Obesogens are chemicals that directly or indirectly lead to increased fat accumulation and obesity. Obesogens have the potential to disrupt multiple metabolic signalling pathways in the developing organism that can result in permanent changes in adult physiology. Prenatal or perinatal exposure to obesogenic endocrine disrupting chemicals has been shown to predispose an organism to store more fat from the beginning of its life. For example, excess oestrogen or cortisol exposure in the womb or during early life resulted in an increased susceptibility to obesity and metabolic syndrome later in life. This review focuses on the effects of environmental chemicals, such as the model obesogen, tributyltin (TBT), on the development of obesity. We discuss evidence linking the obesogenic effects of TBT with its ability to activate the peroxisome proliferator-activated receptor gamma and stimulate adipogenesis. We also discuss how TBT and other environmental obesogens may lead to epigenetic changes that predispose exposed individuals to subsequent weight gain and obesity. This suggests that humans, who have been exposed to obesogenic chemicals during sensitive windows of development, might be pre-programmed to store increased amounts of fat, resulting in a lifelong struggle to maintain a healthy weight and exacerbating the deleterious effects of poor diet and inadequate exercise.
The accumulating effects of exposure to electromagnetic radiation emitted by a conventional mobile phone (standby position) on the testicular function and structure are not yet fully investigated. To study these effects longitudinally, a total of 24 adult male rabbits were randomly and equally divided into three groups. Rabbits in the first (phone) group were exposed, in specially designed cages, to radio frequency emitted from the mobile phone (800 MHz) in a standby position opposite to that of testes for 8 h daily for 12 weeks. The second group consisted of the stress controls which were kept in the same kind of cages to appreciate any cage-induced anxiety. The third group included the ordinary controls which were kept in the conventional roomy cages. Semen analysis and sperm function tests (viability, hypo-osmotic swelling and acridine orange) were conducted weekly. Histological testicular sections and serum total testosterone were also evaluated. A drop in the sperm concentration appeared in the phone group at week 6. This became statistically significant at week 8, compared with the two control (stress and ordinary) groups (133, 339 and 356 × 106/mL, respectively) and to the initial sperm count (341 × 106/mL) of this group. Motile sperm population showed similarity amongst the three study groups until week 10 when it declined significantly, and thereafter in the phone and stress control groups, with more significant decline in the phone animals (50, 61 and 72.4%, respectively). Histological examination showed also a significant decrease in the diameter of seminiferous tubules in the phone group vs. the stress and ordinary controls (191 μm vs. 206 and 226 μm, respectively). The other study points did not show any difference. In conclusion, low intensity pulsed radio frequency emitted by a conventional mobile phone kept in the standby position could affect the testicular function and structure in the adult rabbit.
Extracorporeal shock wave therapy improves erectile function in patients with Peyronie's disease. However, erectile dysfunction still persists in many cases. We aimed to investigate the effects of extracorporeal shock wave therapy plus tadalafil 5 mg once daily in the management of patients with Peyronie's disease and erectile dysfunction not previously treated. One hundred patients were enrolled in a prospective, randomized, controlled study. Patients were randomly allocated to receive either extracorporeal shock wave therapy alone for 4 weeks (n = 50) or extracorporeal shock wave therapy plus tadalafil 5 mg once daily for 4 weeks (n = 50). Main outcome measures were: erectile function (evaluated through the shortened version of the International Index of Erectile Function), pain during erection (evaluated through a Visual Analog Scale), plaque size, penile curvature and quality of life (evaluated through an internal questionnaire). Follow-up evaluations were performed after 12 and 24 weeks. In both groups, at 12 weeks follow-up, mean Visual Analog Scale score, mean International Index of Erectile Function score and mean quality of life score ameliorated significantly while mean plaque size and mean curvature degree were unchanged. Intergroup analysis revealed a significantly higher mean International Index of Erectile Function score and quality of life score in patients receiving the combination. After 24 weeks, intergroup analysis revealed a significantly higher mean International Index of Erectile Function score and mean quality of life score in patients that received extracorporeal shock wave therapy plus tadalafil. In conclusion extracorporeal shock wave therapy plus tadalafil 5 mg once daily may represent a valid conservative strategy for the management of patients with Peyronie's disease and erectile dysfunction.
