Investigation of sperm hsa-mir-145-5p and MLH1 expressions, seminal oxidative stress and sperm DNA fragmentation in varicocele.

BACKGROUND: Mechanisms by which varicocele causes infertility are not clear and few studies have reported that some miRNAs show expression alterations in men with varicocele. Recently, sperm promoter methylation of MLH1 has been shown to be higher in men diagnosed with varicocele. This study aimed to assess the potential effects of miR-145, which was determined to target MLH1 mRNA in silico on sperm quality and function in varicocele. METHODS: Sperm miR-145 and MLH1 expressions of six infertile men with varicocele (Group 1), nine idiopathic infertile men (Group 2), and nine fertile men (control group) were analyzed by quantitative PCR. Sperm DNA fragmentation was evaluated by TUNEL and the levels of seminal oxidative damage and total antioxidant capacity were analyzed by ELISA. RESULTS: Our results have shown that sperm expression of miR-145 was decreased in Group 1 compared to Group 2 (P = 0.029). MLH1 expression was significantly higher in Group 2 than the controls (P = 0.048). Total antioxidant level and sperm DNA fragmentations of Group 1 and Group 2 were decreased (P = 0.001 and P = 0.011, respectively). Total antioxidant capacity was positively correlated with sperm concentration (ρ = 0.475, P = 0.019), total sperm count (ρ = 0.427, P = 0.037), motility (ρ = 0.716, P < 0.0001) and normal morphological forms (ρ = 0.613, P = 0.001) and negatively correlated with the seminal oxidative damage (ρ=-0.829, P = 0.042) in varicocele patients. CONCLUSION: This is the first study investigating the expressions of sperm miR-145 and MLH1 in varicocele patients. Further studies are needed to clarify the potential effect of miR-145 on male fertility.

Insertional Variations of Human Endogenous Virus K6 and K11 in Normozoospermic Men.

Male infertility is a multifactorial heterogeneous reproductive disorder in which genetic, epigenetic, and environmental factors play a role in the development of disease. Recent studies have shown that retrotransposon expression alterations may be related to impairment of spermatogenesis. Therefore, in this pilot study, we aimed to investigate whether HERV-K6 and HERV-K11 insertional variations have a role in idiopathic infertility among normozoospermic men. Genomic DNA isolated from the blood samples of 41 infertile normozoospermic and 45 fertile normozoospermic men were analyzed by inter-retrotransposon polymorphism polymerase chain reaction. HERV-K6 variation rates in the infertile and the fertile group were 0-58.3% and 0-53.4%, respectively. The variation rates of HERV-K11 were 0-75.0% in infertile and 0-77.8% in fertile men. The HERV-K6 and HERV-K11 insertion rates of the fertile group were higher than the infertile group (P < 0.0001 and P = 0.007, respectively). The findings of the study suggest that HERV-K6 and HERV-K11 retrotransposon insertion show variation among individuals, and their insertions might be associated with male infertility.

Effect of partially hydrolyzed synbiotic formula milk on weight gain of late preterm and term infants-a multicenter study.

