International Journal of Andrology (INT J ANDROL )

Publisher: Comité Internacional de Andrologia; European Academy of Andrology, Blackwell Publishing


The Official Journal of the European Academy of Andrology. The International Journal of Andrology publishes papers on all aspects of andrology, ranging from basic molecular research to the results of clinical investigations. It also publishes full reviews and provocative editorials which discuss and review the hottest topics of the moment.The Journal's aims are simple - to promote and integrate basic and clinical research in andrology and to publish the latest ideas in the field.

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    International journal of andrology; Andrology
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Blackwell Publishing

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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Oxidative stress is implicated to play a vital role in the pathogenesis of various diabetic complications. While reproductive dysfunction is a well recognized consequence of diabetes mellitus, the underlying mechanisms are poorly understood. The present study aims to obtain insights into the incidence, extent and progression of oxidative impairments in testis and epididymal sperm (ES) in streptozotocin (STZ)-induced diabetic rat during early and progressive phase. Adult rats (CFT-Wistar strain) rendered diabetic by an acute dose of STZ (60 mg/kg bw, i.p.) were examined for induction of hyperglycaemia at 72 h, followed by the assessment of oxidative impairments in testis and ES over a 6-week period. Oxidative damage was ascertained by measuring the malondialdehyde levels, reactive oxygen species (ROS) generation, alterations in antioxidant defences and extent of protein oxidation. STZ induced a significant (2.5-fold) increase in blood glucose levels. In diabetic rats, both testis and ES showed enhanced status of lipid peroxidation measured as increased TBARS and ROS from week 2 onwards. These impairments in testis were consistent, progressive and accompanied by marked alterations in antioxidant defences and elevated protein carbonyls. Varying degree of reduction in the specific activities of antioxidant enzymes was evident in testis and ES, while the activity of glutathione-S-transferase (GST) was significantly elevated. Reduced glutathione (GSH) and vitamin E levels were consistently reduced in testis. Lipid dysmetabolism measured in terms of increased cholesterol, triglycerides and phospholipids was evident only beyond week 2 in diabetic testis. Taken together, these results indicate that the testis and ES are indeed subjected to significant oxidative stress in the STZ-diabetic rat both during early as well as progressive phase. It is hypothesized that oxidative impairments in testis which develop over time may at least in part contribute towards the development of testicular dysfunction eventually leading to testicular degeneration which culminates in reduced fertility during the progressive phase of STZ-induced diabetes in adult rats.
    International Journal of Andrology 01/2008; 30(6):508-18.
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    ABSTRACT: Cryopreservation imposes dramatic changes in boar sperm survivability but it is as yet unclear which part of the process affects the spermatozoa the most. The present study monitored, along the entire process of cryopreservation, the stability (PMS) of the architecture of the lipid plasma membrane and its integrity (PMI), as well as the kinetics of the processed spermatozoa using two portions from the boar ejaculate (P1 = the first 10 mL of the sperm-rich fraction, SRF; P2 = the rest of the ejaculate), frozen in a recently developed package, the MiniFlatPack (MFPs, 0.5 x 10(9) sperm/dose). Evaluation was made at four specific stages, viz. S1 = after collection (suspended in Beltsville thawing solution, BTS); S2 = at 15 degrees C (suspended in lactose-egg yolk, LEY); S3 = at 5 degrees C (suspended in LEY plus glycerol); and S4 = post-thaw. Both sperm kinetics (using computer-assisted sperm analysis, CASA) and PMS [i.e. the degree of lipid disorder and of the exteriorization of phosphatidylserine (PS) in the plasma membrane, measured by flow cytometry using Merocyanine-540 (M-540), and Annexin-V (AV) respectively], as well as plasma membrane integrity [PMI, i.e. the degree of membrane damage, measured using Yo-Pro-1 or propidium iodide (PI)] were assessed after incubation in BTS at 38 degrees C. Moreover, spermatozoa were challenged by incubation in modified Brackett-Oliphant medium (mBO+) with 37 mm of bicarbonate at 38 degrees C for 30 min, and their PMS and PMI further explored. Total sperm motility was significantly higher in P1 than in P2 along the entire process (S1-S4; p < 0.01), decreasing significantly at S4 for both fractions (p < 0.0001). The proportion of spermatozoa showing linear motility (LinM) was similar between ejaculate portions (P1 and P2), with a significant increase post-thaw (S4; p < 0.0001). During cooling (S1-S3) but not post-thaw (S4), lateral head displacement (LHD) differed between portions and changed along the stages (p < 0.01). Sperm velocity differed between portions in S1 (p < 0.01), but remained similar, independently of the portion, thereafter (S2-S4). Both PMS and the total number of live spermatozoa remained similar between S1 and S3 while incubated in BTS for both ejaculate portions. Sperm mortality increased post-thaw (S4) in both portions but the degree of lipid disorder remained low in the live cells (1.28% for P1; 1.55% for P2). Exposure to mBO+, on the other hand, significantly increased membrane lipid disorder along cooling (S1-S3; p < 0.0001), increasing the percentages of dead spermatozoa, especially post-thaw (around 70%, both portions). PS-exteriorization (AV) was not evident along the cryopreservation process in control (BTS) samples and exposure to mBO+ only induced minor variations. The data showed that kinetics, PMS and PMI of boar spermatozoa suspended in BTS (S1), LEY (S2) or LEY plus glycerol (S3) were maintained during controlled cooling but were altered by thawing, showing more characteristics of cell injury than of sperm capacitation. The spermatozoa were able to capacitate but the bicarbonate challenge destabilized the plasma membrane during initial cooling and accelerated membrane changes post-thaw. We conclude that capacitation of boar spermatozoa does not occur during controlled cooling.
    International Journal of Andrology 01/2008; 30(6):485-99.
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    ABSTRACT: The aetiology of varicocele is multifactorial although hormonal imbalance and oxidative stress play a key role in the progression of illness. No conclusive evidence has been presented previously, describing the changes in these two factors and the evolution of patients after varicocelectomy. Semen characteristics and hormonal profile were analysed in 36 infertile men with unilateral left varicocele and 33 age-paired controls (proved to be fertile men), after careful inclusion/exclusion selection criteria. Liposoluble and hydrosoluble antioxidants, oligoelements and enzyme activities of the antioxidant defence system were also determined in plasma and erythrocyte from antecubital and spermatic veins, and in spermatozoa. Data were compared between groups at different times before and after varicocelectomy. Decreased levels of liposoluble and hydrosoluble antioxidants and increased activities of the antioxidant defence system enzymes were observed in patients compared with controls. Varicocelectomy normalized this condition at different post-surgical times. Levels of Zn and Se in seminal plasma, protein carbonyls and fragmented DNA remained elevated up to 1 month after surgery. Luteinizing and follicle stimulating hormone concentrations exhibited a biphasic behaviour while testosterone was diminished in patients but normalized soon after varicocelectomy. The results clearly demonstrate the link between the antioxidant defence system, hormonal status and semen characteristics along the post-varicocelectomy period. We suggest that oxidative biomarkers may be appropriate in controlling the evolution of post-varicocelectomy patients, and antioxidant supplementation may improve the clinical condition of infertile men with varicocele.
    International Journal of Andrology 01/2008; 30(6):519-30.
