Journal Of Andrology[JOURNAL]
Sun
200 papers
The role of over-the-counter supplements for the treatment of male infertility--fact or fiction?
Ko EY, Sabanegh ES
J Androl · 2012 · PMID 21597088 · Publisher ↗
Many over-the-counter (OTC) vitamins and supplements have been used to improve male fertility. The purpose of this study is to review the effects of these OTC supplements on male fertility. A Pub Med and Medline review o...
Many over-the-counter (OTC) vitamins and supplements have been used to improve male fertility. The purpose of this study is to review the effects of these OTC supplements on male fertility. A Pub Med and Medline review of the randomized controlled studies utilizing OTC vitamins and supplements readily available in the United States over the last 3 decades was performed. Many studies demonstrate the positive effects of OTC supplementation on semen parameters and pregnancy outcomes. Conversely, many studies also demonstrate a lack of improvement and potential complications with supplementation. Confounding factors include lack of standard dosing regimens, duration of treatment, and control for dietary intake. No standard exists for which OTC supplement and vitamin studies have been conducted or the medications dosed. Definitive conclusions as to their true effects on male subfertility and dosing regimen could not be identified.
Ethnic variation in allele distribution of the androgen receptor (AR) (CAG)n repeat.
Ackerman CM, Lowe LP, Lee H … +6 more , Hayes MG, Dyer AR, Metzger BE, Lowe WL, Urbanek M, Hapo Study Cooperative Research Group
J Androl · 2012 · PMID 21597087 · Full text
The androgen receptor (AR) is important in reproductive organ development, as well as tissue homeostasis of the pancreas, liver, and skeletal muscle in adulthood. The trinucleotide (CAG)(n) repeat polymorphism in exon 1...
The androgen receptor (AR) is important in reproductive organ development, as well as tissue homeostasis of the pancreas, liver, and skeletal muscle in adulthood. The trinucleotide (CAG)(n) repeat polymorphism in exon 1 of the AR gene is thought to regulate AR activity, with longer alleles conferring reduced receptor activity. Therefore, the evaluation of the allelic distribution of the AR (CAG)(n) repeat in various ethnic groups is crucial in understanding the interindividual variability in AR activity. We evaluated ethnic variation of this AR polymorphism by genotyping individuals from the multiethnic Hyperglycemia and Adverse Pregnancy Outcome study cohort. We genotyped 4421 Caucasian mothers and 3365 offspring of European ancestry; 1494 Thai mothers and 1742 offspring; 1119 Afro-Caribbean mothers and 1142 offspring; and 780 Hispanic mothers and 770 offspring of Mexican ancestry from Bellflower, California. The distributions of (CAG)(n) alleles among all 4 ethnic groups are significantly different (P < .0001). Pairwise tests confirmed significant differences between each pair of ethnicities tested (P < 10(-28)). The relative AR (CAG)(n) repeat length in the different groups was as follows: Afro-Caribbean (shortest repeat lengths and greatest predicted AR activity) < Caucasian < Hispanic < Thai (longest repeat length and lowest predicted AR activity). Significant interethnic differences in the allele frequencies of the AR exon 1 (CAG)(n) polymorphism exist. Our results suggest that there may be potential ethnic differences in androgenic pathway activity and androgen sensitivity.
Hormonal imbalances and psychological scars left behind in infertile men.
Bak CW, Seok HH, Song SH … +3 more , Kim ES, Her YS, Yoon TK
J Androl · 2012 · PMID 21546616 · Publisher ↗
The effect of infertility on the psychological well-being of couples has been the subject of increasing attention in recent years. The frustration of couples of a relatively young age (ie, in their fourth decades) provok...
