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Genetic and epigenetic risks of intracytoplasmic sperm injection method.

Ioannis GEORGIOU ; Maria SYRROU ; Nicolaos PARDALIDIS ; Konstantinos KARAKITSIOS ; Themis MANTZAVINOS ; Nikolaos GIOTITSAS ; Dimitrios LOUTRADIS ; Fotis DIMITRIADIS ; Motoaki SAITO ; Ikuo MIYAGAWA ; Pavlos TZOUMIS ; Anastasios SYLAKOS ; Nikolaos KANAKAS ; Theodoros MOUSTAKAREAS ; Dimitrios BALTOGIANNIS ; Stavros TOULOUPIDES ; Dimitrios GIANNAKIS ; Michael FATOUROS ; Nikolaos SOFIKITIS

Asian Journal of Andrology.2006;8(6):643-673.

Pregnancies achieved by assisted reproduction technologies, particularly by intracytoplasmic sperm injection (ICSI) procedures, are susceptible to genetic risks inherent to the male population treated with ICSI and additional risks inherent to this innovative procedure. The documented, as well as the theoretical, risks are discussed in the present review study. These risks mainly represent that consequences of the genetic abnormalities underlying male subfertility (or infertility) and might become stimulators for the development of novel approaches and applications in the treatment of infertility. In addition, risks with a polygenic background appearing at birth as congenital anomalies and other theoretical or stochastic risks are discussed. Recent data suggest that assisted reproductive technology might also affect epigenetic characteristics of the male gamete, the female gamete, or might have an impact on early embryogenesis. It might be also associated with an increased risk for genomic imprinting abnormalities.
Animals ; Child, Preschool ; Chromosome Aberrations ; Chromosome Deletion ; Congenital Abnormalities ; genetics ; Epigenesis, Genetic ; Female ; Genomic Imprinting ; HIV Infections ; transmission ; Haploidy ; Humans ; Infant ; Infectious Disease Transmission, Vertical ; Infertility, Male ; genetics ; Klinefelter Syndrome ; genetics ; Male ; Pregnancy ; Preimplantation Diagnosis ; Risk ; Sex Chromosome Aberrations ; Sperm Injections, Intracytoplasmic ; adverse effects ; Spermatogenesis ; genetics ; Translocation, Genetic ; genetics ; X Chromosome ; genetics ; XYY Karyotype ; genetics

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Pathophysiology and treatment of diabetic erectile dysfunction.

Charles R MOORE ; Run WANG

Asian Journal of Andrology.2006;8(6):675-684.

The pathophysiology of diabetes is multifactorial and no single etiology is at the forefront. The proposed mechanisms of erectile dysfunction (ED) in diabetic patients includes elevated advanced glycation end-products (AGEs) and increased levels of oxygen free radicals, impaired nitric oxide (NO) synthesis, increased endothelin B receptor binding sites and ultrastructural changes, upregulated RhoA/Rho-kinase pathway, NO-dependent selective nitrergic nerve degeneration and impaired cyclic guanosine monophosphate (cGMP)-dependent kinase-1 (PKG-1). The treatment of diabetic ED is multimodal. Treatment of the underlying hyperglycemia and comorbidities is of utmost importance to prevent or halt the progression of the disease. The peripherally acting oral phosphodiesterase type 5 (PDE5) inhibitors are the mainstay of oral medical treatment of ED in diabetics. Vacuum erection devices are an additional treatment as a non-invasive treatment option. Local administration of vasoactive medication via urethral suppository or intracorporal injection can be effective with minimal side-effects. Patients with irreversible damage of the erectile mechanism are candidates for penile implantation. Future strategies in the evolution of the treatment of ED are aimed at correcting or treating the underlying mechanisms of ED. With an appropriate vector, researchers have been able to transfect diabetic animals with agents such as neurotrophic factors and nitric oxide synthase (NOS). Further studies in gene therapy are needed to fully ascertain its safety and utility in humans.
Alprostadil ; administration & dosage ; therapeutic use ; Cyclic GMP-Dependent Protein Kinases ; physiology ; Diabetes Complications ; physiopathology ; Diabetic Neuropathies ; physiopathology ; Erectile Dysfunction ; etiology ; physiopathology ; therapy ; Glycation End Products, Advanced ; physiology ; Humans ; Male ; Nitric Oxide ; physiology ; Penile Erection ; Penile Prosthesis ; Penis ; blood supply ; Phosphodiesterase Inhibitors ; therapeutic use ; Receptor, Endothelin B ; physiology ; Suppositories ; Vacuum

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Persistent Muellerian duct syndrome with transverse testicular ectopia.