Introduction: Data on the effectiveness of hydrolyzed infant formula containing both pre- and probiotics (synbiotic formula) on the growth of infants is still scarce. This retrospective study was designed to evaluate the effect of a partially hydrolyzed synbiotic formula on growth parameters and the possible occurrence of major gastrointestinal adverse events or morbidities in infants born via cesarean section (C-section) delivery. Methods: C-section-delivered term and late preterm infants who received either partially hydrolyzed synbiotic formula, standard formula, or maternal milk and followed at seven different hospitals from five different regions of Turkey, during a 1-year period with a minimum follow-up duration of 3 months were evaluated retrospectively. All the included infants were evaluated for their growth patterns and any kind of morbidity such as diarrhea, constipation, vomiting, infection, or history of hospitalization. Results: A total of 198 infants (73 in the human milk group, 61 in the standard formula group, and 64 in the partially hydrolyzed synbiotic formula group) reached the final analysis. The groups were similar regarding their demographic and perinatal characteristics. No difference was observed between the three groups regarding gastrointestinal major side effects. Growth velocities of the infants in the human milk and partially hydrolyzed synbiotic formula groups during the first month of life were similar whereas the weight gain of infants in the standard formula group was significantly less than these two groups (p < 0.001). Growth velocities were similar among the three groups between 1st and 3rd months of age. Discussion: A partially hydrolyzed synbiotic formula provided better weight gain in late-preterm and term infants who were delivered via C-section delivery compared to the standard formula during the first month of life. This weight gain was similar to the infants receiving exclusively human milk. This difference was not observed in length and head circumference gain. No difference was observed in any of the parameters during the 1st-3rd months of age. Specially formulated partially hydrolyzed synbiotic formulas may reverse at least some of the negative impacts of C-section delivery on the infant and help to provide better growth, especially during the early periods of life.

Burden of infectious disease studies in Europe and the United Kingdom: a review of methodological design choices.

This systematic literature review aimed to provide an overview of the characteristics and methods used in studies applying the disability-adjusted life years (DALY) concept for infectious diseases within European Union (EU)/European Economic Area (EEA)/European Free Trade Association (EFTA) countries and the United Kingdom. Electronic databases and grey literature were searched for articles reporting the assessment of DALY and its components. We considered studies in which researchers performed DALY calculations using primary epidemiological data input sources. We screened 3053 studies of which 2948 were excluded and 105 studies met our inclusion criteria. Of these studies, 22 were multi-country and 83 were single-country studies, of which 46 were from the Netherlands. Food- and water-borne diseases were the most frequently studied infectious diseases. Between 2015 and 2022, the number of burden of infectious disease studies was 1.6 times higher compared to that published between 2000 and 2014. Almost all studies (97%) estimated DALYs based on the incidence- and pathogen-based approach and without social weighting functions; however, there was less methodological consensus with regards to the disability weights and life tables that were applied. The number of burden of infectious disease studies undertaken across Europe has increased over time. Development and use of guidelines will promote performing burden of infectious disease studies and facilitate comparability of the results.

Impact of Varicocele Repair on Semen Parameters in Infertile Men: A Systematic Review and Meta-Analysis.

PURPOSE: Despite the significant role of varicocele in the pathogenesis of male infertility, the impact of varicocele repair (VR) on conventional semen parameters remains controversial. Only a few systematic reviews and meta-analyses (SRMAs) have evaluated the impact of VR on sperm concentration, total motility, and progressive motility, mostly using a before-after analytic approach. No SRMA to date has evaluated the change in conventional semen parameters after VR compared to untreated controls. This study aimed to evaluate the effect of VR on conventional semen parameters in infertile patients with clinical varicocele compared to untreated controls. MATERIALS AND METHODS: A literature search was performed using Scopus, PubMed, Embase, and Cochrane databases following the Population Intervention Comparison Outcome (PICOS) model (Population: infertile patients with clinical varicocele; Intervention: VR [any technique]; Comparison: infertile patients with clinical varicocele that were untreated; Outcome: sperm concentration, sperm total count, progressive sperm motility, total sperm motility, sperm morphology, and semen volume; Study type: randomized controlled trials and observational studies). RESULTS: A total of 1,632 abstracts were initially assessed for eligibility. Sixteen studies were finally included with a total of 2,420 infertile men with clinical varicocele (1,424 patients treated with VR vs. 996 untreated controls). The analysis showed significantly improved post-operative semen parameters in patients compared to controls with regards to sperm concentration (standardized mean difference [SMD] 1.739; 95% CI 1.129 to 2.349; p<0.001; I²=97.6%), total sperm count (SMD 1.894; 95% CI 0.566 to 3.222; p<0.05; I²=97.8%), progressive sperm motility (SMD 3.301; 95% CI 2.164 to 4.437; p<0.01; I²=98.5%), total sperm motility (SMD 0.887; 95% CI 0.036 to 1.738; p=0.04; I²=97.3%) and normal sperm morphology (SMD 1.673; 95% CI 0.876 to 2.470; p<0.05; I²=98.5%). All the outcomes showed a high inter-study heterogeneity, but the sensitivity analysis showed that no study was sensitive enough to change these results. Publication bias was present only in the analysis of the sperm concentration and progressive motility. No significant difference was found for the semen volume (SMD 0.313; 95% CI -0.242 to 0.868; I²=89.7%). CONCLUSIONS: This study provides a high level of evidence in favor of a positive effect of VR to improve conventional semen parameters in infertile men with clinical varicocele. To the best of our knowledge, this is the first SRMA to compare changes in conventional semen parameters after VR with changes in parameters of a control group over the same period. This is in contrast to other SRMAs which have compared semen parameters before and after VR, without reference to a control group. Our findings strengthen the available evidence and have a potential to upgrade professional societies' practice recommendations favoring VR to improve conventional semen parameters in infertile men.