The effect of infertility on the psychological well-being of couples has been the subject of increasing attention in recent years. The frustration of couples of a relatively young age (ie, in their fourth decades) provokes not only anxiety and depression but also negative effects on the relationships. The objective of this study was to evaluate the effect of a diagnosis of male infertility on anxiety and depression in the men themselves and in fertile female spouses. The prospective cross-sectional study consisted of 264 participants, 72 males diagnosed with nonobstructive azoospermia (NOA) and their fertile spouses and 60 fertile couples attending our university between January 1, 2009, and April 30, 2010. The Beck Anxiety Inventory, Beck Depression Inventory (BDI), and hormone levels were measured during initial and follow-up visits. In NOA men, follicle-stimulating hormone and luteinizing hormone were positively associated with anxiety, in contrast to testosterone, which was inversely associated with anxiety. After the diagnosis of NOA, producing no testicular sperm, the panic intensity among men increased significantly, whereas their spouses exhibited less panic. By contrast, fertile female partners of NOA men reported higher BDI scores after the initial diagnosis of azoospermia, whereas their partners recorded higher levels of depression after the absence of testicular sperm was discovered. Insomnia was the most common complaint for both sexes after the diagnosis of azoospermia. Hormonal abnormalities had a negative effect on the quality of life. Physicians and clinicians should acknowledge the immense psychosocial effect of the diagnosis of male infertility on both males and their fertile female partners.
Genetic polymorphisms of glutathione S-transferase M1, T1, and P1, and the assessment of oxidative damage in infertile men with varicoceles from northwestern China.
Tang K, Xue W, Xing Y … +5 more , Xu S, Wu Q, Liu R, Wang X, Xing J
J Androl · 2012 · PMID 21546615 · Publisher ↗
Our objective was to investigate the genetic polymorphisms of the glutathione S-transferase M1, T1, and P1 genes (GSTM1, GSTT1, and GSTP1) and to assess the oxidative damage in infertile men with varicoceles from northwe...
Our objective was to investigate the genetic polymorphisms of the glutathione S-transferase M1, T1, and P1 genes (GSTM1, GSTT1, and GSTP1) and to assess the oxidative damage in infertile men with varicoceles from northwestern China. A total of 65 infertile men with varicoceles and 30 controls were included in the study. Multiplex polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism analyses were used to identify the genotypes. Sperm DNA damage was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL). The levels of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) were measured by high-performance liquid chromatography with electrochemical detection. The activities of malondialdehyde (MDA) and nitric oxide (NO), and the total antioxidant capacity (TAC) were detected by spectroscopic analysis, and sperm characteristics were measured using computer-assisted semen analysis. The frequencies of the GSTM1, GSTT1, and GSTP1 genotypes were not significantly different between the control and patient groups (P > .05). The percentage of TUNEL-positive sperm and the levels of 8-OH-dG, MDA, and NO were higher but the sperm concentration and motility and the TAC were lower in the patients with the GSTM1, GSTT1, and GSTM1/T1 null genotypes than those in the patients with the GSTM1, GSTT1, and GSTM1/T1 present genotypes (P < .05). However, no significant differences were observed between the GSTP1 A/A and A/G+G/G genotypes (P > .05). Our results suggest that the GSTM1 and GSTT1 null genotypes may predispose sperm to increased oxidative damage in infertile men with varicoceles; however, GSTP1 allelic variation was not significantly different between the patient and control groups in this study.
Identification of potential regulatory elements in the 5' and 3' UTRs of 12 translationally regulated mRNAs in mammalian spermatids by comparative genomics.
Chowdhury TA, Kleene KC
J Androl · 2012 · PMID 21546614 · Publisher ↗
To facilitate identifying translational control elements by studies of mutations in transgenic mice, a database of orthologous 5' and 3' ends of 12 messenger RNA (mRNA) species from 13 to 23 mammals that undergo delayed...
To facilitate identifying translational control elements by studies of mutations in transgenic mice, a database of orthologous 5' and 3' ends of 12 messenger RNA (mRNA) species from 13 to 23 mammals that undergo delayed translational activation in spermatids was constructed for the Acev2, Akap3, Akap4v2, Gapdhs, Odf1, Prm1, Prm2, Prm3, Smcp, Spata18, Tnp1, and Tnp2 mRNAs. This database, available here, was searched for conserved sequences in conserved positions and known translational control elements. Numerous potential mRNA-specific elements were identified, including upstream open reading frames, conserved sequences upstream and downstream of the poly(A) signal, and noncanonical and multiple poly(A) signals. RNA electrophoresis mobility shift assays demonstrate that Y-box proteins bind 30 of the 36 permutations of the degenerate Y-box recognition sequence (YRS), [UAC][CA]CA[UC]C[ACU], and this information was used to identify hundreds of YRSs in the untranslated region (UTR) database. Collectively, these findings suggest that the distal ends of both UTRs are particularly well conserved, implying that translation of each mRNA is regulated by mechanisms involving the poly(A) binding protein and the closed loop. In addition, the 5' flanking regions of all 12 genes have conserved, gene-specific sequences and configurations of elements that resemble the binding site of the testis-specific isoform of cyclic AMP response element modulator, and all 12 genes lack retrogene paralogues, demonstrating the efficacy of mechanisms that limit the proliferation of retroposons in the male germ line. This study illustrates the power of comparative genomics in identifying novel hypothetical regulatory elements for analysis with biochemical and in vivo genetic approaches.
