International journal of andrology最新文献

Dear Editor,

Jorgensen et al. recently reported a trend towards lower sperm concentration from 1998 to 2006 among 18–19 year old army draftees from the Turku area in Finland (Jorgensen et al., 2011). This important observation indicates that semen quality may have been higher in the past. Most previous studies on secular trends have been based on samples coming from various populations that need not provide valid comparisons over time (Handelsman, 2001; Fisch, 2008).

Human semen quality is inferior comparing with other mammals (Sharpe, 1994; Joffe, 2010), and it is reasonable to speculate, that human sperm concentrations were higher in the past due to selective evolutionary forces (Czeizel & Rothman, 2002) although such effects may not cause major shifts in sperm counts across few decades (Slama & Leridon, 2002). If so, have modern avoidable exposures during recent decades impaired human spermatogenesis? The Finnish data came from the same population and although participation rates were low (<15%), these young men may not know enough about their fecundity to produce selection bias. Nevertheless, information on the participation rates within each time period is of interest to evaluate differential selection. The semen laboratory took part in a quality-control programme showing systematic bias, but probably not of a type that would generate a trend. Presenting deviations from the quality control standard at each time period would aid evaluation of a drift in laboratory results even though this is not expected.

The observed median sperm concentration among the young men was 60 mill/mL in 1998–99, 54 mill/mL in 2001–03 and 50 mill/mL in 2006, and the corresponding values adjusted for period of sexual abstinence and age were 67, 60 and 48 mill/mL. The difference between the latter was statistically significant. As transformation and adjustment almost doubled the range between highest and lowest median value, it is of interest to know what changed the estimates so much. Are results artefacts of the chosen statistical model? Thus, it would be of interest to compare the crude means, the unadjusted back-transformed means and adjusted back-transformed means to explore effects of transformation and adjustment separately. A model adjusted for some conventional potential confounders such as season, pre- and postnatal smoking and alcohol beverages and analyses of trends in serum concentrations of independent biological markers of spermatogenesis, as Inhibin B, would also be of interest. After all, the fluctuations in crude median sperm concentration values are not large, considering the huge variation of sperm concentration within and between men.

We kindly ask the authors to provide more information and some additional analyses because these data are important, and their interpretation has wide ranging implications. Furthermore, we encourage the authors to make their raw data available for others (Walport &

To assess the possible risk factors for developing pain in normospermic adult varicocoele patients, 42 adult patients with left painful varicocoele (group 1) and 35 age-matched patients with left painless varicocoele (group 2) were recruited to this study. All the patients had normal semen quality (spermatozoa density, motility and morphology). Pain score on a 10-cm visual analogue scale was used to assess the scrotal pain as a result of varicocoele. The severity of pain was defined as follows: mild pain (1–3 cm), moderate pain (4–6 cm) and severe pain (7–10 cm). The parameters for comparison included body mass index (BMI), the distance from the renal hilum to scrotum (DRS), semen quality and pH value, serum concentration of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, testosterone, alkaline phosphatase (Alk-p), lactate dehydrogenase (LDH), testicular volume and discrepancy (%), grade of varicocoele and peak retrograde flow (PRF) and spontaneous venous reflux (SVR) by colour Doppler ultrasound and scrotal temperature (ST). The mean ages were 27.8 and 27.1 years old in groups 1 and 2, respectively. By multivariate analysis, patients in group 1 had significantly higher PRF, ST, DRS and rate of SVR, and lower BMI than those in group 2. Furthermore, there were significant differences in PRF, DRS and BMI among patients in group 1 with different degrees of pain. Conclusively, normospermic adult patients with left painful varicocoele had significantly higher peak retrograde flow, ST, distance from the renal hilum to scrotum, and rate of spontaneous venous reflux and lower BMI than those with left painless varicocoele. Furthermore, varicocoele patients with severe pain had significantly higher peak retrograde flow and distance from the renal hilum to scrotum, and lower BMI than those with moderate and mild pain.

To assess the incidence and risk factors of cryptorchidism in Nice area. A 3-year prospective study was conducted at two maternity wards involving neonatal screening of boys born ≥34 weeks of amenorrhoea. Methodology was strict with examination at birth, 3 and 12 months by the same paediatrician. Two strictly matched controls were included for each case. Information on child and parents (medical history, pregnancy, lifestyle) was recorded using medical chart and self-administered questionnaires. A total of 102 of 6246 boys were born with cryptorchidism (prevalence 1.6%, 95 included). Half of them were still cryptorchid at three and 12 months with, however, 10% of secondary re-ascent (recurrent cryptorchidism) at 12 months, justifying long-term follow-up. Cryptorchidism at birth was associated with instrumental delivery, inguinal hernia and urogenital malformations, particularly micropenis and paternal history of cryptorchidism. Our results suggest that maternal exposure to anti-rust or phthalates could be a risk factor, whereas eating fruits daily seemed somewhat protective. Prevalence of cryptorchidism in our area is on the lower bracket compared with other countries, and is associated with both familial and environmental risk factors.