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    ABSTRACT: The usefulness of treating varicocele in order to improve fertility is still a matter of debate. The aim of this study was to evaluate variations in seminal parameters and inhibin B concentrations in a group of males affected by varicocele and treated by percutaneous retrograde sclerotherapy in comparison with a group of patients who did not undergo varicocele treatment. Thirty-eight patients with left varicocele underwent spermatic vein phlebography and percutaneous retrograde sclerotherapy with hydroxy-polyaethoxy-dodecanol. Serum inhibin B, follicle-stimulating hormone (FSH), testosterone levels and seminal parameters (sperm concentration, motility and morphology) were performed before and 6 months after sclerotherapy. Forty patients with left varicocele who did not undergo sclerotherapy were studied as controls. A significant increase (p < 0.01) in serum inhibin B levels and a significant decrease (p < 0.05) in FSH levels were observed 6 months after treatment. Semen analysis showed a significant improvement in sperm concentration (p < 0.05) and progressive motility (p < 0.01) after treatment. In control group no significant variations in hormonal and seminal parameters were observed 6 months after the basal examination. Six months after the basal evaluation, inhibin B levels were significantly higher in treated subjects than in controls (p < 0.05) whereas FSH levels were significantly lower (p < 0.05). Sperm concentration and progressive motility were significantly increased (p < 0.05 and p < 0.001, respectively) in treated subjects in comparison with controls. In conclusion, varicocele sclerotherapy improves inhibin B levels and seminal parameters, confirming the positive effect of this treatment on spermatogenesis and Sertoli cell function.
    International Journal of Andrology 01/2008; 30(6):531-6.
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    ABSTRACT: Voice break is a late, but characteristic event in male puberty. Assessment of age at voice break may be a relevant marker for epidemiological studies of male pubertal development. We investigated the timing of voice break and its association with explanatory variables [calendar year of admission in the boys choir and pre-pubertal body mass index (BMI)] by survival analysis techniques based on retrospective analyses of age at voice break in 463 Danish choir boys who were studied over a 10-year period. We found an overall median age at voice break of 14.0 [13.9-14.6] years, and a statistically significant downwards trend in age at voice break in the 10-year period (1994-2003) (log-rank test p = 0.0146). There was a statistically significant difference in age at voice break between boys in the different BMI quartiles in pre-puberty (p = 0.00822) with a tendency towards early voice break with increasing BMI standard deviation scores. Thus boys in the heaviest quartile at 8 years of age had an increased risk of early voice break (RR of 1.74 [1.14-2.65]) approximately 6 years later, compared with boys in the thinnest quartile. The earlier voice break seen during the 10-year observation period could however not exclusively be explained by a general increase in BMI in that period. Our findings indicate that puberty, as assessed by age at voice break in boys, may be starting earlier in Denmark as it has been observed in the USA, and suggest a relationship between pre-pubertal BMI and the timing of puberty.
    International Journal of Andrology 01/2008; 30(6):537-42.
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    ABSTRACT: Low testosterone levels in men are associated with type 2 diabetes mellitus. Erectile dysfunction (ED) is a frequent complication of type 2 diabetes. The aim of our cross-sectional study was to investigate the relationship between ED and total, bioavailable and free testosterone levels in 198 men with type 2 diabetes. In addition, we examined the associations of various cardiovascular risk factors involved in the development of ED in type 2 diabetic men. We found that bioavailable and free testosterone levels were significantly lower in men with ED (p = 0.006 and 0.027 respectively) than those without ED. Sex hormone-binding globulin levels were also reduced, but there was no significant difference in total testosterone (TT) levels between men with and without ED. The severity of ED as assessed by International Index of Erectile Function scores was significantly associated with TT (r = 0.32; p < 0.001), bioavailable testosterone (r = 0.32; p < 0.001) and calculated free testosterone (r = 0.35; p < 0.001) levels. ED was more frequently observed in men with hypertension and a higher waist circumference (p = 0.03). There was also a higher prevalence of ED among smokers (p = 0.06), but there were no significant associations between ED and alcohol consumption or with BMI > 30. This study has shown that ED is associated with low bioavailable and free testosterone levels, age, visceral adiposity and hypertension in type 2 diabetic men.
    International Journal of Andrology 12/2007; 30(6):500-7.
