Spermatogenesis in varicoceles after correction of the blood supply to the testis

By means of light microscopy methods in experiments performed in 60 white rats with modelled venous congestion in the left testis and in 113 men suffering from varicocele of the 2d-3d degree complicated with certain disorders of fertility, the effect of blood correction has been studied in the gonads by switching off the caudal (inferior) epigastric vein. The experimental correction of the blood stream in the testes, according to the data of quantitative estimations, contributes to spermatogenesis. Corresponding positive results, while studying spermograms, are obtained in patients suffering from varicocele complicated with infertility. Application of this operation is expedient when conservative therapy as varicocele is uneffective.     

Oxidative damage to proteins and decrease of antioxidant capacity in patients with varicocele

To examine oxidative damage to blood proteins in the spermatic vein and seminal plasma antioxidant capacity of patients with varicocele, 30 young male patients with varicocele (group 1), 25 young male patients with subclinical varicocele (group 2), and 15 normal young males without varicocele (group 3) were recruited in this study. Varicocele and subclinical varicocele were confirmed by physical examination and Doppler ultrasonography. Blood samples were drawn from peripheral and spermatic veins before varicocelectomy. Plasma protein carbonyls were measured by a spectrophotometric assay after reacting with 2,4-dinitrophenylhydrazine. Protein thiols and ascorbic acid of seminal plasma were measured by spectrophotometric methods. We found that plasma protein carbonyls in the spermatic veins were significantly higher than those of corresponding peripheral veins in all 30 patients in group 1 and 12 patients in group 2 receiving varicocelectomy. Protein carbonyls in the spermatic veins of patients with varicocele (3.72 +/- 0.56 nmole/mg protein) and patients with subclinical varicocele (3.50 +/- 0.30 nmole/mg protein) were found to be higher than those of the control (2.35 +/- 0.33 nmole/mg protein). Protein thiols were 0.97 +/- 0.96, 1.50 +/- 0.89, and 3.49 +/- 0.81 nmole/ml, and ascorbic acid levels were 1.87 +/- 0.42, 2.13 +/- 0.24, and 2.38 +/- 0.07 mg/dl, in seminal plasma of the patients in groups 1, 2, and 3, respectively. Seminal plasma protein thiols and ascorbic acid levels in group 1 were significantly lower than those in groups 2 and 3, respectively. These results indicate that oxidative stress in the patients with varicocele and subclinical varicocele was higher than that of the control. We suggest that plasma protein carbonyls, and protein thiols and ascorbic acid of seminal plasma are useful markers for the assessment of oxidative stress in patients with varicocele and subclinical varicocele.     

Human sperm physiology: estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) influence sperm metabolism and may be involved in the pathophysiology of varicocele-associated male infertility

The mechanisms by which varicocele affects fertility remain undetermined. Estrogens play a key role in the human male reproduction and human sperm expresses the estrogen receptors (ERs) and aromatase. In this study, by Western blotting we evidenced the ERs content concomitantly in healthy sperm and in oligoastenoteratozoospermic (OAT) samples without and with varicocele. In varicocele a strong reduction of the ERβ was observed, while the ERα was almost absent. Besides, transmission electron microscopy (TEM) confirmed the reduction of ERs expression in "varicocele" sperm, indicating that varicocele has a detrimental effect on sperm structure at molecular level. To further define the estrogen significance in male gamete and the pathophysiology of varicocele we investigated both the expression of ERα and ERβ in normal and pathologic sperm samples as well as we evaluated estradiol (E2) action on lipid and glucose sperm metabolism. Responses to E2 treatments on cholesterol efflux, protein tyrosine phosphorylations, motility, and acrosin activity in varicocele sperm were reduced or absent. The evaluation of the triglycerides content, lipase and acyl-CoA dehydrogenase activities, suggest that E2 exerts a lipolytic effect on human sperm metabolism. Concerning glucose metabolism, it appears that E2 induces G6PDH activity concomitantly to the insulin secretion. In "varicocele" sperm, the E2 did not induce energy expenditure. OAT sperm had E2-responsiveness but in a lesser extent with respect healthy sperm. This study discovered a novel role for E2/ERs in human sperm physiology, since they modulate sperm metabolism and new detrimental effects related to the pathophysiology of the varicocele condition.     