Nitric oxide (NO) is produced via oxidation of l-arginine by nitric oxide synthases (NOSs), and is known as inducible (iNOS), neuronal, endothelial or testis-specific. Suggesting important functions for NOS in the normal rat and mouse testis, iNOS is reported to be constitutively expressed in Leydig cells (LC), Sertoli cells (SC) and germ cells. In our study, we sought to provide further insights into the roles of iNOS in the adult mouse testis using iNOS^-/- mice. Perfusion-fixed testes from wild type (WT) and iNOS^-/- mice were used for histological and stereological evaluations. Some of the mice had been injected with ³H-thymidine to label proliferating cells and to determine the duration of spermatogenesis that was unaffected in iNOS^-/- mice. Both LC nuclear volume and individual cell size were significantly decreased in iNOS^-/- mice, but the total number of LC per testis was increased (p < 0.05) by approximately 16%. The number of SC per testis was strikingly increased (approximately twofold) in iNOS^-/- mice, and testis weight and DSP per gram of testis (spermatogenic efficiency) were similarly increased. The anogenital distance was also significantly increased in iNOS^-/- mice, and this key endpoint suggests that the augmentation observed for the SC number may be related to increased foetal T-exposure during the masculinization programming window. Compared with WT testes, the numbers of spermatocytes and spermatids and SC per tubule cross sections were significantly increased in iNOS^-/- mice. Except for stages V–VI and VII–VIII, iNOS^-/- mice exhibited approximately 3.5-fold fewer apoptotic germ cells than in WT mice. Taken together, our results provide new evidence that iNOS plays an important role in numerical and functional regulation of key somatic cells in the testis, which in turn impacts on germ cells and their survival and thus on daily sperm production.

Clinical left-over biosamples are an important source for medical research. Our aim is to ascertain the attitudes of andrology patients towards biosample donation. A survey of 866 andrology patients with diverse andrology conditions was conducted in Shanghai, China from May 2010 to December 2010. The response rate was 75.8%. Of the study patients, 61.4% (95% confidence interval, CI: 0.58–0.65) voiced the opinion that they were willing to donate the residual biosample; 32.0% refused to donate; and 6.6% stated that they were undecided. Unwillingness to give sample was independently associated with having a low level of education (p = 0.047, OR = 0.63, 95% CI: 0.39–0.995) and being infertile patients (p = 0.03, OR = 0.61, 95% CI: 0.39–0.95), while willingness was significantly associated with being cancer patients (p = 0.04, OR = 1.90, 95% CI: 1.03–3.50), being aged 18–29 years (p < 0.01, OR = 5.88, 95% CI: 2.85–12.16) and being aged 30–44 years (p = 0.01, OR = 2.17, 95% CI: 1.20–3.90). Most andrology patients would want to authorize every future research by themselves (82.4%) and obtain their individual research results (75.7%). Less than half of the willing respondents would want to donate semen (44.1%) and testis (41.3%). The results suggested that andrology patients’ willingness to donate samples was low, especially in case of infertile patients. More studies are required to elucidate further causes for the low willingness to donate sample among andrology patients.

The reproductive-derived serine protease inhibitor Kazal-type (Spink) has been identified in seminal plasma, and Spink–spermatozoa binding has been illustrated in many mammalian species including human. We used mice as experimental animal to study the mode of Spink action in the modulation of mammalian sperm activity. A Spink3-binding zone was cytochemically stained on the sperm head at apical hook separated from intact acrosome, whether the cells were capacitated or not. The Spink3–spermatozoa binding neither changed the population of cells in the uncapacitated, capacitated and acrosome-reacted status nor affected the capacitation-related protein phosphorylation and cell motility enhancement. Despite that, the Spink–spermatozoa interaction resulted in decreasing the intracellular calcium concentration ([Ca²⁺]_i) of the cell head and suppressing both the acrosome reaction induced by Ca⁺² ionophore A23187 and the cell fertility. Furthermore, Spink3 seen on the head of spermatozoa in the uterine cavity after coitus could be removed by the trypsin-like activity in the uterine fluid of oestrous females, and free Spink3 in the uterine cavity suppressed the protease activity. We integrated our data to shed light on the molecular mechanism of how Spink and its inhibiting protease are interplayed to modulate the activity of mammalian spermatozoa during their transit in the reproductive tract.

Male patients with an extra sex chromosome or autosome are expected to present primary hypogonadism at puberty owing to meiotic germ-cell failure. Scarce information is available on trisomy 21, a frequent autosomal aneuploidy. Our objective was to assess whether trisomy 21 presents with pubertal-onset, germ-cell specific, primary hypogonadism in males, or whether the hypogonadism is established earlier and affects other testicular cell populations. We assessed the functional status of the pituitary-testicular axis, especially Sertoli cell function, in 117 boys with trisomy 21 (ages: 2 months–20 year). To compare with an adequate control population, we established reference levels for serum anti-Müllerian hormone (AMH) in 421 normal males, from birth to adulthood, using a recently developed ultrasensitive assay. In trisomy 21, AMH was lower than normal, indicating Sertoli cell dysfunction, from early infancy, independently of the existence of cryptorchidism. The overall prevalence rate of AMH below the 3rd percentile was 64.3% in infants with trisomy 21. Follicle-stimulating hormone was elevated in patients <6 months and after pubertal onset. Testosterone was within the normal range, but luteinizing hormone was elevated in most patients <6 months and after pubertal onset, indicating a mild Leydig cell dysfunction. We conclude that in trisomy 21, primary hypogonadism involves a combined dysfunction of Sertoli and Leydig cells, which can be observed independently of cryptorchidism soon after birth, thus prompting the search for new hypotheses to explain the pathophysiology of gonadal dysfunction in autosomal trisomy.