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    ABSTRACT: Human semen spontaneously coagulates into a semisolid mass and then wholly liquefies in a process that may have some similarity to that of normal blood. This well described phenomenon is referred to as coagulation and liquefaction of semen. Besides other active components of the haemostatic system, semen contains a significant amount of functional tissue factor (TF). However, TF needs factor (F)VII in order to exert it actions. In this study, we assessed human semen for the presence of FVII and FVIIa, and related their levels to conventional fertility parameters. Using a functional, one stage, clotting assay based upon the prolongation of the prothrombin clotting time, using the ACL 300R analyser and an Imubind FVIIa ELISA assay, FVII and FVIIa levels were measured in 97 semen specimens obtained from sub-fertile (sperm counts <20 x 10(6)/mL), normally fertile (sperm counts >or=20 x 10(6) but <60 x 10(6)/mL), fertile sperm donors (sperm counts >or=60 x 10(6)/mL), vasectomized subjects and in a pooled normal semen parameters group (categorization into groups was based on the World Health Organization guidelines on fertility criteria). In addition, conventional semen parameters were analysed on all semen samples. Both FVII and FVIIa were quantifiable in human semen. The mean levels of FVII and FVIIa were 4.4 IU/dL and 12 ng/mL respectively. Despite the observed variations of FVIIa levels in the studied groups they did not meet statistical significance when the groups were tested against each other. However, seminal FVIIa levels showed a significant positive association with semen liquefaction time, sperm motility and semen volume. The anti-sperm antibodies and sperm-agglutination groups were also associated with raised seminal FVIIa levels. We observed no significant relationship between FVIIa levels and total sperm concentration, sperm count per mL (sperm density), sperm progression and days of sexual abstinence. This study demonstrates that human semen contains appreciable amounts of FVII and FVIIa. It is possible to quantify these using commercially available assays. There also appears to be a direct correlation between the levels of these factors and certain seminal parameters. This finding reinforces the concept of an active clotting system in human semen, by establishing the missing link in the activation of a TF-dependent pathway.
    International Journal of Andrology 12/2007; 30(6):543-9.
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    ABSTRACT: Adhesion between Sertoli cells and germ cells is important for spermatogenesis. Cadherins are Ca(2+)-dependent transmembrane proteins that mediate cell-cell adhesion. The aim of this study was to compare the expression of P-cadherin in unilaterally cryptorchid and busulphan-treated rat testes using immunohistochemistry. The pattern of expression of P-cadherin in the seminiferous epithelium changed with the stage of the seminiferous epithelium. The membranes of round spermatids and membranes and cytoplasm of spermatocytes were strongly positive. Our experiments revealed that busulphan treatment (2 doses - 10 mg/kg of body weight - 21 days apart) and cryptorchism led to destructive changes in the structure of seminiferous tubules, together with the decrease in P-cadherin expression. The expression of P-cadherin disappeared in the spermatids segregated from the epithelium while segregated spermatocytes remained still positive for P-cadherin during the 3- to 11-day cryptorchid period. In busulphan-treated animals, the expression of P-cadherin was dependent on the presence or absence of the spermatocytes and spermatids in the tubules. Strong positivity for P-cadherin was observed in the spermatocytes that re-appeared in the regenerating seminiferous epithelium. We suggest that P-cadherin participates in the architecture of adherens junctions in testis, plays an important role in maintaining normal spermatogenesis and that cryptorchism and busulphan treatment lead to adherens junction disintegration.
    International Journal of Andrology 11/2007; 30(5):430-8.