Inhibition of testicular testosterone biosynthesis following experimental varicocele in rats

In an attempt to determine whether defective testicular testosterone (T) biosynthesis may be associated with a varicocele, an experimental study was performed in adult rats whereby a unilateral left varicocele was surgically created. At 2, 4, 8, and 12 wk following the creation of the varicocele, intratesticular T as well as the activities of three (17 alpha-hydroxylase, 17,20-desmolase, and 17 beta-hydroxysteroid dehydrogenase) of the five enzymes in the delta 4 pathway of testicular T biosynthesis were measured. Intratesticular T (ng/g testis +/- SEM) in the left testis decreased significantly from 121 +/- 21 in the control group to 59 +/- 8 in the two-wk varicocele group (p less than 0.01), and remained significantly suppressed throughout the experimental period. The T concentrations in the right testis paralleled those in the left in both the control and varicocele animals. At 2 wk following the creation of the varicocele, the activity (nmol/min/testis +/- SEM) of the 17,20-desmolase enzyme decreased significantly, from 115 +/- 8 in the left testis of control rats to 87 +/- 6 in the left testis of the varicocele animals (p less than 0.025), and remained low throughout the 12 weeks of the study. The activity of the 17 alpha-hydroxylase enzyme was significantly decreased at the 8th and 12th weeks of the study, while the 17 beta-hydroxysteroid dehydrogenase activity did not show any significant change during the study period. The enzyme activities in the right testis paralleled those in the left testis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reversible meiotic abnormalities in azoospermic men with bilateral varicocele after microsurgical correction.

Because of a possible relationship between microenvironmental disturbances and meiotic abnormalities and of a straight relationship between lower-quality semen in patient carrying a varicocele and first meiotic non-disjunction, bilateral bipolar testicular biopsies are realized according the thermic differential gradient described in varicocele. Systematic meiotic studies of multiple testicular biopsies from 65 azoospermic men with bilateral varicocele were done in a multi-centric study on microsurgical correction of bilateral varicocele with microthermic intra-operative evaluation using minimally invasive thermal microsensors (Betatherm 10K3MCD2). In the present study abnormal temperature raising, histomorphometric abnormalities (spermatocyte arrest) and meiotic abnormalities (class IIC) are strongly correlated. In the ten patients submitted to another testicular biopsy procedure six months after surgery for TESE, normal thermal differential is registered and no meiotic abnormalities recurrences are found.     

超氧化物歧化酶和Bcl-2在实验性精索静脉曲张大鼠睾丸中的变化

目的:建立大鼠实验性精索静脉曲张(experimental varicocele EV)的模式,测量睾丸中超氧化物歧化酶(superoxide dismutaseSOD)活性和Bcl-2的表达。方法:将40只雄性青春期Wistar大鼠随机分为EV8周组和12周组(各12只)和相应的假手术对照组2组(各8只),通过部分结扎左肾静脉建立大鼠EV模型,分别于术后8周、12周处死动物,测左侧精索静脉直径,用比色法测SOD 活力,免疫组化法测Bcl-2的表达。结果:成功建立了EV型,与相应的对照组相比左侧精索静脉直径明显增大(P<0.01)。光学显微镜下观察睾丸组织,发现大鼠睾丸生精上皮退变,曲细精管萎缩,间质水肿和精子发育阻滞。EV组双侧睾丸的SOD活性显著低于相应的对照组(P<0.01),左侧睾丸比右侧睾丸更低,但无明显统计学意义(P>0.05)。EV组双侧睾丸间质细胞中Bcl-2的染色指数与相应的对照组相比均显著降低(P<0.01),左侧睾丸染色指数比右侧睾丸下降更明显(P<0.01),EV12周组与 EV8周组相比,EV12周组染色指数更低(P<0.05)。SOD活性与Bcl-2的染色指数在0.01水平有显著相...     

Températures et varicocèles

Varicocele is considered to be responsible for male infertility by several authors, while varicocele may also exist in fertile men. Hyperthermia or “raised” testicular temperature is one of the pathophysiological mechanisms proposed to explain impaired spermatogenesis when a varicocele is present in infertile men. The reported clinical data in humans and experimental results of surgically-induced varicocele in animals indicate the following findings. In most studies, mean testicular and scrotal temperatures are bilaterally increased in populations of men with unilateral left varicocele compared to control populations. Similar results are observed following surgical induction of experimental left varicocele in animals. In the case of bilateral varicocele, the increase in mean temperature is similar to that observed in unilateral varicocele. Data concerning the effects of varicocelectomy on testicular or scrotal temperatures are still inconclusive in humans because of the discordant results in the small number of studies dealing with this topic. However, experimental data indicate that varicocelectomy results in recovery of normal mean temperature in animals submitted to surgically-induced varicocele, but experimental animal models of varicocele have failed to provide any explanation for the increase in temperature. In conclusion, although there is a relationship between varicocele and testicular temperature, testicular temperature is not increased in every case of varicocele.     