The Interrelationship Between FYN and miR-128/193a-5p/494 in Imatinib Resistance in Prostate Cancer.

BACKGROUND: C-KIT is a receptor tyrosine kinase with oncogenic properties overexpressed in PCa cases. Through the use of an alternative promoter, a truncated c-KIT protein (tr-KIT) of 30-50 kDa is generated, lacking the extracellular and transmembrane domain. Tr-KIT promotes the formation of a multi-molecular complex composed of Fyn, Plcγ1, and Sam68. Imatinib blocks the activity of full-length c-KIT but has no effect on tr-KIT. LNCaP is the human PCa cell line that shows tr-KIT overexpression and PC3 does not show tr-KIT overexpression. miR-128/193a- 5p/494 are miRNAs targeting FYN, PLCγ1, and SAM68 combinatorially. The study's question is: can miR-128/193a- 5p/494 be related to imatinib resistance in PCa? METHODS: LNCaP and PC3 cells were treated with imatinib in IC50 doses. Before and after imatinib administration, RNA was isolated and cDNA conversion was performed. By qPCR analysis, expression changes of tr-KIT specific pathway elements and miR-128/193a-5p/494 were analyzed before and after imatinib administration. RESULTS: After imatinib administration, miR-128/193a-5p/494 were significantly overexpressed in LNCaP cells while downregulated significantly in PC3 cells (p<0.05). Also, FYN was upregulated in LNCaP cells (p<0.05) but there was no change in PC3 after imatinib administration. CONCLUSION: Especially upregulation of FYN may sponge miR128/193a-5p/494 and downregulate their transcriptional activity in LNCaP cells having tr-KIT activity. So, miR-128/193a-5p/494 may have a critical role in imatinib resistance via a tr-KIT pathway.

Clinical, cytogenomic, and molecular characterization of isodicentric Y-chromosome and prediction of testicular sperm retrieval outcomes in azoospermic and severe oligozoospermic infertile men.

