International journal of andrology最新文献

Recently, we reported an increased prevalence of chronic bacterial prostatitis (CBP) in patients with prostatitis syndromes (PS) and irritable bowel syndrome (IBS) compared with patients with PS alone. The aim of this study was to evaluate the frequency of male accessory gland infections (MAGI) in patients with CBP plus IBS and to compare the sperm parameters of patients with or without MAGI. Fifty consecutive patients with the following criteria were enrolled: (i) infertility; (ii) diagnosis of CBP; and (iii) diagnosis of IBS according to the Rome III criteria. The following two aged-matched control groups were also studied: infertile patients with CBP alone (n = 56) and fertile men (n = 30) who fathered a child within the previous 3 months. Patients and controls underwent to an accurate anamnesis, administration of the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) and the Rome III questionnaires for prostatitis and IBS, respectively, physical examination, and semen analysis. A significantly higher frequency of MAGI was found in patients with CBP plus IBS (82.0%) compared with the patients with CBP alone (53.6%) or the fertile men (0%). The presence of MAGI in the patients with CBP plus IBS was associated with a significantly lower sperm concentration, total number, and forward motility, and with a higher seminal leucocyte concentration compared with the patients with CBP alone and MAGI. Sperm normal morphology was similar in the groups of patients. All sperm parameters did not differ significantly in both the groups of patients without MAGI. The patients with CBP plus IBS had a significantly higher frequency of MAGI compared with the patients with CBP alone. This was associated with worse sperm parameters and, hence, poorer reproductive prognosis. We suggest to search for the presence of IBS in the patients with PS and in particular when CBP and/or worse sperm parameters are present.

Protein ubiquitination is a stable, covalent post-translational modification that alters protein activity and/or targets proteins for proteolysis by the 26S proteasome. The E1-type ubiquitin-activating enzyme (UBA1) is responsible for ubiquitin activation, the initial step of ubiquitin–protein ligation. Proteasomal proteolysis of ubiquitinated spermatozoa and oocyte proteins occurs during mammalian fertilization, particularly at the site of sperm acrosome contact with oocyte zona pellucida. However, it is not clear whether the substrates are solely proteins ubiquitinated during gametogenesis or if de novo ubiquitination also occurs during fertilization supported by ubiquitin-activating and -conjugating enzymes present in the sperm acrosome. Along this line of inquiry, UBA1 was detected in boar sperm-acrosomal extracts by Western blotting (WB). Immunofluorescence revealed accumulation of UBA1 in the nuclei of spermatogonia, spermatocytes and spermatids, and in the acrosomal caps of round and elongating spermatids. Thiol ester assays utilizing biotinylated ubiquitin and isolated sperm acrosomes confirmed the enzymatic activity of the resident UBA1. A specific UBA1 inhibitor, PYR-41, altered the remodelling of the outer acrosomal membrane (OAM) during sperm capacitation, monitored using flow cytometry of fluorescein isothiocyanate-conjugated peanut agglutinin (FITC-PNA). Although viable and motile, the spermatozoa capacitated in the presence of PYR-41, showed significantly reduced fertilization rates during in vitro fertilization (IVF; p < 0.05). Similarly, the fertilization rate was lowered by the addition of PYR-41 directly into fertilization medium during IVF. In WB, high Mr bands, suggestive of protein ubiquitination, were detected in non-capacitated spermatozoa by antibodies against ubiquitin; WB with anti-phosphotyrosine antibodies and antibodies against acrosomal proteins SPINK2 (acrosin inhibitor) and AQN1 (spermadhesin) revealed that the capacitation-induced modification of those proteins was altered by PYR-41. In summary, it appears that de novo protein ubiquitination involving UBA1 contributes to sperm capacitation and acrosomal function during fertilization.

Although obvious effects of obesity on female reproduction and oocytes are emerging, the effects on male fertility and sperm quality are less clear with studies reporting conflicting results. We hypothesize that male obesity affects sperm function and physiology probably as a result of elevated oxidative stress in spermatozoa and therefore elevated levels of sperm DNA damage and loss of function. Six-week-old C57/Bl6 male mice (n = 36) were randomly allocated to two groups: group 1 (n = 18) received a control diet, whereas group 2 (n = 18) received a high-fat diet (HFD). At the completion of a 9-week period, mice were sacrificed and spermatozoa were obtained. Sperm motility, concentration, intracellular reactive oxygen species (ROS) production and sperm DNA damage were measured. The ability of the sperm to undergo capacitation, acrosome reaction, sperm binding and ability to fertilize an oocyte were also assessed. The percentage of motile spermatozoa was decreased in the HFD group compared with controls (36 ± 2% vs. 44 ± 4%; p < 0.05). Intracellular ROS was elevated (692 ± 83 vs. 409 ± 22 units; p < 0.01) in the HFD group compared with controls. Sperm DNA damage was also increased (1.64 ± 0.6% vs. 0.17 ± 0.06%; p < 0.05) in the HFD group compared with the control group. Furthermore, the percentage of non-capacitated sperm was significantly lower compared with controls (12.34% vs. 21.06%; p < 0.01). The number of sperm bound to each oocyte was significantly lower (41.14 ± 2.5 vs. 58.39 ± 2.4; p < 0.01) in the HFD group compared with that in controls and resulted in significantly lower fertilization rates (25.9% vs. 43.9%; p < 0.01). This report provides evidence that obesity may induce oxidative stress and sperm DNA damage as well as decreased fertilizing ability. This is important as DNA damage in the sperm as a result of oxidative stress has been linked to poor reproductive outcomes.