Diagnosis and treatment of azoospermia resulting from testicular sarcoidosis.
Kovac JR, Flood D, Mullen JB … +1 more , Fischer MA
J Androl · 2012 · PMID 21546613 · Publisher ↗
Genitourinary sarcoidosis is uncommon, with only rare documented cases of testicular involvement reported. We detail the case of a 37-year-old male who initially presented for azoospermia and secondary infertility. A tes...
Genitourinary sarcoidosis is uncommon, with only rare documented cases of testicular involvement reported. We detail the case of a 37-year-old male who initially presented for azoospermia and secondary infertility. A testicular biopsy revealed nonnecrotizing granulomas and a chest x-ray identified perihilar lymphadenopathy and granulomatous lung nodules. A corticosteroid regimen was administered, and routine semen analyses were conducted. Significant improvements were noted after prednisone treatments. A successful in vivo fertilization was obtained. This is the first known case of testicular sarcoidosis diagnosed during investigations into azoospermia and secondary infertility which, after treatment with corticosteroids, resulted in natural fertilization.
Endothelial antioxidant compound prolonged the endothelial antiapoptotic effects registered after tadalafil treatment in patients with arterial erectile dysfunction.
La Vignera S, Condorelli R, Vicari E … +2 more , D'Agata R, Calogero AE
J Androl · 2012 · PMID 21546612 · Publisher ↗
This study evaluated the effects of a chronic treatment with tadalafil, a specific phosphodiesterase V inhibitor, on endothelial apoptosis through changes in the serum concentration of endothelial microparticles (EMP). E...
This study evaluated the effects of a chronic treatment with tadalafil, a specific phosphodiesterase V inhibitor, on endothelial apoptosis through changes in the serum concentration of endothelial microparticles (EMP). EMPs were arbitrarily chosen as a marker of endothelial apoptosis, and the changes in their concentration were monitored before and after treatment. Additionally, administration of endothelial antioxidant compound (EAC) during the follow-up, after discontinuation of tadalafil, was evaluated to determine whether this treatment improved the potential effects of tadalafil on the endothelium. Seventy-five patients with arterial erectile dysfunction were evaluated at baseline and after administration of tadalafil (5 mg once daily for 90 days). The International Index of Erectile Function questionnaire was administered, and penile dynamic Doppler and flow-cytometric (serum concentrations of EMPs) analyses were performed before (T0) and after treatment. Time points after tadalafil discontinuation: T1, after 1 week; T2, after 3 months; and T3, after 6 months. Three different schemes of follow-up were evaluated: group A, follow-up with EAC administration, after tadalafil discontinuation, for 6 months; group B, follow-up without other treatment; and group C, follow-up with placebo during the follow-up, after tadalafil cessation. The events CD45(neg)/CD144(pos)/annexinV(pos) were defined EMPs. Patients treated with tadalafil showed a significant decrease in serum EMPs 1 week after discontinuing tadalafil (16.4% ± 3.6% vs 7.1% ± 3.3%). This effect was maintained for up to 3 months in the group without other treatment during follow-up and was maintained for up to 6 months in the group treated with EAC during follow-up. Chronic treatment with tadalafil reduces endothelial apoptosis in patients with arterial erectile dysfunction. Further, EAC treatment prolongs and stabilizes the duration of antiapoptotic effects on the endothelium that are initially promoted by tadalafil treatment.
Paternal DNA damage resulting from various sperm treatments persists after fertilization and is similar before and after DNA replication.