PURPOSE: Sex chromosome abnormalities are associated with male infertility. The aim of this study was to characterize the clinical, cytogenetic, and molecular findings of 12 infertile men with isodicentric Y-chromosome [idic(Y)] abnormalities diagnosed over a period of 13 years. MATERIALS AND METHODS: Chromosomal analyses of peripheral blood samples were done using standard procedures. Fluorescence in situ hybridization (FISH) analysis was performed on metaphase spreads of the patients. Multiplex polymerase chain reaction (PCR) using several sequence-tagged site (STS) primer sets within the long arm of Y-chromosome was used to detect AZF deletions.The breakpoints and copy number variations (CNV) were identified by array comparative genomic hybridization analysis (aCGH) analysis.The short-stature homeobox (SHOX) gene deletions were verified using multiplex ligation-dependent probe amplification (MLPA) analysis. RESULTS: Twelve infertile men were diagnosed cytogenetically with idic(Y). The karyotypes of two of the patients were non-mosaic, and the remaining karyotypes showed various degrees of mosaicism. SHOX gene deletion was found in two of the four patients with short stature, and the remaining two patients had shown a 45,X dominant cell line (33.3%). The most common breakpoints for idic(Yq) and idic(Yp) were found to be in Yq11.222 and Yp11.32, respectively. Semen analysis of ten patients (83.3%) demonstrated azoospermia, and the remaining two patients (16.7%) showed severe oligoasthenoteratozoospermia (OAT). In total, 33% (4/12) of idic(Y) patients with or without microsurgical testicular sperm extraction (microTESE) had sperm retrieval. CONCLUSIONS: Twelve patients with idic(Y) and different breakpoints of Y-chromosome were characterized using multiple detection strategies. Sperm retrieval outcomes of patients either with idic(Yp) or idic(Yq) showed the possibility to find sperm by microTESE.

In silico analysis of microRNA genes in azoospermia factor Y-chromosome microdeletions.

PURPOSE: Microdeletion on Y-chromosome is a well-known genetic cause of infertility in azoospermic and oligozoospermic men. RNA transcripts possess microRNA (miRNA) response elements (MRE) that may interact with competing endogenous RNAs (ceRNA), thus repressing their activity. MiRNAs originally targeting transcripts of genes deleted in the Y-chromosome azoospermia factor (AZF) region are expected to be oriented to binding sites of new targets. We investigated miRNAs targeting genes of each AZF locus (AZFa, AZFb, AZFb-c, and AZFc) to determine their corresponding ceRNA using in silico analysis. METHODS: The miRNAs targeting most of the genes deleted in each AZF locus were identified using the miRWalk database. Twelve miRNAs exhibiting potential ceRNA activity were identified and analyzed using the ComiR database. Detected ceRNAs for each AZF locus were processed in the GeneMANIA database for interaction prediction, and the most probably interacted genes were identified. RESULTS: RPPA2, TMED3, STX7 and ATRX, GOGLB1, KMT2C genes were found potential ceRNAs for the AZFa and AZFb regions, respectively. Furthermore, CNB5, KCNC4, NDUFS1 and TROBP, HEMK1, and ORAI2 genes were the potential ceRNAs for the partially AZFb-c-overlapped region and AZFc regions, respectively. CONCLUSION: Our findings suggest that AZF loci deletion may change post-transcriptional regulation of gene expression through miRNA competition.

Follicle-stimulating hormone beta subunit and receptor variations in infertile men in Central Black Sea Region of Turkey.

Genetic variants affecting the interaction of FSH-FSHR may negatively affect the male reproductive potential. The aim of this case-control study was to evaluate FSHB c.-211G>T and FSHR c.2039A>G variants in a cohort of infertile men from Central Black Sea Region in Turkey. One hundred and nine infertile men and 50 proven fertile controls were enrolled in the study. Genotyping was assessed by RFLP. The genotype frequencies of FSHB -211G>T and FSHR 2039A>G showed significant variation between infertile and fertile groups (χ2 , p = 0.046, GG vs. GT+TT, and p = 0.008, AA vs. AG+GG). FSHB -211GG was found to be higher in patients with OAT compared to fertile controls (82.3% vs. 64.0%, χ2 , p = 0.028). The distribution of FSHR 2039A>G alleles was different between infertile and fertile men (χ2 , p = 0.005, total infertile vs. fertile groups, p = 0.019, OAT vs. NOA vs. fertile groups). Further analysis showed that the frequencies of FSHR 2039AA wild-type genotype were higher in the oligoasthenoteratozoospermic and non-obstructive azoospermic groups compared with the controls (χ2 , 39.3% vs. 17.0%, p = 0.012, and 37.5% vs. 17.0%, p = 0.025 respectively). Our results showed wild-types of FSHB -211G>T and FSHR 2039A>G variants may cause susceptibility to male infertility in the Central Black Sea Region of Turkey.

