International journal of andrology最新文献

This issue of the International Journal of Andrology (IJA) is the last one. The reason for its disappearance is quite unprecedented: the two top journals in the field of andrology, IJA and its American counterpart, Journal of Andrology (JA) have decided to join forces rather than continue competing against each other. This historical move will undoubtedly strengthen the combined journal and the transatlantic collaboration between the two societies endorsing the two journals: the European Academy of Andrology (EAA) and the American Society of Andrology (ASA).

In this editorial, written jointly by the founder and long-term chairman of the IJA publication committee, and the current and former chief editors, we look back at the history of the journal and its achievements. A bit of bibliometric data are presented to reflect on the most discussed and cited topics during the journal’s existence. It is noteworthy that the current year, 2012, marks two anniversaries: 35 years of IJA and 20 years of EAA. Round anniversaries are a good excuse to look back but they are also a perfect opportunity for good wishes for the future.

The beginning of ‘organized andrology’ in Europe dates back to 1968 when I initiated the European Andrology Group, supported by Schering AG (Schirren & Toyosi, 1970). Independently, in 1970, a few clinicians and scientists interested in the development of andrology, from Barcelona, Spain, and Buenos Aires, Argentina, created the Comité Internaçional de Andrologia (CIDA), with Antoni Puigvert (Barcelona) and Roberto Mancini (Buenos Aires) elected as Presidents. The two groups learned about each other’s activities in 1970 when Mancini and I met at a Nobel Symposium on ‘Control of human fertility’ in Stockholm, Sweden. In 1972, CIDA arranged a meeting in Barcelona and I was elected as the next president. During CIDA’s initial years, financial support for its activities and congresses was provided by the Fundaçio Puigvert, run by an administrative board (Drs A. Aakvaag, W. Bardin, D. de Kretser, R. Eliasson and Miss M. Marti). Andrologia was used as the official journal but it served also as the official publication for the German Society of Andrology. After the First International Congress of Andrology organized in Barcelona (1975), CIDA decided to create its own journal and the first volume of IJA was published in 1978.

At the Second International Congress of Andrology in Tel Aviv (1981), CIDA was – as planned long before – transformed into the International Society of Andrology (ISA) with Eberhard (Ebo) Nieschlag as president. However, at that stage, it was not possible to transfer IJA to ISA as two of its member societies already had their own journals. Fundaçio Puigvert accepted to keep CIDA as a silent organization with the mission to continue publishing IJA. A publication committee was formed, with me as chairman. Financially

Progesterone is present in high concentrations (μm) in the vicinity of the cumulus-oophorous complex and considered a key signalling factor for human spermatozoa. Progesterone induces an instant increase in intracellular calcium concentration [Ca²⁺]_i despite the absence of the classical progesterone receptor in human spermatozoa. Progesterone causes changes in beating of the flagellum but can also induce acrosome reaction in human spermatozoa. Both these effects are mediated by increased intracellular Ca²⁺ but they are exerted at opposite ends of this highly polarized cell. A breakthrough came from two recent studies (Lishko et al., 2011; Strunker et al., 2011) which showed that progesterone causes activation of the Ca²⁺-permeable CatSper channel in human spermatozoa, suggesting that CatSper or an associated protein serves as the long sought binding site for progesterone in human spermatozoa.

Progesterone not only raises [Ca²⁺]_i in human spermatozoa, it also activates a complex series of signalling events and cell activities. In this issue of the International Journal of Andrology, Sagare-Patil et al. (2012) report that some of these progesterone-mediated effects have characteristics that suggest they are activated by mechanisms independent of CatSper. Sagare-Patil and colleagues used a classical approach to investigate the concentration and time-dependent effects of progesterone. They report clear differences in dose dependence between different responses to progesterone. Motility stimulation, hyperactivation, tyrosine kinase activity, ERK1/2 phosphorylation and P90RSK phosphorylation all showed dose-dependence over 0.01–1 μm, consistent with the action of progesterone on CatSper. Acrosome reaction, tyrosine phosphorylation (analysed from immunofluorescence), P38MAPK phosphorylation, JNK phosphorylation and AKT phosphorylation were dose-dependently induced over the range 1–10 μm progesterone, indicating involvement of a lower affinity binding site for progesterone. These findings are in line with a previous report that progesterone binding and Ca²⁺ mobilization in human spermatozoa occur at nm progesterone (consistent with CatSper), but that a second low-affinity phase requires ≥5 μm progesterone (Luconi et al., 1998).