Selenium,Copper and Zinc in Seminal Plasma of Men with Varicocele,Relationship with Seminal Parameters

Varicocele has been associated with decrease in seminal parameters. Selenium (Se), copper (Cu), and zinc (Zn) are trace elements essential for normal spermatogenesis of mammals and play a critical role as antioxidant defense system enzymes. Se, Cu, and Zn are associated with sperm quality in fertile and infertile men. However, there is little information about Se, Cu, and Zn concentrations in semen in patients with varicocele and its association with seminal parameters. The purpose of this study was to determine the concentrations of Se, Cu, and Zn in semen of patients with varicocele and the relationship with seminal parameters. Total Reflection X-Ray Fluorescence was used for the fist time in the seminal fluid analysis. The concentration of selenium in men with varicocele was smaller than the normozoospermic group, while no differences were observed for both concentrations of zinc and copper. A significant positive correlation between zinc and selenium concentration was observed. Selenium in seminal plasma correlates with a good spermatozoa concentrations, motility, and morphology. Additionally, a significant positive correlation was observed between zinc levels and sperm count. In conclusion, a decrease in selenium concentration was associated with detriment of seminal parameters. A study should be conducted to evaluate the benefits of both zinc and selenium supplementation to improve seminal parameters in patients with varicocele.     

Progesterone, 17-OH-progesterone, androstenedione and testosterone plasma levels in spermatic venous blood of normal men and varicocele patients

Progesterone (P), 17-OH-progesterone (17-OH-P), Androstenedione (delta 4) and testosterone (T) plasma levels were measured in spermatic venous blood of twenty-nine varicocele patients (V) and in twelve normal subjects (N). Our data reveal a significant decrease of the mean testosterone in the spermatic blood of varicocele patients with respect to normal controls: (N = 1708.7 +/- 223.8 (SEM) nmol/l, n = 10. V = 1190.9 +/- 101.1 (SEM) nmol/l, n = 29. P less than 0.03). An inverse correlation has been observed between the age of varicocele patients and 17-OH-P (n = 29. y = -33.38x + 1384.70, r = -0.59, P less than 0.01) and delta 4 values (n = 23, y = -1.62x + 85.65, r = -0.49, P less than 0.05). The 17-OH-P/delta 4 ratio appears significantly augmented in varicocele patients with respect to normal controls (n = 4.80 +/- 0.86 (SEM), n = 12. V = 9.65 +/- 1.21 (SEM), n = 23.0.02 greater than P greater than 0.01). This indicates a deficiency in varicocele patients of 17-20 lyase activity. The positive correlation between the P/17-OH-P ratio and age of varicocele patients (n = 28, y = 0.007 x -0.090, r = 0.45, P less than 0.03) suggests a progressive impairment of 17-alpha-hydroxylase in such patients as they grow relatively older. These data demonstrated that the reduced spermatic levels of testosterone in varicoceles are due to the enzymatic impairment of testosterone biosynthesis, concerning firstly 17-20 lyase activity and secondly 17-alpha-hydroxylase activity. The latter enzymatic impairment is age related as is seen from the significant increase of the P/17-OH-P ratio in older patients.     

Place de l’embolisation percutanée de la varicocèle dans le traitement de l’infertilité

Objectives

To describe percutaneous embolization of varicocele and to evaluate the effect on fertility disorders.

Materials and methods

One hundred nineteen patients, aged 11 to 48 years, underwent percutaneous embolization for varicocele indicated by a fertility disorder in 23% of cases. Correction of the varicocele and resolution of associated pain, improvement of testicular trophicity and the effect on fertility were studied and a review of the literature was performed.

Results

Percutaneous embolization was performed using neuroleptanalgesia on an outpatient basis. The technique combined venous sclerotherapy and placement of coils in the gonadal vein. The technique was successful in 95% of cases and one complication was observed. At 3 months, the varicocele and related pain had resolved in 98% of treated patients. According to previous reports in the literature, the relations between varicocele and fertility disorders are still unclear, but improvement of fertility (semen quality and conception rates) after varicocele repair has been established.

Conclusion

Although the consequences of varicocele on fertility have not been fully elucidated, treatment of varicocele appears to be beneficial. Percutaneous embolization of varicocele is a safe and effective alternative to surgery. This technique, based on a urological and radiological consensus, is the first-line treatment for varicocele in our institution.     

