposure of rats to 75 microg BaP/m(3) from 0 to 48 h post-termination of exposure compared with controls (P<0.05; treatment x time interaction). This decrease was followed subsequently by a compensatory increase in the plasma concentrations of this steroid at 72 h post-cessation of exposures compared with previous time periods and controls (P<0.05). Increases in the mean plasma LH concentrations were observed in rats exposed to 75 microg BaP/m(3) compared with controls, throughout the time periods studied (P<0.05; treatment x time interaction). These data suggest that sub-acute exposure to inhaled BaP contributes to reduced testosterone concentrations and consequently impaired epididymal function of exposed animals.

Administration, Inhalation↗

Psoriatic arthritis associated with adult polycystic kidney disease, seminal vesicle, and epididymal cysts.

Patients with seminal vesicle and epididymal cysts are mostly asymptomatic. To date, only one patient presenting with bloody ejaculate and acute scrotum has been reported. Different extrarenal manifestations and the association of adult polycystic kidney disease (APKD) with some connective tissue diseases are known. We report on a 60-year-old male patient with bloody ejaculate and acute scrotum who had been diagnosed as having APKD 1 year earlier and whose past medical history revealed inflammatory low back pain, psoriasis, and the diagnosis of psoriatic arthritis. Cultures of urine and ejaculate were sterile, and the patient's renal functions were normal. Ultrasound showed epididymal and seminal vesicle cysts in addition to hepatic and renal cysts. Our case is the first in which psoriatic arthritis accompanied APKD, seminal vesicle cysts, and epididymal cysts. We also review other APKD cases that have accompanied seminal vesicle cysts.

Journal Article↗

Performing testicular or epididymal sperm retrieval prior to the injection of hCG.

PURPOSE: Our purpose was to determine the feasibility and efficacy of performing testicular or epididymal sperm retrieval prior to the injection of human chorionic gonadotropin (hCG). METHODS: This report deals with 87 sperm-positive percutaneous epididymal sperm aspiration (PESA), percutaneous testicular sperm aspiration (PTSA), or testicular sperm extraction (TESE) cycles. All sperm retrieval procedures were performed prior to administration of hCG to the women. Retrieved spermatozoa were cultured in vitro in simple medium for approximately 40 hr prior to intracytoplasmic sperm injection. RESULTS: In all but one cycle in which TESE was performed for nonobstructive azoospermia, motile sperm were available for ICSI. The overall fertilization rate was 53%. Pregnancy rate per transfer and implantation rate per embryo were 41.2 and 15.7%, respectively. CONCLUSIONS: Satisfactory fertilization and pregnancy rates can be achieved when PESA, PTSA, or TESE is performed prior to the injection of hCG followed by in vitro culture of spermatozoa approximately 40 hr before ICSI. Scheduling of testicular or epididymal sperm retrieval cases in this way appears to ease the workload on laboratory and operating room personnel. Furthermore, withholding hCG when sperm is absent may obviate the unnecessary risk of ovarian hyperstimulation when spermatozoa cannot be retrieved.

Biopsy↗

Chromosome analysis of epididymal and testicular spermatozoa in patients with azoospermia.

Azoospermic patients can now father children once spermatozoa have been retrieved from the epididymis or the testis. However, there are concerns about the risk of chromosomal abnormalities since an increase in sperm aneuploidy rate has been reported in samples from patients with abnormal sperm parameters. The purpose of this study was therefore to evaluate the sperm aneuploidy and diploidy rates for chromosomes 8, 12, 18, X and Y in spermatozoa extracted from the epididymes (n=10) or the testes (n=6) of patients with azoospermia. Ejaculated spermatozoa of healthy men (n=14) served as control. Epididymal and testicular spermatozoa had an aneuploidy rate significantly higher than that found in ejaculated spermatozoa. The aneuploidy and diploidy rates of testicular spermatozoa were higher, but not significantly different, than those found in epididymal spermatozoa. This study has shown that azoospermic patients have an increased sperm aneuploidy rate. They should therefore be given appropriate genetic counselling before entering in-vitro fertilisation programs.