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 pathogenesis of recurrent spontaneous abortion (RSA) is multi-factorial, complex and poorly understood. In the present study, semen parameters, including sperm chromatin integrity, sperm concentration, sperm motility and sperm morphology, were compared between 111 men whose partners had a history of unexplained RSA (RSA group) and 30 healthy fertile men (control group). The RSA group was further separated into three subgroups, depending on their reproductive outcome during the 12 months after they were enrolled in the study: the pregnancy subgroup consisted of 43 men whose partners achieved a successful pregnancy up to at least the 24th week of gestation; the abortion subgroup included 31 men whose partners experienced further abortions; and the infertile subgroup had 37 men whose partners did not have any positive pregnancy test after regular, unprotected intercourse. Significantly lower proportion of sperm with normal morphology was found in the abortion subgroup (14.7 ± 4.3%) than in the control group (17.5 ± 5.0%). Sperm concentrations were significantly lower in the infertile subgroup (55.7 ± 24.1%) than in the controls (68.6 ± 27.8%). The rates of abnormal sperm chromatin integrity were significantly higher in the abortion (16.7 ± 7.7%) and infertile (16.3 ± 6.6%) subgroups, compared to the control group (13.0 ± 4.4%). Logistic regression analysis showed that the subsequent reproductive outcome of the 111 RSA patients was negatively correlated to the rates of abnormal sperm chromatin integrity. In conclusion, sperm chromatin integrity, sperm morphology, and sperm concentration were associated with future reproductive outcome of RSA patients. The sperm chromatin integrity was a significant predictor for future abortion and infertility.
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.
It has been demonstrated that intracavernous injection of bone marrow-derived mesenchymal stem cells (BM-MSCs) had beneficial effects on improving erectile function in type-1 diabetic rats. This study was designed to investigate the neurotrophic effect of BM-MSCs for type-1 diabetic rats. Streptozocin-induced type-1 diabetic rats were randomly divided into three groups: diabetic group, BM-MSCs-treated group and BM-MSCs-conditioned medium-treated group. At the 3d, 1 and 2w time points after BM-MSCs injection, three randomly selected rats in MSCs group were sacrificed and penile samples were harvested to detect BM-MSCs in penile tissue. Four weeks after intracavernous injection of BM-MSCs or BM-MSCs-conditioned medium, intracavernous pressure (ICP) was assessed to evaluate the erectile function. Immunohistochemistry was used to track labelled BM-MSCs in penile tissue and to detect neuronal nitric oxide synthase (nNOS) and neurofilament (NF) positive fibres in penile dorsal nerve. Enzyme lined immunosorbent assay (ELISA) was used to measure the concentrations of vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in BM-MSCs-conditioned medium. BM- MSCs secreted detectable levels of VEGF, BDNF and NGF. Intracavernous injection of BM-MSCs improved erectile function in diabetic rats. The functional improvement was accompanied by promoted nNOS and NF positive nerve fibres within penile dorsal nerve in type-1 diabetic rats. Histological data revealed a time-dependent decrease in the number of BM-MSCs in the corpus cavernosum following injection. Furthermore, the beneficial effect of BM-MSCs was partially repeated by BM-MSCs-conditioned medium. Intracavernous injection of BM-MSCs is effective in improving nerve regeneration in diabetic rats. Paracrine effects of BM-MSCs are probably involved in the improvement.
Chromosomal polymorphism has been reported to be associated with infertility, but its effect on IVF/ICSI-ET outcome is still controversial. To evaluate whether or not chromosomal polymorphism in men plays a role in spermatogenesis and the outcome of IVF/ICSI-ET, we retrospectively analysed 281 infertile couples. Measures included fertilization rate, implantation rate, pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate, early miscarriage rate and preterm rate. Men with chromosomal polymorphism had significantly higher frequencies of severe oligozoospermia and azoospermia than those without (37.12% vs. 16.11%, p < 0.001; 27.27% vs. 10.74%, p < 0.001; respectively). Significantly, lower fertilization rate (68.02% vs. 78.00%, p < 0.001) and clinical pregnancy rate (45.00% vs. 66.67%, p = 0.031) were observed in polymorphism-carrying men with severe oligozoospermia compared with non-carriers with severe oligozoospermia. This suggests that chromosomal polymorphism has adverse effects on spermatogenesis, negatively influencing the outcome of IVF/ICSI-ET treatment. Polymorphic variations on the Y chromosome have been found to be the most prevalent polymorphism in infertile men, most frequently occurring in patients with severe oligozoospermia.