Yamauchi Y, Riel JM, Ward MA
J Androl · 2012 · PMID 21546611 · Full text
In spite of its highly condensed state, sperm DNA is vulnerable to damage that can originate from oxidative stress, the activity of sperm-specific nucleases, or both. After fertilization, in the oocyte, paternal chromati...
In spite of its highly condensed state, sperm DNA is vulnerable to damage that can originate from oxidative stress, the activity of sperm-specific nucleases, or both. After fertilization, in the oocyte, paternal chromatin undergoes dramatic changes, and during this extensive remodeling, it can be both repaired and degraded, and these processes can be linked to DNA synthesis. Here, we analyzed sperm response to damage-inducing treatments both before and after fertilization and before or after zygotic DNA replication. Epididymal mouse spermatozoa were either frozen without cryoprotection (FT) or treated with detergent Triton X-100 coupled with dithiothreitol (TX+DTT) to induce DNA damage. Fresh, untreated sperm served as control. Immediately after preparation, spermatozoa from 3 groups were taken for comet assay, or for intracytoplasmic sperm injection into prometaphase I oocytes to visualize prematurely condensed single-chromatid chromosomes, or into mature metaphase II oocytes to visualize chromosomes after DNA replication. Comet assay revealed increased DNA fragmentation in treated sperm when compared with control, with FT sperm more severely affected. Chromosome analysis demonstrated paternal DNA damage in oocytes injected with treated, but not with fresh, sperm, with FT and TX+DTT groups now yielding similar damage. There were no differences in the incidence of abnormal paternal karyoplates before and after DNA synthesis in all examined groups. This study provides evidence that subjecting sperm to DNA damage-inducing treatments results in degradation of highly condensed sperm chromatin when it is still packed within the sperm head, and that this DNA damage persists after fertilization. The difference in DNA damage in sperm subjected to 2 treatments was ameliorated in the fertilized oocytes, suggesting that some chromatin repair might have occurred. This process, however, was independent of DNA synthesis and took place during oocyte maturation.
The value of transrectal ultrasound in the diagnosis of hematospermia in a large cohort of patients.
Zhao H, Luo J, Wang D … +4 more , Lu J, Zhong W, Wei J, Chen W
J Androl · 2012 · PMID 21512036 · Publisher ↗
Several studies have proved transrectal ultrasonography (TRUS) is efficient in the evaluation of patients with hematospermia, but the numbers of patients were less than 60 in each of the previous reports. Herein, a total...
Several studies have proved transrectal ultrasonography (TRUS) is efficient in the evaluation of patients with hematospermia, but the numbers of patients were less than 60 in each of the previous reports. Herein, a total of 270 patients with hematospermia were evaluated by TRUS to assess its efficacy in the etiologic diagnosis of hematospermia. The age of patients ranged from 15 to 75 years (x, 41.2 years), and the duration of symptoms was 1 day to 8 years (x, 3.4 months). Abnormalities were revealed by TRUS in 256 patients (94.8%). The percentages of pathological conditions located in the seminal vesicles, in the ejaculatory ducts, in the prostate, and in the bladder were 46.3% (125 cases), 29.6% (80 cases), 55.2% (149 cases), and 0.4% (1 case), respectively. The number of patients older than 40 years old and 40 years old or younger were 126 and 144, respectively. Our results show significantly higher percentages for malignant diseases, prostatic calcification and benign prostatic hyperplasia in the group of patients more than 40 years old compared with the group of patients 40 years old or less. Eight of 270 patients (3.0%) had malignant tumors, and all of the 8 malignancies occurred in patients more than 40 years old. TRUS is a noninvasive, reliable tool for the investigation of causes of hematospermia. Hematospermia is generally a benign symptom in younger patients. Special attention should be paid to elderly patients to exclude malignancy.
Varicocelectomy does not impact pregnancy outcomes following intracytoplasmic sperm injection procedures.
Pasqualotto FF, Braga DP, Figueira RC … +3 more , Setti AS, Iaconelli A, Borges E
J Androl · 2012 · PMID 21474792 · Publisher ↗
There are many studies in the literature suggesting an acquired, apparently progressive infertility due to varicocele. In fact, varicocelectomy has become the most commonly performed male infertility surgery. Assisted re...