Adult↗

Epididymal expression of the forkhead transcription factor Foxi1 is required for male fertility.

An essential aspect of male reproductive capacity is the immediate availability of fertilization-ready spermatozoa. To ensure this, most mammals rely on post-testicular sperm maturation. In epididymis, germ cells are matured and stored in a quiescent state that readily can be altered to produce active spermatozoa. This depends on active proton secretion into the epididymal lumen. We have identified Foxi1 as an important regulator of gene expression in narrow and clear cells-the major proton secretory cells of epididymal epithelia. Foxi1 appears to be required for the expression of the B1-subunit of the vacuolar H+ -ATPase proton pump and for carbonic anhydrase II as well as the chloride/bicarbonate transporter pendrin. Using transfection experiments, we have identified a Foxi1 binding cis-element in the ATP6V1B1 (encoding the B1-subunit) promoter that is critical for reporter gene activation. When this site is mutated to eliminate Foxi1 binding, activation is also abolished. As a consequence of defect Foxi1-dependent epididymal sperm maturation, we demonstrate that spermatozoa from Foxi1 null males fail to reach the female genital tract in sufficient number to allow fertilization.

Animals↗

Degradation of insulin in vitro by liver and epididymal adipose tissue from obese-hyperglycaemic mice.

The insulin-degrading activity of liver supernatants and epididymal adipose-tissue homogenates from genetically obese-hyperglycaemic mice (ob ob) and their lean litter mates was studied by measurement of radioactive trichloroacetic acid-soluble degradation products of the insulin molecule. Optimum assay conditions for the decomposition of the hormone were devised. The properties of the degrading activity suggested the presence of enzymic insulin destruction in both the liver and epididymal adipose tissue. There was no difference in insulin degradation in liver samples from obese and lean mice when the results were related to the protein content of the supernatants. The epididymal adipose-tissue homogenates from obese mice displayed about eightfold higher degrading activity per unit of protein than did homogenates from lean animals. The physiological significance of this finding is discussed in the light of the increased fat depots, hyperphagia, raised serum insulin concentrations and increased insulin tolerance previously recorded in this strain of mice.

Adipose Tissue↗

Activity and androgenic control of glycolytic enzymes in the epididymis and epididymal spermatozoa of the rat.

1. Procedures were developed for the extraction and assay of glycolytic enzymes from the epididymis and epididymal spermatozoa of the rat. 2. The epididymis was separated into four segments for analysis. When rendered free of spermatozoa by efferent duct ligation, regional differences in enzyme activity were apparent. Phosphofructokinase, glycerol phosphate dehydrogenase and glucose 6-phosphate dehydrogenase were more active in the proximal regions of the epididymis, whereas hexokinase, lactate dehydrogenase and phosphorylase were more active in the distal segment. These enzymes were less active in the epididymis of castrated animals and less difference was apparent between the proximal and distal segments. However, the corpus epididymidis from castrated rats had lower activities of almost all enzymes compared with other epididymal segments. 3. Spermatozoa required sonication to obtain satisfactory enzyme release. Glycolytic enzymes were more active in spermatozoa than in epididymal tissue, being more than 10 times as active in the case of hexokinase, phosphoglycerate kinase and phosphoglycerate mutase. 4. The specific activities of a number of enzymes in the epididymis were dependent on the androgen status of the animal. These included hexokinase, phosphofructokinase, aldolase, glyceraldehyde phosphate dehydrogenase, phosphoglycerate kinase, pyruvate kinase, glycerol phosphate dehydrogenase, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and phosphorylase. 5. The caput and cauda epididymidis differed in the extent to which enzyme activities changed in response to an altered androgen status. The most notable examples were hexokinase, phosphofructokinase, aldolase, phosphoglycerate kinase, 6-phosphogluconate dehydrogenase and phosphorylase.