The purpose of this study is to investigate the possible underlying pathogenesis of erectile dysfunction(ED) in young men with low risk of coronary heart disease and no well-known aetiology. To conduct this study, 122 patients with ED under the age of 40 were enrolled, along with 33 age-matched normal control subjects. The patients with ED had significantly higher levels of systolic blood pressure (SBP), total cholesterol and triglyceride, high sensitivity C-reactive protein (hs-CRP), greater carotid intima-media thickness (CIMT) and Framingham risk score (FRS) than the control group, though all of these values were within the respective normal range. Further, the brachial artery flow- mediated vasodilation (FMD) values were significantly lower in ED patients and correlated positively with the severity of ED (r = 0.714, p < 0.001). When these significant factors were studied in the multivariate logistic regression model, FMD, SBP, hs-CRP and FRS remained the statistical significance. The receiver-operating characteristic (ROC) analysis demonstrated that FMD had a high ability to predict ED in young male with low FRS [area under the curve (AUC) 0.921, p < 0.001]. The cutoff value of FMD <10.25% had sensitivity of 82.8% and specificity of 100% for diagnosis of ED. FRS and hs- CRP were also proven to be predictors of ED (AUC 0.812, p < 0.001; AUC 0.645, p = 0.011, respectively). The results of this study validated that subclinical endothelial dysfunction and low-grade inflammation may be the underlying pathogenesis of ED with no well-known aetiology. Young patients complaining of ED should be screened for cardiovascular risk factors and possible subclinical atherosclerosis. Measurement of FMD, hs-CRP and FRS can improve our ability to predict and treat ED, as well as subclinical cardiovascular disease early for young male.
Various epidemiological studies in relatively large cohorts of patients with Klinefelter syndrome (KS) described the increased morbidity and mortality in these subjects. Our aim was to study the structure and function of arteries in different districts to investigate in these subjects possible alterations. A total of 92 patients having non-mosaic KS, diagnosed in Centre for Human Reproduction Pathology at the University of Padova, and 50 age-matched healthy male controls were studied. Klinefelter syndrome subjects and controls evaluation included complete medical history, physical examination, measurement of concentrations of the reproductive hormones, lipidic and glycidic metabolism, AR function and sensitivity, ultrasound examinations (diameters, carotid intima-media thickness and brachial flow-mediated dilation) of brachial, common carotid and common femoral artery and abdominal aorta. Klinefelter syndrome patients showed significantly reduced artery diameters in all districts evaluated. On the contrary no statistically significant difference was found in cIMT and brachial FMD values between KS patients and controls. Furthermore, we found no statistically significant correlation of artery diameters with reproductive hormones, metabolic parameters, anthropometric measures and weighted CAG repeats. To our knowledge, this is the first study finding a reduced artery diameter in several districts in KS patients compared with that of normal male subjects and overlapping to that of female subjects. We have not an explanation for this phenomenon, even if a possible involvement of genes controlling the development of vascular system might be hypothesized, and further research is required to verify this hypothesis.