There are many studies in the literature suggesting an acquired, apparently progressive infertility due to varicocele. In fact, varicocelectomy has become the most commonly performed male infertility surgery. Assisted reproductive technologies such as intracytoplasmic sperm injection (ICSI) are also important for couples with male factor infertility associated with varicocele. Therefore, the aim of this study was to evaluate the effect of varicocelectomy on sperm quality and pregnancy rate with ICSI. Data were analyzed from 248 patients who had varicocele or underwent a previous varicocelectomy and were treated with ICSI between 2000 and 2008. Patients with varicocele were divided into two groups: men with clinical varicocele (group 1, n = 79) and men who underwent varicocelectomy before ICSI (group 2, n = 169). In all cases, female infertility was not detected. We evaluated and compared the two groups' semen characteristics as defined by the World Health Organization and Tygerberg's strict criteria: the female partner's age; the number of oocytes retrieved; and the fertilization, implantation, pregnancy, and miscarriage rates. We used the Wilcoxon signed rank test or the Mann-Whitney test for these analyses. No differences were detected in the age of the female partners between group 1 (33.0 ± 0.46 years) and group 2 (33.8 ± 0.38 years; P = .1872). Semen volume was higher in group 1 (3.3 ± 0.3 mL) than it was in group 2 (2.5 ± 0.14; P = .0043). No differences were detected between groups 1 and 2 with regard to sperm concentration (30.08 ± 4.01 million/mL and 24.1 ± 2.42 million/mL, respectively; P = .138), sperm motility (38.2% ± 2.69% and 38.7% ± 2.08%, respectively; P = .881), and morphology according to Tygerberg's strict criteria (2.6% ± 0.44% and 2.4% ± 0.37%, respectively; P = .7202). Also, no differences were detected in the number of oocytes retrieved between group 1 (14.8 ± 1.74) and group 2 (14.9 ± 1.04; P = .9515). The fertilization rate was higher in group 1 (73.2%) than it was in group 2 (64.9%; P = .0377); however, no differences were detected in the pregnancy rates (31.1% vs 30.9%; P = .9806), implantation rates (22.1% vs 17.3%; P = .5882), or miscarriage rates (21.7% vs 23.9%; P = .8401) between groups 1 and 2. Although a varicocelectomy should always be performed before assisted reproduction is pursued, this surgery does not increase pregnancy rates or decrease miscarriage rates following ICSI.
Trajectory variance and autocorrelations within single-sperm tracks as population-level descriptors of sperm track complexity, predictability, and energy-generating ability.
Abaigar T, Barbero J, Holt WV
J Androl · 2012 · PMID 21474791 · Publisher ↗
The objectives of the present study were to develop an alternative theoretical approach to the analysis of sperm motility and to develop motility parameters that would complement those more commonly used in current compu...
The objectives of the present study were to develop an alternative theoretical approach to the analysis of sperm motility and to develop motility parameters that would complement those more commonly used in current computer-assisted semen analysis procedures. We have defined a set of parameters and have tested them using boar spermatozoa undergoing bicarbonate-induced motility activation. The new parameters were calculated for a series of (x,y) coordinates of sperm head positions recorded at each move along the trajectory. The parameters were: mean velocity (MV), immobility ratio, fractal dimension (FD), the variance of the steplengths (VAR), and 2 autocorrelation function coefficients of the step-length time series for lags 1 and 2 (C(1) and C(2)). MV measures the average speed along the trajectory, and VAR is a measure of displacement variability that can be related to the specific mean (per step) kinetic energy of the spermatozoon. All of the parameters except MV and FD were affected by the sampling frequency (25 vs 50 Hz); inappropriately high sampling frequency in relation to magnification resulted in step-lengths between successive frames that were below the resolution threshold of the imaging system. The autocorrelation functions were especially informative; discrimination between sperm subpopulations was obvious within simple histogram formats, and complex statistical analyses were not needed for their identification.
Chronic pain has a negative impact on sexuality in testis cancer survivors.
Pühse G, Wachsmuth JU, Kemper S … +3 more , Husstedt IW, Evers S, Kliesch S
J Androl · 2012 · PMID 21474790 · Publisher ↗
Testis cancer is a disease that directly affects a man's sense of masculinity and involves treatments compromising sexual function. The aim of this study was to investigate the prevalence of sexual dysfunction and the in...