Yue-You LIANG ; Fu-Fu ZHENG ; Yu-Ping DAI ; Ke-Li ZHENG ; Jie-Xue ZHOU

Asian Journal of Andrology.2006;8(6):745-747.

Persistent Muellerian duct syndrome (PMDS) is a rare form of male pseudohermaphrodism without the feature of ambiguous genitalia. We present a case of PMDS with transverse testicular ectopia (TTE).
Abnormalities, Multiple ; Adult ; Disorders of Sex Development ; pathology ; surgery ; Hernia, Inguinal ; surgery ; Humans ; Male ; Mullerian Ducts ; abnormalities ; surgery ; Testicular Hydrocele ; surgery ; Testis ; abnormalities ; surgery

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Cross-sectional and longitudinal studies on interaction between bladder compliance and outflow obstruction in men with benign prostatic hyperplasia.

Li-Min LIAO ; Werner SCHAEFER

Asian Journal of Andrology.2007;9(1):51-56.

AIMTo explore the interaction between bladder compliance (BC) and bladder outflow obstruction (BOO) in men with benign prostatic hyperplasia (BPH) using cross-sectional and longitudinal studies.

METHODSA total of 181 men with BPH were recruited, and 100 of them were followed for one year. Cystometry was performed in a standing or a sitting position with 30 mL/min infusion. BC was manually corrected and defined. Obstruction coefficient (OCO), linear passive urethral resistance relation and international continence society (ICS) nomogram were used to diagnose BOO. The obstructed parameters were compared between the reduced BC group and the non-reduced group. BC was compared between the first investigation at the beginning of study and the second investigation at the end of study during the one-year follow-up period.

RESULTSThe group with reduced BC had increased OCO and linear passive urethral resistance relation. BC was significantly lower in the obstructed group (55.7 mL/cm water) than that in unobstructed and equivocal one (74.9 mL/cm water, P <0.01). BC gradually reduced with the increased obstructed grade. There was a significantly weak negative correlation between BC and OCO (r = -0.132, P < 0.01). Over the one-year follow-up period in the longitudinal study, BC for all men changed from 54.4 to 48.8 mL/cm water (P >0.05), and BC for the group with BOO fell from 58.4 +/- 70.1 to 46.5 +/- 38.7 mL/cm water (P>0.05).

CONCLUSIONIn men with BPH, a significant systematic decrease occurred in BC in the obstructed group and a significant systematic increase with urethral resistance occurred in the low BC group. A longitudinal study of the tendency of BC reduction in a group with BOO is necessary in the future.

Adult ; Aged ; Aged, 80 and over ; Compliance ; Cross-Sectional Studies ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Prostatic Hyperplasia ; physiopathology ; Ureteral Obstruction ; physiopathology ; Urinary Bladder ; physiopathology

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Gene therapy and erectile dysfunction: the current status.

David H W LAU ; Sashi S KOMMU ; Emad J SIDDIQUI ; Cecil S THOMPSON ; Robert J MORGAN ; Dimitri P MIKHAILIDIS ; Faiz H MUMTAZ

Asian Journal of Andrology.2007;9(1):8-15.

Current available treatment options for erectile dysfunction (ED) are effective but not without failure and/or side effects. Although the development of phosphodiesterase type 5 (PDE5) inhibitors (i.e. sildenafil, tadalafil and vardenafil) has revolutionized the treatment of ED, these oral medications require on-demand access and are not as effective in treating ED related to diabetic, post-prostatectomy and severe veno-occlusive disease states. Improvement in the treatment of ED is dependent on understanding the regulation of human corporal smooth muscle tone and on the identification of relevant molecular targets. Future ED therapies might consider the application of molecular technologies such as gene therapy. As a potential therapeutic tool, gene therapy might provide an effective and specific means for altering intracavernous pressure "on demand" without affecting resting penile function. However, the safety of gene therapy remains a major hurdle to overcome before being accepted as a mainstream treatment for ED. Gene therapy aims to cure the underlying conditions in ED, including fibrosis. Furthermore, gene therapy might help prolong the efficacy of the PDE5 inhibitors by improving penile nitric oxide bioactivity. It is feasible to apply gene therapy to the penis because of its location and accessibility, low penile circulatory flow in the flaccid state and the presence of endothelial lined (lacunar) spaces. This review provides a brief insight of the current role of gene therapy in the management of ED.
3',5'-Cyclic-GMP Phosphodiesterases ; antagonists & inhibitors ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Erectile Dysfunction ; drug therapy ; genetics ; therapy ; Gene Transfer Techniques ; Genetic Therapy ; adverse effects ; Humans ; Male ; Phosphodiesterase Inhibitors ; therapeutic use ; Vasodilator Agents ; therapeutic use

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Dual androgen-response elements mediate androgen regulation of MMP-2 expression in prostate cancer cells.