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    ABSTRACT: The comprehensive changes in testicular gene expression before and after haploid germ cell differentiation were examined using microarray analysis. Approximately 14,000 expressed sequence tag (EST) clones of Mouse FANTOM Array ver.1 were hybridized with probes generated from mRNA of adult and juvenile (17 days postpartum) testes before the onset of spermiogenesis. Of 1315 genes that exhibited reproducible changes in expression (p < 0.05), 46% exhibited an increase of twofold or more in adults compared to juveniles, and 22% a decrease of twofold or more. The analysis not only confirmed the reported haploid-specific expression of several known genes, but also provided new information on the differential expression of various other genes, including upregulated genes such as Allc and Skd3 and downregulated genes such as hbb b1, before or after the onset of spermiogenesis. Based on the fundamental difference in expression profiles, and molecular functions of the encoded products, the genes were classified into several groups: postmeiotically upregulated genes encoding various enzymes, structural and regulatory proteins, and chaperones, and downregulated genes encoding haemoglobins and oxidation/reduction-related proteins or the machinery associated with protein synthesis, such as ribosomal proteins.
    International Journal of Andrology 11/2007; 30(5):462-75.
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    ABSTRACT: Testosterone levels decrease with age. The mechanisms responsible for the age-related decrease in testosterone concentration are still being debated, and probably involve all three levels of the hypothalamo-pituitary-testicular axis. Luteinizing hormone (LH) concentration is often measured in combination with testosterone, but its value is questionable when considering the testosterone levels of older men. The objective of the present study was to examine the associations of endogenous gonadotropin and testosterone levels both in a cross-sectional cohort of 3447 men participating in the fifth Tromsø study and longitudinally in a cohort of 1352 men participating in both the fourth and the fifth Tromsø study. Total testosterone, LH, follicle-stimulating hormone and sex hormone-binding globulin levels were measured with immunoassay while free testosterone levels were calculated. Total testosterone and LH were independently and positively associated in the cross-sectional analyses (p < 0.001). In the longitudinal study, however, LH levels did not predict changes in total and free testosterone levels. Thus, in clinical practice, measuring gonadotropins seems to be of limited value in detecting hypogonadism in ageing men.
    International Journal of Andrology 11/2007; 30(5):445-51.
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    ABSTRACT: The in vitro effects of Candida albicans and its filtrates on the motility and ultrastructure of human spermatozoa from healthy donors were studied. A significant reduction in sperm progressive motility and signs of membrane alteration, directly related to contact time were observed. Distinct adhesion of spermatozoa to C. albicans and agglutination were observed. Light and transmission electron microscopy examinations showed that spermatozoa attached to C. albicans mainly via the head. Multiple ultrastructural lesions were present, which were the possible morphological reasons for spermatozoan immobilization observed in the present study. It is concluded that C. albicans as well as its filtrates had an inhibitory effect on human sperm motility and impaired the ultrastructure of human spermatozoa, which could be associated with male infertility.
    International Journal of Andrology 11/2007; 30(5):421-9.
  • International Journal of Andrology 11/2007; 30(5):484; author reply 484.
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    ABSTRACT: Leptin is active in both metabolism and reproduction. In fact, it seems to exert an inhibitory action on gonadal functions by reducing testosterone production. The presence of leptin in human and boar seminal plasma and in human spermatozoa has been demonstrated; recently, leptin receptors (Ob-R) have been localized in human spermatozoa, thus suggesting a possible action of this hormone even on these cells. Our aim was to verify whether leptin receptor [the long form (Ob-Rb)] is present in boar spermatozoa. Immunofluorescence and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques were employed. RNA was extracted from boar spermatozoa and a specific band (382 bp) for Ob-Rb was detected after RT-PCR. Ob-Rb was detected on acrosome, subequatorial area and either on the midpiece or on the whole tail. These localizations were maintained even in semen washed twice to eliminate seminal plasma. We conclude that Ob-R is present in boar spermatozoa where seminal plasma leptin can exert its effects.
    International Journal of Andrology 11/2007; 30(5):458-61.