This article will be jointly published in the Journal of Andrology and the International Journal of Andrology. Andrology is the study of health issues specific to males, with a focus on basic aspects of their reproductive system (gonads, endocrine, and accessory organs), and diagnosis and treatment of medical problems associated with infertility, sexual dysfunction, and urological problems. In medicine, the development of Andrology as a specific specialty is rather recent; it had often been considered a subspecialty of urology or endocrinology. The field of Andrology, emerging over the past 40 years, has produced several specialty journals covering both the basic scientific and clinical areas. The International Journal of Andrology (IJA) began publication in 1978 and became the official journal of the European Academy of Andrology (EAA) in 1992. The American Society of Andrology (ASA) launched the Journal of Andrology (JA) in 1980. These 2 journals have been the leading journals in the field of Andrology, with current impact factors of 3.6 (IJA) and 3.1 (JA). Andrology remains a small and specialized field, and the size of both journals has been modest, each publishing about 600 pages per year. With the goal of increasing the visibility, impact, and prominence of both journals, and to better promote the field of Andrology, the EAA and ASA have decided jointly to create a single, even more prominent journal, Andrology. The international spirit of cooperation between the 2 societies and the enhanced availability of worldwide electronic communication has made it possible to jointly publish this new journal. The 2 societies will share equally in the management and editorial decisions of Andrology and in profits and losses from journal revenues and expenses. The 2 original journals will actively continue to publish throughout 2012, with the last issues being published as November/December 2012 issues. New papers submitted to these journals will be accepted for review through March 31, 2012. We encourage members of the 2 societies to continue to send their best work to JA or IJA so that we can keep the journals strong as we go into the merger. It is possible that some papers submitted to the original journals that need to be sent back to authors for significant revisions might not be accepted in time. If they are accepted later, they will appear in Andrology. Starting in late 2012, the back issues of both JA and IJA will be hosted on-line at the Wiley Online Library. The EAA and ASA are pleased to announce that a contract has been signed with Wiley-Blackwell, publisher of the IJA, for publication of Andrology. The journal will be published both in print and on-line, bimonthly, with accepted articles published on-line shortly after acceptance. We believe that there will be cost savings to both societies by eliminating duplications of effort in publishing and that the merged journal will result in increased profitability and income for the benefit of both societies. Ewa Rajpert-De Meyts, MD, PhD, of the Rigshospitalet of Copenhagen University, and Douglas Carrell, PhD, HCLD, of the University of Utah Medical School, have been chosen as Co-Editors-in-Chief. Members of the ASA (including trainees) and EAA will receive on-line subscriptions to Andrology with print subscriptions available at a modest extra charge. The greater distribution of the new journal will be a benefit to authors; also, society members will now have access to the content that would have been in separate journals. We believe that this larger, merged journal can more effectively compete with other journals and attract better articles. This more prominent journal should increase the prestige of the discipline of Andrology. Andrology will continue to publish basic, translational, clinical, and epidemiological research in andrology and will include all topics emphasized in both of the original journals. These include, among other areas, hormonal regulation, spermatogenesis, reproductive tract, accessory sex organs and external genitalia, sperm function and quality, prostate diseases including cancer, and male sexual physiology. Studies using mammalian and nonmammalian model systems and molecular and cellular investigations to understand male reproductive health and function in humans and important animal species will be considered. In addition, guidelines in clinical andrology and andrology laboratory science, as well as ASA and EAA society information, will appear in Andrology. Journal impact factors are published annually (June of each year) by the Institute for Scientific Information (ISI) in Thomson Reuters Journal Citation Reports. Although it will take several years for Andrology to fully establish its own impact factor, the combined impact factor of IJA and JA and Andrology can be computed to obtain an Impact Factor that authors can use to document the Impact of the Journal in which they are publishing. The June 2014 ISI Impact Factor report will list IJA and JA separately and represent the number of citations in 2013 to articles in the journals in 2011 and 2012 divided by the number of articles published in those 2 years; the numerators and denominators can be easily combined to calculate an overall impact for the 2 original journals. The 2015 ISI impact factor will list IJA, JA, and Andrology. For IJA and JA, the number will represent the citations in 2014 to articles published in 2012 divided by the number of articles published in that 1 year; for Andrology the impact factor will represent citations in 2014 to articles published in 2013 divided by the number of articles published in that 1 year. Again, an overall impact factor can be calculated by combining all 3 numerators and denominators. Thus, an effective impact factor of the original and merged journals can be obtained during the transition. From 2016 onward, only the impact factor of the new journal Andrology will appear in the ISI database. Based on our goals for the merged journal, strong support of ASA and EAA for the merger, and an outstanding Editorial and Publishing team, we expect the eventual impact factor of Andrology to surpass those previously achieved by JA and IJA. The first issue of Andrology will be published in January 2013. A submission site using the ScholarOne Manuscripts on-line submission and peer review system will be open at the start of April 2012 for submission of new manuscripts of original research in andrology. The Editors will be soliciting potentially outstanding review articles, and individuals with suggestions for reviews should contact one of the Editors-in-Chief. We encourage ASA and EAA members to support the launch of Andrology by submitting their best papers, especially during these most important first several years of the journal.