Testis cancer is a disease that directly affects a man's sense of masculinity and involves treatments compromising sexual function. The aim of this study was to investigate the prevalence of sexual dysfunction and the influence of chronic pain on sexuality in long-term testis cancer survivors. Thus, we examined 539 patients after they had one testis removed because of a testicular germ cell tumor. Having completed oncologic therapy, all patients received a detailed questionnaire asking about the occurrence and clinical presentation of testis pain before and after orchiectomy. In addition, items from the abridged International Index of Erectile Function and Brief Sexual Function Inventory were used to gain precise information on individual sexual function. Overall, 34.5% of our testicular cancer survivors complained of reduced sexual desire, and sexual activity was reduced in 41.6%. Erectile dysfunction was present in up to 31.5% of patients. In 24.4%, the ability to maintain an erection during intercourse was impaired. Ejaculatory disorders (premature, delayed, retrograde, or anejaculation) occurred in 84.9% of our testis cancer survivors. A total of 32.4% of our participants experienced a reduced intensity of orgasm, and 95.4% experienced reduced overall sexual satisfaction. There was a significant correlation between the occurrence of chronic pain symptoms and the relative frequency and intensity of erectile dysfunction, inability to maintain an erection, ejaculation disorders, and reduced intensity of orgasm. In conclusion, chronic pain has a negative impact on sexuality in testis cancer survivors.
The composition and structure of stones in enlarged prostatic utricles (EPU).
Cai T
J Androl · 2012 · PMID 21474789 · Publisher ↗
Abstract loading — click title to view on PubMed.
Circulating endothelial progenitor cells and endothelial microparticles in patients with arterial erectile dysfunction and metabolic syndrome.
La Vignera S, Condorelli R, Vicari E … +2 more , D'Agata R, Calogero AE
J Androl · 2012 · PMID 21474787 · Publisher ↗
Blood endothelial progenitor cells (EPC) and microparticles (EMP) have been proposed as markers of endothelial dysfunction. The aim of this study was to evaluate both EPCs and EMPs in patients with arterial erectile dysf...
Blood endothelial progenitor cells (EPC) and microparticles (EMP) have been proposed as markers of endothelial dysfunction. The aim of this study was to evaluate both EPCs and EMPs in patients with arterial erectile dysfunction (ED) and metabolic syndrome (MetS). To accomplish this, 100 patients (ages 45-60 years) with ED and MetS (Adult Treatment Panel III [ATP III] 1999 criteria) and 17 healthy men (ages 44-57 years) were selected. EPC (CD45(neg)/CD34(pos)/CD144(pos)) and EMP (CD45(neg)/CD144(pos)/Annexin V(pos)) blood concentrations were evaluated by flow cytometry, before and after administration of tadalafil (20 mg) on demand for 3 months. Before treatment, EPCs and EMPs were significantly higher in patients compared with healthy men. EPCs increased significantly after tadalafil administration, whereas EMPs did not differ significantly. EPCs correlated positively or negatively with body mass index and with some cavernous artery indices, both before and after tadalafil administration. EMPs showed only positive correlations with body mass index and some cavernous artery indices, both before and after tadalafil administration. Patients with arterial ED and MetS have higher EPCs and EMPs compared with healthy men; hence, these cells may be regarded as markers of cavernous artery dysfunction. Tadalafil administration increased EPCs but not EMPs, suggesting that this compound may play a role in the endothelial repair response.
Reexamination of pharmacokinetics of oral testosterone undecanoate in hypogonadal men with a new self-emulsifying formulation.
Yin AY, Htun M, Swerdloff RS … +11 more , Diaz-Arjonilla M, Dudley RE, Faulkner S, Bross R, Leung A, Baravarian S, Hull L, Longstreth JA, Kulback S, Flippo G, Wang C
J Androl · 2012 · PMID 21474786 · Full text
Many hypogonadal men prefer oral testosterone (T) treatment. Oral T undecanoate (TU) is available in many countries, but not in the United States. We aimed to assess the pharmacokinetics of oral TU in a new self-emulsify...