Ben-Yi LI ; Xin-Bo LIAO ; Atsuya FUJITO ; J Brantley THRASHER ; Fang-Yun SHEN ; Ping-Yi XU

Asian Journal of Andrology.2007;9(1):41-50.

AIMTo characterize the matrix metalloproteinases (MMP)-2 promoter and to identify androgen response elements (AREs) involved in androgen-induced MMP-2 expression.

METHODSMMP-2 mRNA levels was determined by reverse transcription-polymerase chain reaction (RT-PCR). MMP-2 promoter-driven luciferase assays were used to determine the fragments responsible for androgen-induced activity. Chromatin-immunoprecipitation assay and electrophoretic mobility shift assays (EMSA) were used to verify the identified AREs in the MMP-2 promoter.

RESULTSAndrogen significantly induced MMP-2 expression at the mRNA level, which was blocked by the androgen antagonist bicalutamide. Deletion of a region encompassing base pairs -1591 to -1259 (relative to the start codon) of the MMP-2 promoter led to a significant loss of androgen-induced reporter activity. Additional deletion of the 5'-region up to -562 bp further reduced the androgen-induced MMP-2 promoter activity. Sequence analysis of these two regions revealed two putative ARE motifs. Introducing mutations in the putative ARE motifs by site-directed mutagenesis approach resulted in a dramatic loss of androgen-induced MMP-2 promoter activity, indicating that the putative ARE motifs are required for androgen-stimulated MMP-2 expression. Most importantly, the androgen receptor (AR) interacted with both motif-containing promoter regions in vivo in a chromatin immunoprecipitation assay after androgen treatment. Furthermore, the AR specifically bound to the wild-type but not mutated ARE motifs-containing probes in an in vitro EMSA assay.

CONCLUSIONTwo ARE motifs were identified to be responsible for androgen-induced MMP-2 expression in prostate cancer cells.

Androgens ; pharmacology ; Cell Line, Tumor ; Chromatin ; genetics ; DNA Primers ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Genes, Reporter ; Humans ; Luciferases ; genetics ; Male ; Matrix Metalloproteinase 2 ; genetics ; metabolism ; Mutagenesis, Site-Directed ; Promoter Regions, Genetic ; Prostatic Neoplasms ; enzymology ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Deletion

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Pressure-flow studies in patients with benign prostatic hyperplasia: a study comparing suprapubic and transurethral methods.

Shan-Chao ZHAO ; Shao-Bin ZHENG ; Wan-Long TAN ; Peng ZHANG ; Huan QI

Asian Journal of Andrology.2006;8(6):731-735.

AIMTo compare the use of the suprapubic puncture method versus the transurethral method in pressure-flow studies in patients with benign prostatic hyperplasia.

METHODSTwenty-three men with benign prostatic hyperplasia underwent both suprapubic and transurethral pressure-flow studies during a single session. Standard pressure-flow variables were recorded in all patients with both methods, enabling calculation of obstruction using commonly used grading systems, such as the urethral resistance algorithm, the Abrams-Griffith (AG) number and the Schaer linear nomogram.

RESULTSThere were statistically significant differences between the methods in the mean values of maximum flow rate (P < 0.05), detrusor pressure at the maximum flow (P < 0.01), urethral resistance algorithm (P < 0.01), AG number (P < 0.01) and maximum cystic capacity (P < 0.01). Of the men in the study, 10 (43.5%) remained in the same Schaer class with both methods and 18 (78.3%) in the same AG number area. Using the transurethral method, 12 (52.2%) men increased their Schaer class by one and 1 (4.3%) by two. There were also differences between the suprapubic and transurethral methods using the AG number: 4 (17.4%) men moved from a classification of equivocal to obstructed and 1 (4.3%) from unobstructed to equivocal.

CONCLUSIONThe differences between the techniques for measuring intravesical pressure alter the grading of obstruction determined by several of the commonly used classifications. An 8 F transurethral catheter significantly increases the likelihood of a diagnosis of bladder outlet obstruction when compared with the suprapubic method.