Decreased protein tyrosine phosphorylation and membrane fluidity in spermatozoa from infertile men with varicocele

Varicocele is a prevalent pathology among infertile men. The mechanisms linking this condition to infertility, however, are poorly understood. Our previous work showed a relationship between sperm functional quality and the ability of spermatozoa to respond to capacitating conditions with increased membrane fluidity and protein tyrosine phosphorylation. Given the reported association between varicocele, oxidative stress, and sperm dysfunction, we hypothesized that spermatozoa from infertile patients with varicocele might have a combined defect at the level of membrane fluidity and protein tyrosine phosphorylation. Semen samples from infertile patients with and without grade II/III left varicocele were evaluated for motion parameters (computer-assisted semen analysis [CASA]), hyperactivation (CASA), incidence and intensity of protein tyrosine phosphorylation (phosphotyrosine immunofluorescence and western blotting), and membrane fluidity (Laurdan fluorometry), before and after a capacitating incubation (6 hr at 37 degrees C in Ham's F10/BSA, 5% CO(2)). Spermatozoa from varicocele samples presented a decreased response to the capacitating challenge, showing significantly lower motility, hyperactivation, incidence and intensity of tyrosine phosphorylation, and membrane fluidity. The findings reported in this article indicate that the sperm dysfunction associated to infertile varicocele coexists with decreased sperm plasma membrane fluidity and tyrosine phosphorylation. These deficiencies represent potential new pathophysiological mechanisms underlying varicocele-related infertility.     

Varicocèle: physiopathologie et approches thérapeutiques

Varicocele is a frequent disease in infertile men (30–40%) and has a harmful effect on growth of the testis and spermatogenesis, which deteriorates with increasing length of exposure to varicocele. Clinical varicocele (grade 2 and 3), especially in younger patients, represents a logical indication for treatment of varicocele in infertile men. However, all causes of infertility (male and female factors) must be considered before treatment. The main factors of failure of spermatogenesis are: hormonal disturbances (hypothalamo-hypophysogonadal status) and testicular thermoregulation anomalies. They should be considered to be prognostic factors for treatment.     

Varicocele and Infertility in Men

Varicocele is an important cause of infertility in men. The exact mechanism by which varicocele depresses spermatogenesis is unknown but probably the retrograde flow of blood rich in catecholamines into the testes plays a major role.Because subfertile semen qualities are present in a large percentage of men with varicocele and because the response to surgical procedures is very good, high ligation of the left internal spermatic vein is recommended in men with varicocele and infertility.     

Current management of adolescent varicocele

The finding of varicocele in an adolescent male is common. Varicocele rarely causes symptoms and is often diagnosed on the routine physical examination. There is clear association between varicocele and male factor infertility; however, there is debate about whether, when, and whom to treat when present in adult or adolescent males. This review of the epidemiology, etiology, pathophysiology, and treatment of the adolescent with varicocele will provide the reader with tools to make appropriate decisions in dealing with this condition.     

New methods of X-ray surgical diagnosis and treatment of varicocele in children and adolescents

The authors studied 520 patients with left-sided varicocele by left-sided phleborenotesticulography of Doppler ultrasonography, tensiometry of the left renotesticular venous system, blood gas composition, hormonal parameters, and etc. They present rationale for and evidence illustrations of aortomesenteric compression of the left renal vein, left-sided phleborenal hypertension prior to and after surgery for endovascular occlusion of the left testicular vein, before and following intervenous proximal testiculoiliac venous bypass surgery. The data of andrological dysfunction in patients with varicosis of the pampiniform plexus and spermatic cord (varicocele) are presented. An algorithm of examination and treatment of this cohort of patients, by using both miniinvasive techniques (for X-ray endovascular occlusion of the temporal veins under local anesthesia) and high tech operations using microsurgical techniques (testiculoiliac venous anastomosis), is outlined.     

Color Doppler sonography of normal male genitalia and varicocele

The present paper reports on the results of complex sonographic examination of scrotum organs in 116 patients. The study was performed with Siemens sonographic unit. According to clinico-laboratory data and results of operative intervention, the patients were divided into two groups. The 1st group (8 persons) had no pathology in the scrotum organs, the 2nd group (98 patients) had diagnosis of varicocele. In norm capsular, centripetal and transmeridian arteries were visualized in the projection of testis in colour Doppler sonography. Resistancy index was measured. The group with varicocele in colour Doppler sonography with Valsalva test showed a prolonged retrograde wave of blood flow during the whole period of tension. To determine the stage of pathologic process, a scale system had been used. Doppler sonography enables to reveal various types of reflux. The character of reflux determines a pathogenetic cause of varicocele that effects on the choice of the method of operative intervention. Parameters of colour Doppler sonography allow to determine the stage of the disease and reveal subclinical varicocele in cases when pampiniform plexus is absent, but significant hemodynamic changes take place. The data of Doppler sonography have been confirmed by the results of operative intervention.     