CatSper is the only identified calcium-permeable channel that has been detected by patch clamp of human spermatozoa (Kirichok & Lishko, 2011). T-type channel blockers NNC 55–0396 (2 μm) and mibefradil (30 μm) abolish CatSper currents in patch clamped human spermatozoa (Lishko et al., 2011; Strunker et al., 2011). These compounds also significantly inhibited the progesterone-induced Ca²⁺ response, but the signal was not abolished (Strunker et al., 2011). Sagare-Patil et al. (

Calcium/calmodulin-dependent protein kinase IV (CAMK4) is a multifunctional serine/threonine protein kinase, which plays an important role in the spermatogenesis by phosphorylating protamines. It has been shown to be involved in the regulation of human sperm motility. Moreover, the Camk4 knockout mice were infertile because of severely reduced sperm count and morphological abnormalities. As no study is available on the association of this gene with male infertility, we analysed all the exons of CAMK4 gene in ethnically matched 283 infertile and 268 fertile Indian men. We identified twenty nucleotide substitutions, of which twelve were novel. Of these novel variants, eight were exclusively detected in infertile men. Moreover, two infertile men-specific mutations were non-synonymous replacing amino acids at the highly conserved region. In silico analysis predicted both of these mutations as ‘deleterious’. In addition to nucleotide substitutions, we identified five novel insertion–deletion mutations; of these, g.150264_66delGCG was exclusively found in two oligoasthenoteratozoospermic men. In silico analysis of infertile men exclusive mutations predicted that they can alter/diminish the potential binding sites of splicing factors, which may affect the mRNA splicing and protein translation. Our study suggests that the mutations in CAMK4 may lead to abnormal semen parameters.

Imbalance between the oestrogen and androgen levels in utero is hypothesized to influence testicular cancer (TC) risk. Thus, variation in genes involved in the action of sex hormones may contribute to variability of an individual’s susceptibility to TC. Mutations in testosterone pathway genes may alter the level of testosterone in vivo and hypothetically the risk of developing TC. Luteinizing hormone receptor (LHR), 5α-reductase II (SRD5A2) and androgen receptor (AR) are key elements in androgen action. A case-control study comprising 651 TC cases and 313 controls in a Norwegian population was conducted for investigation of polymorphisms in the LHR, SRD5A and AR genes and their possible association with TC. A statistical significant difference was observed in patients being heterozygous for the LHR Asn312Ser polymorphism when comparing genotypes between all TC cases and controls (OR = 0.66, 95% CI = 0.48–0.89, p_adj = 0.049). No statistically significant difference between the histological subtypes seminoma and non-seminoma was observed. Our results may suggest a possible association between genetic variation in the LHR gene and the risk of developing TC.

Premature ejaculation (PE) is one of the most prevalent male sexual dysfunctions. Selective resection of the dorsal nerve (SRDN) of penis has recently been used for the treatment of PE and has shown some efficacy. To further clarify the efficacy and safety of SRDN on PE, we performed a preliminary, randomized, placebo-controlled clinical observational study. Persons with the complaints of rapid ejaculation, asking for circumcision because of redundant foreskin, intravaginal ejaculation latency time (IELT) within 2 min, not responding to antidepressant medication or disliking oral medication were randomly enrolled in two groups. From April 2007 to August 2010, a total of 101 eligible persons were enrolled, 40 of them received SRDN which dorsal nerves of the penis were selectively resected, and those (n = 61) enrolled in the control group were circumcised only. IELT and the Brief Male Sexual Function Inventory (BMSFI) questionnaire were implemented pre- and post-operatively for the evaluation of the effect and safety of the surgery. There are no statistically significant differences in the baseline data including mean ages, mean IELTs, perceived control abilities and the BMSFI mean scores between the two groups. With regard to the post-operative data of the surgery, both IELTs and perceived control abilities were significantly increased after SRDN (1.1 ± 0.9 min vs. 3.8 ± 3.1 min for pre- and post-operative IELT, respectively, p < 0.01),whereas the post-operative results were not significantly improved for the control group (1.2 ± 0.7 min vs. 1.5 ± 1.1 min, p > 0.05). Also, there were no statistically significant differences both in BMSFI composite and subscale scores between the two groups after surgery. Hence, we conclude that SRDN is effective in delaying ejaculation and improving ejaculatory control, whereas erectile function is not affected. The results imply that SRDN may be an alternative method for the treatment of PE for some patients.