Animals↗

Role of Ca2+ ions in the regulation of intramitochondrial metabolism in rat epididymal adipose tissue. Evidence against a role for Ca2+ in the activation of pyruvate dehydrogenase by insulin.

The sensitivity of rat epididymal-adipose-tissue pyruvate dehydrogenase phosphate phosphatase, NAD+-isocitrate dehydrogenase and 2-oxoglutarate dehydrogenase to Ca2+ ions was studied both in mitochondrial extracts and within intact coupled mitochondria. It is concluded that all three enzymes may be activated by increases in the intramitochondrial concentration of Ca2+ and that the distribution of Ca2+ across the mitochondrial inner membrane is determined, as in rat heart mitochondria, by the relative activities of a uniporter (which transports Ca2+ into mitochondria and is inhibited by Mg2+ and Ruthenium Red) and an antiporter (which allows Ca2+ to leave mitochondria in exchange for Na+ and is inhibited by diltiazem). Previous studies with incubated fat-cell mitochondria have indicated that the increases in the amount of active non-phosphorylated pyruvate dehydrogenase in rat epididymal tissue exposed to insulin are the result of activation of pyruvate dehydrogenase phosphate phosphatase. In the present studies, no changes in the activity of the phosphatase were found in extracts of mitochondria, and thus it seemed likely that insulin altered the intramitochondrial concentration of some effector of the phosphatase. Incubation of rat epididymal adipose tissue with medium containing a high concentration of CaCl2 (5mM) was found to increase the active form of pyruvate dehydrogenase to much the same extent as insulin. However, the increases caused by high [Ca2+] in the medium were blocked by Ruthenium Red, whereas those caused by insulin were not. Moreover, whereas the increases resulting from both treatments persisted during the preparation of mitochondria and their subsequent incubation in the absence of Na+, only the increases caused by treatment of the tissue with insulin persisted when the mitochondria were incubated in the presence of Na+ under conditions where the mitochondria are largely depleted of Ca2+. It is concluded that insulin does not act by increasing the intramitochondrial concentration of Ca2+. This conclusion was supported by finding no increases in the activities of the other two Ca2+-responsive intramitochondrial enzymes (NAD+-isocitrate dehydrogenase and 2-oxoglutarate dehydrogenase) in mitochondria prepared from insulin-treated tissue compared with controls.

Adipose Tissue↗

Intracytoplasmic sperm injection using surgically retrieved epididymal and testicular spermatozoa in cases of obstructive and non-obstructive azoospermia.

This was a retrospective study of 115 patients who underwent 124 cycles of ICSI using surgically retrieved spermatozoa. The objective was to compare the results of ICSI in patients with obstructive azoospermia using epididymal spermatozoa (36 cycles) or testicular spermatozoa (58 cycles) with ICSI in patients with non-obstructive azoospermia using testicular spermatozoa (30 cycles). When epididymal spermatozoa were used for ICSI, the fertilization rate per injected metaphase-II oocyte and the clinical pregnancy rate per ICSI cycle were 60.4 and 25%, respectively. When testicular spermatozoa were used in obstructive cases, the fertilization rate and pregnancy rate were 57.9 and 34.5%. In non-obstructive cases the fertilization and pregnancy rates were 41.2 and 16.6%. When patients with obstructive azoospermia were regrouped according to the cause of obstruction, the fertilization and pregnancy rates were 59.1 and 35.1% in acquired obstruction and 58.7 and 24.3% in congenital obstruction. The fertilization and pregnancy rates were not statistically different (p > 0.05) when testicular or epididymal spermatozoa were used in obstructive cases; neither was statistically different (p > 0.05) when compared in patients with congenital and acquired obstruction. On the other hand, the fertilization and pregnancy rates in cases with non-obstructive azoospermia were significantly lower (p < 0.05) than in obstructive cases.