High levels of spermatozoa DNA damage hinder fertility in vivo but not in vitro. It is a source of worry that following in vitro fertilization (IVF) spermatozoa DNA damage, if not repaired by the oocyte, might have a negative impact on the offspring. The aim of this study was to assess if a high spermatozoa DNA Fragmentation Index (DFI) is associated with alterations in birthweight (BW) and/or gestational length in IVF children. One hundred and thirty-one singleton pregnancies established by standard IVF or intracytoplasmic sperm injection (ICSI) were included in the study. DFI was measured by sperm chromatin structure assay (SCSA) in semen samples used for fertilization. DFI was categorized as low and high, using 20, 30, 40 and 50% as cut-off levels. Birthweight, gestational age, as well as gestational age adjusted BW score were used in a linear regression model as end points For none of the tested birth characteristics, statistically significant differences between the groups with low and high DFI were seen regardless of whether 20, 30, 40 or 50% were used as cut-off levels, both when the IVF and ICSI data were merged or analysed separately. Spermatozoa DNA damage as assessed by SCSA is not associated with BW or gestational length in IVF and ICSI children.

Previous studies reported correlations of CAG repeat length with sex hormone serum concentrations and cardiometabolic risk factors, but were limited by small cross-sectional samples. We used data of 1859 men aged 20–79 years from the population-based Study of Health in Pomerania (SHIP) to investigate the direct and modulating effects of CAG repeat length on androgen action and cardiometabolic risk factors. We performed cross-sectional and longitudinal linear and Poisson regression models adjusted for age, smoking, physical activity, alcohol consumption and body mass index. The CAG repeat length was categorized into quartiles and low total testosterone (TT) defined according to the age-specific (by decades) 10th percentile, respectively. Age-adjusted cross-sectional linear regression models showed a positive association between CAG repeat length and serum testosterone concentrations [β coefficient for TT, 0.099 (p = 0.028) and for free T, 0.002 (p = 0.001), respectively]. After a 5.0 year median follow-up period, men with CAG repeat length in the lowest quartile had an increased risk of incident low TT concentrations [relative risk (RR), 2.31; 95% confidence interval (CI), 1.18–4.55]. We found no direct association between CAG repeat length and cardiometabolic risk factors in cross-sectional and longitudinal multivariable linear regression analyses; whereas men with longer CAG repeat length and low TT concentrations showed the highest risk of incident MetS (RR, 1.51; 95% CI, 1.05–2.16). CAG repeat length is a risk factor of incident low TT concentrations and a contributing factor of testosterone-related cardiometabolic effects. The added clinical value of a combined assessment of CAG repeat length and serum TT concentrations merits further investigation.

Mitochondria of spermatozoa are different from the corresponding organelles of somatic cells, in both their morphology and biochemistry. The biochemical differences are essentially related to the existence of specific enzyme isoforms, which are characterized by peculiar kinetic and regulatory properties. As mitochondrial energy metabolism is a key factor supporting several sperm functions, these organelles host critical metabolic pathways during germ cell development and fertilization. Furthermore, spermatozoa can use different substrates, and therefore activate different metabolic pathways, depending on the available substrates and the physico-chemical conditions in which they operate. This versatility is critical to ensure fertilization success. However, the most valuable aspect of mitochondria function in all types of cells is the production of chemical energy in the form of ATP which can be used, in the case of spermatozoa, for sustaining sperm motility. The latter, on the other hand, represents one of the major determinants of male fertility. Accordingly, the presence of structural and functional alterations in mitochondria from asthenozoospermic subjects confirms the important role played by these organelles in energy maintenance of sperm motility. The present study gives an overview of the current knowledge on the energy-producing metabolic pathways operating inside human sperm mitochondria and critically analyse the differences with respect to somatic mitochondria. Such a comparison has also been carried out between the functional characteristics of human sperm mitochondria and those of other mammalian species. A deeper understanding of mitochondrial energy metabolism could open up new avenues of investigation in bioenergetics of human sperm mitochondria, both in physiological and pathological conditions.