Many hypogonadal men prefer oral testosterone (T) treatment. Oral T undecanoate (TU) is available in many countries, but not in the United States. We aimed to assess the pharmacokinetics of oral TU in a new self-emulsifying drug delivery system formulation. Pharmacokinetics studies were conducted in 3 parts: 12 hypogonadal men were enrolled in 2 centers for a 1-day dosing study; 29 participants were enrolled from 3 centers for a 7-day dosing study; and 15 participants were enrolled from 1 center for a 28-day dosing study. Serial blood samples for serum sex hormone measurements by liquid chromatography-tandem mass spectrometry were drawn for up to 36 hours after oral TU administration. Mean serum T levels (C(avg)) after oral dosing of T 200 mg as TU twice daily with food were within the adult male range in most participants in the 1-, 7-, and 28-day dosing studies but were much lower in the fasting state. The dose-proportional increase in C(avg) of serum T after oral T 300 mg twice daily resulted in more participants with supraphysiologic serum T levels. In the 28-day study, trough serum T reached a steady state at day 7. Serum dihydrotestosterone and estradiol levels tracked serum T concentration. Dihydrotestosterone-testosterone ratios increased 3-fold after oral TU administration. Oral T 200 mg twice daily as TU in a new SEDDS formulation may be a viable therapy for hypogonadal men.
Diabetes mellitus and sperm parameters.
La Vignera S, Condorelli R, Vicari E … +2 more , D'Agata R, Calogero AE
J Androl · 2012 · PMID 21474785 · Publisher ↗
Because of the paucity of studies and inconsistencies regarding the impact of diabetes mellitus (DM) on semen quality, this disease is seldom looked for in the infertile patient. Recently, this view has been challenged b...
Because of the paucity of studies and inconsistencies regarding the impact of diabetes mellitus (DM) on semen quality, this disease is seldom looked for in the infertile patient. Recently, this view has been challenged by findings showing that DM induces subtle molecular changes that are important for sperm quality and function. This brief review shows the main sperm parameters in patients with DM and presents the mechanisms hypothesized to explain the changes observed in these patients. The data available suggest that DM alters conventional sperm parameters. In addition, DM causes histologic damage of the epididymis, with a negative impact on sperm transit. Various mechanisms may explain the sperm damage observed in patients with DM. These include endocrine disorders, neuropathy, and increased oxidative stress. Many authors suggest that DM decreases serum testosterone levels. This is associated with a steroidogenetic defect in Leydig cells. In addition, diabetic neuropathy seems to cause atonia of seminal vesicles, bladder, and urethra. Furthermore, DM is associated with an increased oxidative stress, which damages sperm nuclear and mitochondrial DNA. Finally, spermatogenesis derangement and germ cell apoptosis in type 1 DM may relate to a local autoimmune damage, whereas insulin resistance, obesity, and other related comorbidities may impair sperm parameters and decrease testosterone serum levels in patients with type 2 DM.
Memorial: Dr JoGayle Howard.
Pukazhenthi B
J Androl · 2011 · PMID 21474784 · Publisher ↗
Abstract loading — click title to view on PubMed.
Gene expression in the epididymis of normal and vasectomized men: what can we learn about human sperm maturation?
Sullivan R, Legare C, Thabet M … +1 more , Thimon V
J Androl · 2011 · PMID 21441430 · Publisher ↗
Anatomically, the human epididymis is unusual when compared with the excurrent duct of other eutherian mammals. Furthermore, clinical observations suggest that it may not be as important for sperm maturation as is the ca...
Anatomically, the human epididymis is unusual when compared with the excurrent duct of other eutherian mammals. Furthermore, clinical observations suggest that it may not be as important for sperm maturation as is the case for laboratory animals. In contrast, hierarchical clustering of microarray data of epididymides from normal men revealed 2274 modulated qualifiers between the epididymal segments, 1184, 713, and 269 of them being highly expressed in the caput, corpus, and cauda, respectively. The organization of qualifiers according to their similarities by gene ontology indicated that caput transcripts are dedicated to cell-cell adhesion, whereas the corpus is characterized by genes involved in response to other organisms (ie, defense mechanisms) and the cauda transcriptome is specialized in muscle contraction and establishment of localization. A region-specific gene expression pattern thus characterizes the human epididymis as in animal models. In humans, vasectomies have consequences on the epididymal transcriptome. Cluster analysis revealed that 1363 genes are expressed in both normal and vasectomized epididymides, whereas 911 and 660 of them are specifically expressed in normal and vasectomized epididymides, respectively. Three of the affected genes are particularly interesting because of their involvement in sperm biochemical remodeling during epididymal transit: dicarbonyl/l-xylulose reductase, Niemann-Pick disease, type C2, and cysteine-rich secretory protein 1. In some vasovasostomized men, these modifications in gene expression induced by vasectomy are irreversible, thus affecting the biochemical parameters, and potentially, the function of their ejaculated sperm. This may explain the discrepancies between a surgically successful vasovasostomy and fertility recovery.