Adult↗

Extra-epididymal spermatozoa express nuclear abnormalities.

Extra-epididymal spermatozoa account for approximately a third of all spermatozoa found in the normal human ejaculate. Whilst remaining outside of the testes at core body temperature, the functional competence of spermatozoa, including cell motility and fertilizing capacity, diminishes. By examining spermatozoa found in the seminal fluid of recently vasectomized men, this study has investigated the nuclear changes that occur in spermatozoa whilst persisting in sites distal to the epididymis. Spectral recordings of spermatozoa stained with the nucleic acid dye, toluidine blue and the sperm chromatin structure assay (SCSA) were performed. Toluidine blue staining of human sperm DNA is an effective predictor of abnormal protamine disulphide crosslinking and chromatin condensation. Using flow cytometry, the SCSA determines the sensitivity of sperm DNA to acid-induced denaturation, providing a measure of chromatin and DNA damage. Abnormal protamine disulphide crosslinking and chromatin condensation was significantly higher in spermatozoa from patients after vasectomy when compared to normozoospermic controls (p < 0.01). Additionally, spermatozoa from vasectomized donors were significantly more sensitive to acid-induced denaturation than were normozoospermic donors (p < 0.05). The results indicate that spermatozoa surviving in extra-epididymal sites are more likely to possess DNA and chromatin abnormalities than those present in the testes and epididymis. These changes may partly explain the depletion of cell viability and fertilizing capacity of extra-epididymal spermatozoa which has been reported previously.

Cell Nucleus↗

Comparison of polidocanol and tetracycline in the sclerotherapy of testicular hydrocele and epididymal cyst.

OBJECTIVE: To compare the effects and side-effects of polidocanol and tetracycline when used as sclerosants for testicular hydrocele and epididymal cyst. PATIENTS AND METHODS: Forty-five men (median age 67 years, range 42-81) with 46 hydroceles or epididymal cysts were assessed. After puncture and aspiration, the empty sac was instilled with either polidocanol or tetracycline, assigned randomly. Patients recorded any treatment-associated pain on a visual analogue scale. RESULTS: At 9 months of follow-up, nine of 17 men were cured after sclerotherapy with polidocanol compared with 17 of 20 men treated with tetracycline (P < 0.05). Tetracycline produced some pain for 3 days after treatment while polidocanol therapy was almost pain-free. Re-instillation should be considered for recurrences. At the follow-up after 35 months, 16 of 18 men treated with polidocanol and 20 of 22 men treated with tetracycline were satisfied with the outcome. CONCLUSION: Both polidocanol and tetracycline are useful sclerosants for treating testicular hydrocele and epididymal cyst. We prefer polidocanol as a first choice in older patients because there were few short-term side-effects.

Adult↗

Frozen-thawed epididymal sperm is effective for intracytoplasmic sperm injection: implications for the urologist.

OBJECTIVE: To evaluate the pregnancy potential of frozen-thawed surgically retrieved epididymal sperm when used with intracytoplasmic sperm injection (ICSI). PATIENTS AND METHODS: From August 1994 to January 1997, 20 thawed samples of sperm from 19 patients, surgically retrieved and frozen after percutaneous or open epididymal aspiration, were used for ICSI. The results were compared with those obtained using fresh sperm obtained at the same procedure. RESULTS: Of the specimens of surgically retrieved sperm which had been frozen, stored and thawed, 15 had sufficient motile sperm for use with ICSI. The fertilization, cleavage and pregnancy rates in those cycles were similar to the same couples' previous cycle using fresh sperm from the same collection and to the overall results in the NURTURE ICSI programme obtained with fresh epididymal sperm. CONCLUSION: Scrotal exploration for diagnostic testicular biopsy and/or reconstructive surgery without having access to sperm-freezing and storage facilities could represent a lost opportunity for the patient.