Previous studies suggest that male testosterone concentrations have declined over time. To explore this in a large US population, we examined testosterone and free testosterone concentrations in National Health and Nutrition Examination Surveys (NHANES) from 1988-1991 and 1999-2004. We also examined sex hormone-binding globulin (SHBG), estradiol, and androstanediol glucuronide (3α-diol-G) over the same period. Non-Hispanic white, non-Hispanic black, and Mexican-American men from 1988-1991 and 1999-2004 NHANES surveys who were ≥20 years old and had serum from morning blood draws were included in this analysis (1988-1991: N = 1,413; 1999-2004: N = 902). Testosterone, estradiol and SHBG were measured by competitive electrochemiluminescence immunoassays and 3α-diol-G was measured by enzyme immunoassay. Free testosterone was calculated using testosterone and SHBG values. Adjusted mean hormone concentrations were estimated using linear regression, accounting for NHANES sampling weights and design, age, race/ethnicity, body mass index, waist circumference, alcohol use and smoking. Differences in adjusted mean concentrations (Δ) and two-sided p-values were calculated; p < 0.05 was statistically significant. Overall, 3α-diol-G and estradiol declined between 1988-1991 and 1999-2004, but there was little change in testosterone, free testosterone, or SHBG (Δ: 3α-diol-G = -1.83 ng/mL, p < 0.01; estradiol = -6.07 pg/mL, p < 0.01; testosterone = -0.03 ng/mL, p = 0.75; free testosterone = -0.001 ng/mL, p = 0.67; SHBG = -1.17 nmol/L, p = 0.19). Stratification by age and race revealed that SHBG and 3α-diol-G declined among whites 20-44 years old (Δ: SHBG = -5.14 nmol/L, p < 0.01; 3α-diol-G = -2.89 ng/mL, p < 0.01) and free testosterone increased among blacks 20-44 years old (Δ: 0.014 ng/mL, p = 0.03). Estradiol declined among all ages of whites and Mexican-Americans. In conclusion, there was no evidence for testosterone decline between 1988-1991 and 1999-2004 in the US general population. Subgroup analyses suggest that SHBG and 3α-diol-G declined in young white men, estradiol declined in white and Mexican-American men, and free testosterone increased in young black men. These changes may be related to the increasing prevalence of reproductive disorders in young men.
The manner by which endocrine-disrupting xenobiotics, such as phthalates, can induce changes in the development of the male reproductive system still remains largely unknown. Herein, we have explored the application of ethane dimethane sulphonate (EDS) to eliminate adult-type Leydig cells in the mature rat testis, leading to their regeneration from resident stem cells, as a novel system to investigate the effects of dibutyl phthalate (DBP) and diethylstilbestrol (DES) on adult-type Leydig cell differentiation. The advantage of this model is that one can study adult-type Leydig cell differentiation in vivo divorced from the concomitant endocrine development of puberty. In these preliminary studies, we show that both DBP and/or DES, given for 2 or 4 days following EDS application, indeed affect Leydig cell differentiation in the adult testis, largely by increasing early Leydig cell proliferation and possibly thereby delaying early differentiation. In particular, on day 27 post-EDS, a time-point when the differentiation trajectory appears to be most discriminating, we observe that both DBP and/or DES cause a fourfold increase in Leydig cell density, and a significant increase in the expression of the Leydig cell-specific marker transcripts INSL3, LH receptor, Cyp17a1 and Cyp 11a1. In conclusion, both DBP and DES are able to affect adult-type Leydig cells during their differentiation to cause a significant perturbation in their ultimate functional capacity.