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    ABSTRACT: Overexpression of the inhibitor of apoptosis protein (IAP) XIAP (BIRC4) and downregulation of its antagonist Smac/DIABLO (DIABLO) are associated with the onset and progression of various malignancies. In this study, real-time RT-PCR was used to quantify the mRNA expression of XIAP and Smac/DIABLO in normal testicular tissue (n = 19), testicular carcinoma in situ (CIS; n = 4), testicular seminomas (n = 64) and non-seminomatous germ cell tumours (NSGCT; n = 35). XIAP and Smac/DIABLO were commonly expressed in normal and malignant testicular tissue with no apparent differences in XIAP mRNA levels among the histologic subgroups. Smac/DIABLO levels, on the other hand, gradually decreased from normal testicular tissue to CIS and seminomas and finally to NSGCT (p < 0.001). An inverse trend was observed when calculating the XIAP-to-Smac/DIABLO ratio (p < 0.001). This ratio differed when comparing normal testicular tissue with CIS (p = 0.014), seminomas (p < 0.001) and NSGCT (p < 0.001) and when comparing seminomas with NSGCT (p = 0.002), whereas no such difference was observed between CIS and seminomas (p = 0.302). TGCT patients dichotomized by the overall median XIAP-to-Smac/DIABLO ratio were more likely to present with a high ratio in clinical stage (CS) III than in CS I or II (p = 0.034). These data indicate that the balance of mRNA expression between XIAP and Smac/DIABLO is altered in favour of antiapoptotic XIAP during the development and progression of TGCT. Thus the expression of proapoptotic Smac/DIABLO is lowest in NSGCT and stage III tumours.
    International Journal of Andrology 11/2007; 30(5):476-83.
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    ABSTRACT: We evaluated erectile haemodynamics in mice and characterized the corpus cavernosum morphologically. Four-month-old male BALB/c mice and Sprague-Dawley rats were used. The following stimulation parameters were tested to achieve maximal erectile responses: voltage, 1-6 V; frequency, 6-24 Hz; pulse width, 1 msec; duration, 1 min (n = 7 per group). In a separate group of mice and rats (n = 10 per group), we measured systemic arterial pressure by use of either a 24-gauge angiocatheter or smaller calibre PE-10 tubing. Cavernous tissues from mice, rats or patients with psychogenic erectile dysfunction were stained for factor VIII, alpha-actin and Masson trichrome. Electrical stimulation of the cavernous nerve in mice produced voltage-dependent erectile responses of up to 5 V, with the highest response at a frequency of 12 Hz. The maximal intracavernous pressure recorded at this stimulation parameter was comparable with that in rats. A PE-10 catheter was more reliable for measuring systemic arterial pressure in mice than was a 24-gauge angiocatheter, and the values recorded were similar between mice and rats. The content of endothelial cells, smooth muscle cells and collagen was similar between mice and rats. However, the cavernous tissue of both animals contained lesser amounts of smooth muscle cells and greater amounts of collagen than that of humans (p < 0.01). These results suggest that the mouse is a useful and technically feasible model for the study of penile erection and has functional and structural properties similar to those of rats.
    International Journal of Andrology 11/2007; 30(5):452-7.
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    ABSTRACT: The dogma of genome functionality has recently been challenged by identification of non-protein-encoding RNAs, including mi(cro)RNAs. These relatively small sequences interact with mRNA and in the mammalian system, are involved in fine-tuning the process of translation. miRNAs have been found to be of crucial importance for normal development, including stem cell formation. Recent interesting fundamental observations will be discussed in this paper, as well as their impact on the genesis of human germ cell tumours (GCTs), in particular those of the adult testis, seminomas and non-seminomas (type II), and spermatocytic seminomas (type III). miRNA cluster 371-373 is specifically involved in inhibition of cellular senescence induced by oncogenic stress in the type II GCTs. This explains the unusual presence of wild type P53, characteristic of this type of solid cancer. Specific sets of differentiating miRNA were found to characterize the various differentiation lineages within the GCTs, which simulate normal embryonic development.
    International Journal of Andrology 09/2007; 30(4):304-14; discussion 314-5.