The effective separation of X- and Y-bearing chromosome spermatozoa has been a topic of major attraction to a number of scientific disciplines. Approaches have typically been based upon either the kinetic or the physical characteristics of spermatozoa. Much of the information available to date has either suggested conflicting evidence between different approaches or a lack of repeatability, while other robust and reproducible techniques require expensive equipment and are being questioned with relation to their safety in clinical applications. This study describes a safe and efficient method for the successful enrichment of the Y-bearing chromosome spermatozoa cells from their X counterparts in the human male using a simple approach based on centrifugation. Five donor candidates with normal semen profiles and proven fertility were recruited. In total, 20 semen specimens were processed using conventional swim-up. During each attempt, half of the swim-up product was subjected to the enrichment technique and the other half served as control. Parameters important for successfully skewing sex ratios included the relative centrifugal force, the duration of centrifugal separation and the number of centrifugation rounds. Assessment of samples following the separation technique was effected by a three-colour-labelled fluorescent in situ hybridization. More than 1000 spermatozoa for each donor specimen were assessed for the presence of an X or Y chromosome. The enrichment technique produced a significantly higher (p < 0.001) overall frequency of 85.5% for the Y-bearing chromosome spermatozoa in the experimental group (3606 X-bearing/21 209 Y-bearing) compared with a frequency of 50.1% in the control group (11 801 X-bearing/11 269 Y-bearing), where there was no statistically significant difference in the number of either X- or Y-chromosome-bearing spermatozoa. In conclusion, successful skewing of human Y-bearing chromosome spermatozoa can be reproducibly achieved by the use of simple swim-up followed by a meticulous centrifugation protocol.

The role of thyroid hormones in the control of erectile functioning has been only superficially investigated. The aim of the present study was to investigate the association between thyroid and erectile function in two different cohorts of subjects. The first one derives from the European Male Ageing Study (EMAS study), a multicentre survey performed on a sample of 3369 community-dwelling men aged 40–79 years (mean 60 ± 11 years). The second cohort is a consecutive series of 3203 heterosexual male patients (mean age 51.8 ± 13.0 years) attending our Andrology and Sexual Medicine Outpatient Clinic for sexual dysfunction at the University of Florence (UNIFI study). In the EMAS study all subjects were tested for thyroid-stimulating hormone (TSH) and free thyroxine (FT4). Similarly, TSH levels were checked in all patients in the UNIFI study, while FT4 only when TSH resulted outside the reference range. Overt primary hyperthyroidism (reduced TSH and elevated FT4, according to the reference range) was found in 0.3 and 0.2% of EMAS and UNIFI study respectively. In both study cohorts, suppressed TSH levels were associated with erectile dysfunction (ED). Overt hyperthyroidism was associated with an increased risk of severe erectile dysfunction (ED, hazard ratio = 14 and 16 in the EMAS and UNIFI study, respectively; both p < 0.05), after adjusting for confounding factors. These associations were confirmed in nested case-control analyses, comparing subjects with overt hyperthyroidism to age, BMI, smoking status and testosterone-matched controls. Conversely, no association between primary hypothyroidism and ED was observed. In conclusion, erectile function should be evaluated in all individuals with hyperthyroidism. Conversely, assessment of thyroid function cannot be recommended as routine practice in all ED patients.