Sertoli cells metabolize glucose, converting it to lactate that is used by developing germ cells for their energy metabolism. Androgens and oestrogens have metabolic roles that reach far beyond reproductive processes. So, the main purpose of this study was to examine the effect of sex steroid hormones on metabolite secretion/consumption in human Sertoli cells. Human Sertoli cell-enriched primary cultures were maintained in a defined medium for 50 h and glucose, pyruvate, lactate and alanine variations were determined using ¹H-NMR spectra analysis, in the absence or presence of 100 nm 17β-estradiol (E₂) or 100 nm 5α-dihydrotestosterone (DHT). The mRNA expression levels of glucose transporters, lactate dehydrogenase and monocarboxylate transporters were also determined using semi-quantitative RT-PCR. Cells cultured in the absence (control) or presence of E₂ consumed the same amounts of glucose at similar rates during the 50 h. During the first 15 h of treatment with DHT, glucose consumption and glucose consumption rate were significantly higher. Nevertheless, DHT-treated cells secreted a significantly lower amount of lactate than control and E₂-treated cells. Such a decrease was concomitant with a significant decrease in lactate dehydrogenase A mRNA levels after 50 h treatment in DHT-treated groups. Finally, alanine production was significantly increased in E₂-treated cells after 25 h treatment, which indicated a lower redox/higher oxidative state for the cells on those conditions. These results support the existence of a relationship between sex steroid hormones action and energy metabolism, providing the first assessment of androgens and oestrogens as metabolic modulators of human Sertoli cells.

Spermatogenesis requires progressive changes in gene expression mediated by hormonal and local factors. Regulated macromolecular movement between nuclear and cytoplasmic compartments enables these essential responses to changing extracellular cues, and dynamic production of the nucleocytoplasmic transporters and importin proteins, throughout gametogenesis in rodents implicates them as key mediators of germline differentiation. We examined normal adult human testis expression profiles of six importins plus five additional proteins involved in nucleocytoplasmic transport. Although most were detected in the nucleus during germline differentiation, importin α4 was exclusively observed in Sertoli and germ cell cytoplasm. Many proteins were present in round spermatid nuclei (importins α1, α3, β1, β3; exportin-1, Nup62, Ran, RanBP1, RCC1), and remarkable intense nuclear and/or nuclear-associated signals were detected for importin α1, importin α3 and Nup62 in spermatocytes. This study identifies conserved aspects of nucleocytoplasmic transport during spermatogenesis and extends our knowledge of the dynamic presence of these proteins, which indicates that they contribute to germ cell-specific cargo trafficking and potentially to other functions during human spermatogenesis. We also demonstrate for the first time that importin α3 is nuclear in spermatocytes, when exportin-1 is cytoplasmic, suggesting that nuclear transport is altered during meiosis.

Several recent studies have indicated that androgen disruption induced by the administration of anti-androgen flutamide during critical developmental stages results in various reproductive abnormalities, mainly in rodents. However, scarce data are available regarding the alterations caused by this toxicant on cell–cell adhesion molecules. Of note, there is no report on the expression and regulation of tight and adherens junction proteins in the boar. Therefore, the purpose of this study was to analyse whether foetal and neonatal exposure to flutamide affects the expression and distribution of ZO-1, occludin, β-catenin, and N-cadherin in testes of adult pigs. Moreover, to evaluate whether androgen signal was altered in the boar, testicular levels of testosterone and oestradiol and the expression of androgen receptor were examined. Flutamide (50 mg/kg bw) was injected into pregnant gilts during gestational days 20–28 and 80–88 (GD20, GD80), and into male piglets on postnatal days 2–10 (PD2). In the testes of all flutamide-exposed boars, expressions of ZO-1, N-cadherin and β-catenin were significantly decreased at mRNA and protein level, whereas expression of occludin was unchanged when compared with the controls. In addition, in severely damaged seminiferous tubules of PD2 pigs, mislocalization of ZO-1, N-cadherin and β-catenin was observed. Changes in junction protein expressions were accompanied by disturbed intratesticular androgen–oestrogen balance, although androgen receptor expression was not altered. Taken together, these results demonstrate that blockade of androgen action by flutamide during both gestational and neonatal periods affects the expression of ZO-1, N-cadherin and β-catenin in adult pig testes. Of concern, neonatal window seems to be most critical for the organization of BTB and consequently for normal spermatogenesis in the boar. It is likely that altered expression of junction proteins is related to insufficient testosterone production and/or excessive oestradiol synthesis, which may result from impaired Leydig cell function.