Monotremes provide a key to understanding the evolutionary significance of epididymal sperm maturation.
Nixon B, Ecroyd HW, Dacheux JL … +1 more , Jones RC
J Androl · 2011 · PMID 21441429 · Publisher ↗
It has been widely accepted that mammalian spermatozoa are infertile when they leave the testes and require a period of maturation in both the epididymis and the female reproductive tract before acquiring the ability to...
It has been widely accepted that mammalian spermatozoa are infertile when they leave the testes and require a period of maturation in both the epididymis and the female reproductive tract before acquiring the ability to fertilize an oocyte. However, the necessity for such a complex process of posttesticular sperm maturation appears to be unique to mammals because it is well established that these processes do not directly influence the fertilizing ability of the spermatozoa of birds, reptiles, and other lower vertebrates. Because of their key evolutionary position and form of reproduction, we contend that monotremes (platypus and echidna) provide a unique model for resolving why these processes are necessary. In the present review, we examine evidence that the epididymal maturation of monotreme spermatozoa is far less complex than in other mammals. However, a unique feature of the monotreme epididymis lies in its ability to promote the formation of elaborate sperm bundles that serve to greatly enhance the cells' motility. It is suggested that this intriguing cooperative strategy used by monotreme sperm represents an early form of epididymal maturation that appears to have been elaborated upon during the evolution of higher mammals, possibly as an adaptation for sperm competition.
Epididymal protein targets: a brief history of the development of epididymal protease inhibitor as a contraceptive.
O'Rand MG, Widgren EE, Hamil KG … +2 more , Silva EJ, Richardson RT
J Androl · 2011 · PMID 21441428 · Publisher ↗
The Laboratories for Reproductive Biology at the University of North Carolina at Chapel Hill began collaboration with Human Genome Sciences (Rockville, Maryland) to sequence a human epididymal library and identify epidid...
The Laboratories for Reproductive Biology at the University of North Carolina at Chapel Hill began collaboration with Human Genome Sciences (Rockville, Maryland) to sequence a human epididymal library and identify epididymal-specific genes. Among the first clones obtained from Human Genome Sciences was a clone for EPPIN (official symbol, SPINLW1). Our laboratory has described EPPIN (epididymal protease inhibitor) as a novel gene on human chromosome 20q12-13.2 that encodes a cysteine-rich protein containing both Kunitz-type and WAP-type 4-disulfide core consensus sequences that characterize it as a protease inhibitor. EPPIN expresses 3 mRNA splice variants that encode 2 protein isoforms found in the testis and epididymis. Of the 2 isoforms, 1 is secreted and 1 lacks a secretory signal piece. EPPIN is predominantly a dimer, although multiples often exist, and in its native form, EPPIN is found on the sperm surface complexed with lactotransferrin and clusterin. During ejaculation, semenogelin from the seminal vesicles is bound to the EPPIN protein complex, initiating a series of events that define EPPIN's function: modulating prostate-specific antigen (PSA) activity, providing antimicrobial protection, and binding semenogelin, thereby inhibiting sperm motility. As PSA hydrolyzes semenogelin in the ejaculate coagulum, spermatozoa gain progressive motility. Using immunization as a tool to study antigen function, we demonstrated that EPPIN is essential for fertility because immunization of male monkeys with recombinant EPPIN results in complete, but reversible, contraception. To exploit our understanding of EPPIN's function, we have developed a high-throughput screen to look for compounds that inhibit EPPIN-semenogelin interaction and mimic anti-EPPIN, inhibiting sperm motility. These compounds are now being developed into a nonhormonal male contraceptive.
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