Progesterone has been identified to be one of the physiological regulators of sperm hyperactivation and acrosome reaction. However, the high sensitivity of human spermatozoa to progesterone implies that many may undergo premature hyperactivation and acrosome reaction thereby compromising their ability to fertilize. We hypothesized that if a spermatozoon has to preclude the occurrence of these events prematurely, there should be differential dose- and time-dependent effects on motility and acrosome reaction. We observed that low concentrations of progesterone (10 and 100 nm) induce sperm motility and activate tyrosine kinase; higher concentrations (1–10 μm) are required to induce extracellular signal regulated kinases 1/2 (Erk1/2), p90 ribosomal S6 kinase (p90RSK), p38 mitogen-activated protein kinase (p38MAPK), c-Jun N-terminal kinase (JNK1) and AKT phosphorylation, hyperactivation and acrosome reaction. The induction of acrosome reaction and tyrosine phosphorylation in response to higher concentration of progesterone is not absolutely dependent on activation of T-type voltage-gated Ca²⁺ channel or CatSper as Mibefradil did not completely abrogate progesterone-mediated effects. These results imply that although the spermatozoa are sensitive to low concentrations of progesterone, they only activate motility and tyrosine kinase activation; higher concentrations are required to induce hyperactivation and acrosome reaction probably by activating multiple kinase pathways including the MAPK and AKT.

Haemorrhoids are associated with regional vascular abnormalities and rectal pain, which are hypothesized to increase the risk of erectile dysfunction (ED); however, few studies have investigated the association between ED and haemorrhoids. This case-control study aimed to estimate the association between haemorrhoids and ED by using a population-based data in Taiwan. We identified 6 310 patients with ED as cases and randomly selected 31 550 controls. Conditional logistic regression was performed to compute the odds ratio (OR) for having been previously diagnosed with haemorrhoids between cases and controls. The results show that haemorrhoids were found to be present among 1 572 (24.9%) cases and 4 491 (14.20%) controls. The OR for prior haemorrhoids among cases was 1.90 (95% CI = 1.78–2.03) when compared with controls after adjusting for monthly income, geographical location, hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity and alcohol abuse/alcohol dependence syndrome. Younger cases demonstrated a higher risk for prior haemorrhoids when compared with controls. In particular, the adjusted OR among cases <30 years old was 3.71 (95% CI = 2.74–5.02) when compared with controls. We concluded that there was an association between ED and a prior diagnosis of haemorrhoids.

Testosterone (T) and vitamin D (VD) interact in androgen deficient men, however, this interaction and subsequent semen quality and bone mineral density (BMD) status is not clear in infertile men. Our objective was to investigate T, VD, semen quality, BMD and their relationships in Chinese infertile men. We conducted a cross-sectional study of 559 men aged 20–40 years, including 195 fertile men, 9 infertile men with known risk factors for osteoporosis (WR) and 355 infertile men without known risk factors for osteoporosis (WOR). WOR infertile men constituted 314 oligo-, astheno-, teratospermic or normospermic infertile men (OATN men) and 41 non-obstructive azoospermic men (NOA men). Differences of parameters were assessed, and the relationships were adjusted by multiple linear regression. WOR infertile men had significantly lower T, lumbar spine and total hip BMD than fertile men (all p < 0.05). Bioavailable T (Bio-T) and 25-hydroxyvitamin D [25(OH)D] were independent determinants of BMD in WOR infertile men (all p < 0.01) but not in fertile men. After stratifying Bio-T, WOR infertile men had lower BMD than fertile men (all p < 0.05) in low Bio-T subgroups (Bio-T ≤ 11.6 nmol/L), but not high Bio-T subgroups (Bio-T > 11.6 nmol/L). 25(OH)D was an independent determinant of sperm motility and morphology in WOR OATN men (all p < 0.05), with only borderline significance in fertile men(motility: p = 0.047; morphology: p = 0.056). T determined sperm concentration (square root) and morphology in WOR OATN men (all p < 0.001). No correlations between T and 25(OH)D were found in all groups. We suggest that infertile men have lower T and BMD than fertile men. 25(OH)D and T were associated with low BMD and poor semen quality in infertile men.