Aged ; Humans ; Male ; Middle Aged ; Pressure ; Prostatic Hyperplasia ; physiopathology ; Punctures ; Urinary Bladder Neck Obstruction ; diagnosis ; Urinary Catheterization ; Urination ; physiology ; Urodynamics

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The clinical curative effect of transurethral resection of the ejaculatory duct for iatrogenic ejaculatory duct obstruction after prostatic hyperthermia.

Liang-Yun ZHAO ; Xiang-An TU ; Chun-Hua DENG

Asian Journal of Andrology.2006;8(6):755-756.

Adult ; Ejaculatory Ducts ; surgery ; Genital Diseases, Male ; surgery ; Humans ; Hyperthermia, Induced ; adverse effects ; Iatrogenic Disease ; Infertility, Male ; etiology ; Male ; Prostatitis ; therapy ; Urethra

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Can inhibin-B predict the outcome of microsurgical epididymal sperm aspiration in patients with suspected primary obstructive azoospermia.

Marij SMIT ; Gert R DOHLE ; Mark F WILDHAGEN ; Rob F A WEBER

Asian Journal of Andrology.2007;9(3):382-387.

AIMTo evaluate whether inhibin-B can predict the outcome of a microsurgical epidymal sperm aspiration (MESA) procedure in patients with suspected primary obstructive azoospermia (OA) and if inhibin-B can replace testicular biopsy in the diagnostic work-up of these patients.

METHODSInhibin-B levels and testicular biopsy scores were related to the outcome of MESA in 43 patients with suspected primary OA. MESA was considered to be successful when epididymal sperm could be identified during the procedure.

RESULTSSpermatozoa were present in the epididymal aspirate in 28 out of the 43 patients (65%). Inhibin-B values were not significantly different in patients with successful or unsuccessful MESA. The modified Johnsen score, however, was significantly lower in patients with unsuccessful MESA (P = 0.003). A rete testis obstruction or epididymal malfunctioning was found in 15% of patients with suspected primary OA, reflected by unsuccessful MESA despite normal inhibin-B levels and normal testicular histology.

CONCLUSIONInhibin-B cannot replace testicular biopsy as a diagnostic tool in the work-up of patients with suspected primary OA. Testicular biopsy is useful in identifying patients with spermatogenic arrest, who might have normal inhibin-B values.

Azoospermia ; blood ; diagnosis ; Biomarkers ; blood ; Biopsy ; Follicle Stimulating Hormone ; blood ; Humans ; Inhibins ; metabolism ; Luteinizing Hormone ; blood ; Male ; Microsurgery ; methods ; Paracentesis ; methods ; Predictive Value of Tests ; Retrospective Studies ; Sperm Retrieval ; Spermatozoa ; pathology ; Testis ; pathology ; Testosterone ; blood

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Modulatory effects of diallyl sulfide against testosterone- induced oxidative stress in Swiss albino mice.

Sahdeo PRASAD ; Neetu KALRA ; Yogeshwer SHUKLA

Asian Journal of Andrology.2006;8(6):719-723.

AIMTo investigate the protective effect of diallyl sulfide (DAS), a constituent of garlic, against testosterone-induced oxidative stress in male Swiss albino mice.

METHODSThe animals were given low (250 mg/animal) and high dose (500 mg/animal) of DAS in corn oil for 7 days along with testosterone (5 mg/kg body weight, i.p.). At the end of the study period, the prostate and the liver were dissected to determine various antioxidant enzyme levels (catalase, superoxide dismutase, glutathione reductase, glutathione-s-transferase) and lipid peroxidation.

RESULTSIn testosterone treated mice, depleted antioxidant enzyme level was accompanied with enhancement in lipid peroxidation in prostate and liver. DAS significantly restored the testosterone-induced antioxidant enzymes and lipid peroxidation in the both organs. These changes appear to be mediated by the antioxidant-enhancing effects of DAS.

CONCLUSIONThe results of the present study suggest that DAS is effective in exerting antioxidant effects by inhibiting testosterone-induced oxidative stress and might be helpful in preventing prostate cancer.

Allyl Compounds ; pharmacology ; Animals ; Catalase ; metabolism ; Glutathione Reductase ; metabolism ; Glutathione Transferase ; metabolism ; Lipid Peroxidation ; drug effects ; Liver ; drug effects ; Male ; Mice ; Oxidative Stress ; drug effects ; Prostate ; drug effects ; Sulfides ; pharmacology ; Superoxide Dismutase ; metabolism ; Testosterone ; antagonists & inhibitors

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