Adult↗

Testicular and epididymal sperm numbers and related parameters in the developing awassi ram.

Testicular parameters, parenchymal spermatid concentration, and epididymal sperm reserves were measured in tracts obtained from 16 Awassi rams classified into three age groups (1, 1.5 and 2.5 years old). Between 1 and 2.5 years of age the paired testis weight increased from 164.9 to 315.2 g, the testicular spermatid number (X 10(9)) increased from 15.9 to 55.8, and the total epididymal sperm reserves (X 10(9)) increased from 11.1 to 98.8. Significant correlations were found between the paired testis parenchyma weight and all testicular dimensions and size. Testicular spermatid numbers and concentration were correlated with paired testis weight (r = 0.91 and 0.63), paired testis volume (r = 0.92 and 0.64) and all testicular measurements, particularly paired length X depth (r = 0.92 and 0.66). Regression coefficients between all parameters were essentially linear and highly significant, allowing accurate predictions of testis weight, volume and spermatid numbers to be made. The total epididymal sperm reserves and the sperm content of each of the caput, corpus and cauda of the epididymis were correlated with the paired weights of the epididymis (r = 0.73, 0.75, 0.73 and 0.70), the testis (r = 0.76, 0.83, 0.91 and 0.72), the total spermatid numbers in testicular homogenates (r = 0.70, 0.85, 0.91 and 0.64), and spermatid concentration (r = 0.56, 0.75, 0.72 and 0.49). The storage capacity of the cauda epididymides appeared to develop more slowly than the rate of sperm production because at 2.5 years of age it was about 1.5 and 2.8 times that in rams aged 1.5 and 1 year respectively.

Age Factors↗

Biochemical parameters regulating forward motility initiation in vitro in goat immature epididymal spermatozoa.

An investigation was carried out to analyse the biochemical parameters influencing forward motility (FM) initiation in vitro in the goat caput-epididymal immature spermatozoa. Forward motility was induced in approximately 55% of caput-sperm upon incubation in an alkaline (pH 8.0) modified Ringer's solution containing theophylline (30 mM) (an inhibitor of cyclic AMP phosphodiesterase), dialysed epididymal plasma (EP) and bicarbonate. Both EP and bicarbonate induced sperm motility in a dose-dependent manner, and at saturating doses EP (0.6 mg protein mL(-1)) and bicarbonate (25 mM) induced FM in approximately 38% and 44% of the cells, respectively. The motility-promoting efficacy of EP was attributed to a heat-stable protein termed 'forward motility protein' (FMP). Bicarbonate served as an initiator as well as a stabilizer of FM and its action was not dependent on FMP. FMP can induce FM in the caput-sperm, but it is not essential for sperm motility initiation. Alteration of the medium pH from 6.60 to 8.00 caused a marked increase in the EP or bicarbonate-dependent sperm FM initiation, as well as intrasperm pH. At the physiological pH, bicarbonate served as a much more potent motility activator than FMP, although both the motility promoters showed maximal efficacy at alkaline pH (approximately 7.8). EP as well as bicarbonate elevated the intrasperm cyclic AMP level. Unlike EP, bicarbonate is capable of increasing intrasperm pH. The intrasperm pH increased from 6.54 +/- 0.02 to 6.77 +/- 0.03 during sperm transit from caput to cauda. The data are consistent with the view that FMP activates sperm forward motility by enhancing the intrasperm cyclic AMP level and that extracellular bicarbonate and pH play a vital role in the initiation of sperm FM during the epididymal transit.

Animals↗

Alteration of goat sperm ecto-phosphoprotein phosphatase activity and its distribution on the sperm surface during epididymal maturation.