Dear Editor,

Recently, a paper was published in this journal suggesting that prenatal exposure to phthalate may be associated with a less typical male-typical play behaviour in boys (Swan et al., 2010). Phthalates are used in a large variety of household products and abound in our environment. They are endocrine disruptors, i.e. they interfere with the reproductive endocrine system and possibly with prenatal personality development and are positively associated with symptoms of Attention deficit hyperactivity disorder (ADHD) in children (Kim et al., 2009). Air-born phthalates indoors at the time of conception were related to an increased risk for autism spectrum disorder (ASD) in the offspring (Larsson et al., 2009). The comorbidity between these two disorders is striking and in childhood sometimes difficult to distinguish. People with ASD seldom become parents; nevertheless, genetic factors are considered crucial for the aetiology of ASD. An increase of de novo mutations has been reported, associated with environmental mutagenic factors. Altogether there has been increasing interest in vulnerability to environmental factors.

Individuals with ASD have difficulty with imitation, social imagination, non-verbal communication, social reciprocity and mind reading. One hypothesis that has been advanced to account for the cognitive style in ASD, is referred to as ‘the extreme male brain’. Based on the fact that normal males tend to rely more on systemising than empathizing on psychometric tasks, whereas the opposite is shown in females, autism can be considered as an extreme of the normal male profile. This model views ASD as resulting from increased testosterone exposure in utero. However, males with ASD are not super-masculine physically, rather they often look young, have sparse body hair and a high-pitched voice. Many are androgynous, not only in appearance, but also in their self-concept and ambiguous in sexual preferences (Hellemans et al., 2007). Females with ASD are likewise androgynous and have elevated testosterone levels (Geier & Geier, 2007). In persons with gender identity disorder (GID) the prevalence of ASD is 10-fold compared to the normal population (de Vries et al., 2010).

The spectrum of causes for the recent dramatic increase in reported rates of ASD are still hotly debated and various explanations have been proposed, ranging from elderly fathers to early vitamin D deficiency. We put forward the hypothesis that environmental chemicals of our own making may contribute to the increase and, consequently, that we already are forming a new human, more logical and non-manipulative, more concrete, more androgynous and sensitive, less sexual and social, for the good and for the bad.

Expression of testicular angiotensin II (AT2) receptors in Sprague–Dawley rats at various stages of development (1 and 5 days, 2, 3, 4 and 7 weeks postnatal) were studied by in vitro autoradiography and Northern blot analysis. The receptors were labelled with ¹²⁵I-[Sar¹, Ile⁸]AT2 and differentiated into two subtypes according to their susceptibility to AT1 (losartan, 5 μM) or AT2 (PD123319, 5 μM) antagonists. Total AT2 receptor binding in the testis was highest at 1 day of age (8.12 ± 0.35 fmol/mg protein, mean ± secEM, n = 8) and decreased gradually thereafter (5 days: 6.9 ± 0.41, 2 weeks: 2.85 ± 0.10, 3 weeks: 1.64 ± 0.19, 4 weeks: 0.76 ± 0.09, 6 weeks: 0.77 ± 0.09 fmol/mg protein, n = 8–11). AT2 receptor binding was strikingly abundant in 1-day-old rat testis (6.98 ± 0.34 fmol/mg protein), while considerably less AT1 receptor binding (1.46 ± 0.19 fmol/mg protein) was observed. The relative amounts of each subtype did not change for the first 3 weeks but the 4-week-old rat testis contained almost exclusively AT1 receptors (0.63 ± 0.05 fmol/mg protein). Northern blot analysis showed that mRNA expression of both AT1 and AT2 types decreased with age. Microscopic emulsion autoradiography was undertaken to clarify the localization of binding. At 10 days of age, both AT1 and AT2 receptors were present in the interstitial area, whereas seminiferous tubules contained mainly AT2 receptors. At 7 weeks of age, no significant binding was observed in the seminiferous tubule and the interstitial area contained AT1 receptors exclusively. These results demonstrate expression of AT2 receptors in the rapidly growing testis and suggest that change in the levels of AT2 receptor subtypes may be relevant to development and/or growth of the testis.

During the epididymal maturation, spermatozoa interact with different populations of epididymosomes and sequentially acquire some epididymosome-associated proteins critical to sperm functions. Although very few proteins associated with epididymosomes have been identified, the physiological importance of these vesicles in the sperm maturation remains unclear. To document these relevant issues, lipid and protein analysis of epididymosomes from caput and cauda epididymal fluids was determined. Lipid analysis revealed a particular composition of specific phospholipids in these vesicles; the levels of phosphatidyl-ethanolamine, phosphatidyl-inositol and phosphatidyl-choline being higher in caput epididymosomes. From the 555 and 438 proteins identified in caput- and cauda-derived epididymosomes, respectively, 231 proteins were identified in both types of epididymosome. Proteins exclusively identified in caput and cauda epididymosomes are mainly enzymes and transporter molecules. The presence of several glycan-modifying enzymes is the hallmark of the caput epididymosomes proteome. Among the common proteins in both types of epididymosome, a subset of Rab and SNARE proteins implicated in vesicle trafficking and membrane fusion were identified. Together, these data suggest that epididymosome-associated proteins are involved in various molecular functions suggesting that during the epididymal transit, spermatozoa interact with different populations of epididymosomes, which could modify the male gamete in a sequential manner.