Functional significance of the serum/saliva testosterone ratio in various diseases]

Serum/salivary testosterone ratio (ST/SlvT) expresses the relationship in absolute values between bound and unbound testosterone. This ST/SlvT ratio in supposedly healthy men (n = 25) and women (n = 72) and in patients with several disorders, prostatic carcinoma (n = 19), varicocele (n = 9) and hirsute women (n = 16), has been studied. Both serum and salivary testosterone were measured by an RIA method. ST/SlvT ratio values found in healthy men (78.4 +/- 30.9) did not differ significantly from values found in the varicocele group (111.1 +/- 49.3), but a significant difference (p less than 0.001) from those found in men with prostatic carcinoma (12.3 +/- 7.2) was observed. When the ST/SlvT ratio values obtained in healthy women (18.1 +/- 7.3) were compared with those obtained in hirsute women (1.56 +/- 5.7) no significant differences were observed. The results obtained may indicate the dissociation among the hormone transport, testosterone metabolic clearance and hormone secretion by the salivary glands.     

Apport de l’embolisation de la varicocèle chez 51 patients infertiles

This study evaluated the changes induced on the parameters of the sperm count four months after sclero-embolization of varicocele. From February 1993 to February 2000, 51 infertile patients with testicular hypotrophy or oligospermia were treated by percutaneous sclero-embolization of varicocele. All patients underwent preoperative diagnostic evaluation by semen analysis, Doppler flowmetry or color Doppler ultrasound and venography. Scrotal ultrasound was performed to evaluate the echogenicity of the testes, their volume and funicular vein enlargement during Valsalva manoeuvre. Patients were reviewed four months after sclero-embolization with semen analysis. Clinical follow-up showed complete resolution of the varicocele in 94% of cases (47 patients), while the varicocele persisted in two cases. In 2% of cases (1 patient), selective catheterization of the internal spermatic vein was impossible. Four months later, analysis of semen parameters showed an increased number of spermatozoa. In 69.4% of oligospermic cases, the sperm count was at least tripled. The time-course of the sperm count (average) was as follows: in a total of 50 patients with pre- and post-embolization evaluation, sperm count increased from 19.6 106/ml to 26.7 106/ml. In the population of 36 patients with a sperm count <20 106/ml (i.e. with oligospermia or azoospermia), the sperm count increased from 3 106/ml to 14.6 106/ml. In the subgroup of patients with oligospermia (1–20.106/ml), the sperm count increased (p<0.01) from 5.32 106/ml to 22.32 106/ml; in the subgroup of patients with severe oligospermia (0–1 106/ml), the sperm count increased (p<0.01) from 0.188 106/ml to 3.5 106/ml. Semen analysis was improved in 1 of the 4 patients with azoospermia. In conclusion, sclero-embolization improved sperm count in this population of infertile patients with varicocele and testicular hypotrophy. In vitro fertilization or intra-uterine insemination can therefore be considered in the place of ICSI.     

ELV对青春期大鼠睾丸中VEGF与VEGFR2蛋白表达的影响

目的研究血管内皮生长因子(VEGF)及其受体2(VEGFR2)在实验性左侧精索静脉曲张大鼠睾丸中的表达和定位,探讨精索静脉曲张中VEGF和VEGFR2的可能作用。方法通过部分结扎左肾静脉建立大鼠实验性左侧精索静脉曲张模型,于术后2周和4周取材,采用免疫组化法检测VEGF、VEGFR2在睾丸上的表达变化。结果 ELV2周与4周组大鼠两侧睾丸中VEGF蛋白表达均上调,但ELV组间VEGF蛋白表达没有明显变化;ELV2周组大鼠睾丸中VEGFR2蛋白的表达与对照组比较增强,而4周组比对照组和2周组均显著增强。结论实验性左侧精索静脉曲张对VEGF、VEGFR2蛋白的表达有影响,说明它们与男性不育可能有一定的关系。     

Venography in the evaluation of the results of surgical treatment of varicocele in children]

The paper is concerned with analysis of the results of intraoperative phlebotesticulography, performed in 50 patients with varicocele of degree I-II during Ivanissevich's operation. The effect of surgical intervention was shown to depend upon the quality of ligation of the testicular vein, some parts of which are anastomosed between themselves. The localization of this anastomosis is revealed by means of intraoperative phlebotesticulography, which permits increasing the results of surgical treatment and predicting a course of a postoperative period.