Phosphoprotein phosphatase (ecto-PPase) of goat epididymal sperm outer surface showed a significant increase in its activity at the initial stage of epididymal sperm maturation (up to the proximal corpus region) followed by a sharp fall towards the terminal phase of the maturation event. PPase activity showed nearly the same profile when estimated in intact cells as well as in isolated sperm plasma membrane. The ecto-PPase was purified to apparent homogeneity by using various biochemical fractionation procedures, such as solubilization with Triton X-100, sephadex gel filtration chromatography, concanavalin A-sepharose affinity chromatography and diethylaminoethyl-cellulose ion-exchange chromatography. The isolated PPase has a molecular mass of approximately 36 kDa and an isoelectric point of 5.95. Sperm surface topography of the enzyme was investigated using fluorescein isothiocyanate-conjugated antibody of the purified PPase. The immunofluorescent studies have demonstrated that the isolated PPase is localized on the external surface of viable sperm. Immunocytochemical studies also revealed a marked topographical alteration of ecto-PPase during epididymal transit of the male gametes. Immunoreactivity was observed all over the surface of caput sperm, but was restricted primarily to the anterior tip of the head in the corpus sperm and to the posterior part of the head in cauda sperm cells. The maturation-dependent decrease in PPase activity was also confirmed by immunofluorescent studies. This remarkable maturation-dependent modification of ecto-PPase activity, as well as its distribution on sperm surface, suggest that the ecto enzyme may play an important role in sperm function by regulating the phosphorylation states of the membrane-associated and reproductive fluid phosphoprotein substrates.

Animals↗

No alpha-lactalbumin-like activity detected in a low molecular mass protein fraction of rat epididymal extract.

The same low M(r) protein fraction of epididymal luminal fluid as that studied previously by Hamilton in 1981 was assayed for alpha-lactalbumin (alpha-lac) activity with bovine milk galactosyltransferase (GalTase) as the enzyme source and bovine serum albumin (BSA) to make the total protein concentrations of all the samples in each assay constant. No alpha-lac activity could be detected in this fraction. When glucose was used as an acceptor, radioactivity passing through the ion exchange column used to retain the remaining UDP-galactose did increase with the amount of the proteins of the low M(r) fraction, but this increase was observed not only for samples with an acceptor but also for samples without. The increased radioactive product co-migrated in high-voltage electrophoresis with galactose, not lactose. When GlcNAc was used as an acceptor, the situation was the same, and the increased radioactive product co-migrated with galactose, not LacNAc. No inhibition of bovine milk GalTase activity by the low M(r) proteins was observed. Addition of protein, either BSA or the low M(r) fraction of epididymal luminal fluid, to assay medium that contained no proteins other than GalTase enhanced the GalTase activity both in forming lactose in the presence of glucose and also LacNAc in the presence of GlcNAc. It appears that the earlier reports of alpha-lac-like activity in epididymal fluids and extracts may have been due to the presence of enzymes liberating free galactose from UDP-galactose and/or a stimulatory non-specific effect of the protein in the solutions on the lactose synthesis activity of the GalTase.

Animals↗

Maturation-related changes in distribution of lectin receptors in baboon (Papio anubis) spermatozoa during epididymal maturation.

Changes in distribution of surface glycoproteins in baboon sperm were studied by lectin blotting techniques. In baboon, several changes in sperm surface occur during epididymal passage. These changes include increased staining of band that was observed with the WGA binding glycoproteins of 140, 80, 52, and 46 kDa; Con A bands of 66, 37, and 26 kDa; and the PNA binding glycoprotein of 114 kDa. A second change was the loss of preexisting band that was observed with RCA binding glycoproteins of 120, 80, 58, 53, 46, and 37 kDa; and the Con A band of 80 kDa. A final change was noted with Con A binding in which six bands of 8, 9, 12, 14, 18, and 21 kDa were added as the sperm matured through the cauda epididymis. These findings present new information on the changes in distribution of surface glycoproteins in baboon sperm during epididymal passage. There was some reorganization of the molecular structure of the sperm during epididymal maturation.

Animals↗