In men with non-obstructive azoospermia (NOA), the risk of hypogonadism is often overlooked. Testicular sperm extraction (TESE) may increase this risk. The objective of this study was to elucidate the prevalence of hypogonadism in NOA-patients, the impact of TESE on hormone balance and the association between testosterone deficiency and dyslipidaemia. Men with NOA who had undergone TESE during the period 2004-2009 were eligible. Hypogonadism was defined as total testosterone <10 nmol/L and/or LH >10 IU/L and/or ongoing androgen replacement therapy. Sixty-five consecutive men who had undergone TESE owing to NOA and from whom post-TESE serum testosterone levels measured before 1100 h were available. Furthermore, 141 fertile men served as controls. Serum concentrations of testosterone, LH and lipids were assessed. Odds ratios (OR) for biochemical hypogonadism were calculated. Pre- and post-TESE hormone levels were compared. Lipid profile was related to testosterone levels. Hypogonadism was found in 47% (95% CI, 0.36, 0.59) of the NOA-men. As compared with fertile controls, the OR for hypogonadism post-TESE was 17 (95% CI 6.6-45). Serum LH (p = 0.03), but not testosterone (p = 0.43), differed significantly pre- and post-TESE. Compared with eugonadal NOA-men, the OR for having deviations in lipid profile was 3.3 (95% CI 1.3-8.8) for the hypogonadal NOA-men. NOA-men are at very high risk of androgen deficiency, which even in young subjects is associated with dyslipidaemia. Medical management of these men should therefore include endocrinological evaluation and follow-up after completion of infertility treatment.
Fertilization, the recognition and fusion between spermatozoa and oocyte, involves various molecules on the spermatozoa and oocyte membranes. Concanavalin A (ConA)-binding proteins may be one of the molecules involved in mammal spermatozoa fertilization; however, their structure and function remain largely unknown. Here, we initially identified a ConA-binding protein, Zn-α2-glycoprotein (ZAG), involved in regulating the acrosome reaction (AR) of human spermatozoa. ZAG is localized on the pre-equatorial region covering the acrosome, neck and tail (some parts of middle piece and principal piece respectively) regions of the acrosome intact human spermatozoa, and disappears in the acrosomal region of the acrosome-reacted spermatozoa. Polyclonal antibodies against human recombinant ZAG significantly reduced the AR and sperm capability binding to human zona pellucida or penetration into zona-free hamster oocytes. Furthermore, assessment of the signaling pathways regulated by ZAG revealed that ZAG affects sperm AR through both the cAMP/PKA and PKC pathways. These results indicate that ZAG, which is present on the human sperm membrane, plays a critical role in the AR and subsequently, may be involved in sperm fertility.
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.
Germ cell tumours (GCTs) most often arise in the gonads, but some develop extragonadally. The aim of this study was to examine gender- and race-specific trends in incidence and survival of gonadal (GGCTs) and extragonadal GCTs (EGCTs) in the US from 1973 to 2007. We also examined the topographical distribution of EGCTs by race and gender. We estimated age-specific and age-standardized incidence rates and 5-year relative survival rates (RSR) of GCTs using the Surveillance, Epidemiology and End Results (SEER) Program (SEER nine registries). GCTs and their topographical sites were identified using ICD-O morphology and topography codes. Of 21,170 GCTs among males, 5.7% were extragonadal (Whites 5.5%; Blacks 16.3%). Of 2093 GCTs among females, 39.3% were extragonadal (Whites, 36.9%; Blacks 51.0%). The incidence of GGCT was much higher among White (56.3/1,000,000) than Black males (10.0/1,000,000), while there was no difference in incidence between White and Black females (3.2/1,000,000). The rates of EGCT among men and women of both races were similar (range:1.9-3.4/1,000,000). The most frequent extragonadal sites were mediastinum among males and placenta among females. The 5-year RSR of testicular GCT was higher among Whites (97%) than Blacks (90%), as was the 5-year RSR of ovarian GCT (Whites, 92%; Blacks 85%). In general, the 5-year RSRs of EGCTs were lower than the 5-year RSRs of GGCTs. The different incidence trends of GGCTs and EGCTs and distinct age-specific incidence patterns by anatomical site of EGCTs suggest that GGCTs and EGCTs may have different aetiologies.