Polymorphisms of androgens-related genes and idiopathic male infertility in Turkish men.

Androgens, testosterone and dihydrotestosterone (DHT) are endocrine regulators of spermatogenesis and act via androgen receptor (AR). The aim of this study was to investigate the association(s) of AR (CAG repeat length), SRD5A2 (rs523349, V89L) and TNF-α (rs1800629, -308G/A) polymorphisms with idiopathic male infertility in Turkish men. This case-control study consisted of 312 men with idiopathic infertility and 113 fertile men. Polyacrylamide gel electrophoresis (PAGE) or PCR-restriction fragment length polymorphism methods were used for genotyping. The mean AR CAG repeat length was significantly longer in infertile men than in fertile men (p = 0.015). However, there was no significant association between the SRD5A2 genotypes (VV, VL and LL) and the risk of infertility (p = 0.516). The genotype frequency and allele distribution of TNF-α -308G/A polymorphism (GG, GA, AA genotypes and G, A alleles) were not associated with male infertility (p = 0.779 and p = 0.743 respectively). AR CAG repeat expansion might be one of the risk factors for idiopathic male infertility in Turkish men. Further studies investigating the association of male infertility with AR CAG, V89L and -308G/A polymorphisms are warranted to understand the possible associations among them.

Association among sperm chromatin condensation, sperm DNA fragmentation and 8-OHdG in seminal plasma and semen parameters in infertile men with oligoasthenoteratozoospermia.

The present study aimed to investigate the clinical role of standard sperm diagnosis parameters (sperm concentration, motility, morphology) as well as aniline blue staining of histones, 8-OHdG, TUNEL assay were performed on semen samples in infertile men with oligoasthenoteratozoospermia (OAT). Thirty-two infertile and ten proven fertile men were included in the study. Chromatin condensation sperm in infertile men was significantly lower compared to the fertile men (p < 0.0001). Age, sperm concentration, morphology and motility were significantly negatively correlated with chromatin condensation (p < 0.05). However, no significant correlations among the chromatin condensation, SDF and sperm DNA damage were detected in terms of 8-OHdG concentration.

Semiquantitative promoter methylation of MLH1 and MSH2 genes and their impact on sperm DNA fragmentation and chromatin condensation in infertile men.

To investigate the semiquantitative methylation alterations of MLH1 and MSH2 and the possible association among methylation of MLH1 and MSH2, sperm DNA fragmentation and sperm chromatin condensation in idiopathic oligoasthenoteratozoospermic men. Seventy-five idiopathic infertile men and 52 fertile and/or normozoospermic men were included in the study. SDF was analysed using the TUNEL assay in semen samples of 100 men. Promoter methylation of MLH1 and MSH2 genes was assessed by semiquantitative methylight analysis in semen samples of 39 and 40 men respectively. Sperm chromatin condensation was evaluated using aniline blue staining in 114 men. MLH1 promoter methylation was positively correlated with the percentage of aniline blue positive spermatozoa (r = 0.401, p = 0.0188). On the other hand, MSH2 promoter methylation was negatively correlated with sperm concentration and total sperm count (r = -0.421, p = 0.0068 and r = 0.4408, p = 0.009 respectively). The percentage of aniline blue positive spermatozoa in the control group was significantly lower than in the OAT group (p < 0.0001) and negatively correlated with total sperm count (r = -0.683, p < 0.0001), progressive sperm motility (r = -0.628, p < 0.0001), total motility (r = -0.639, p < 0.0001) and normal morphology (r = -0.668, p < 0.0001). Promoter methylation profile of MLH1 and MSH2 genes may play role on sperm DNA packaging and conventional semen parameters respectively.

Role of genetics and epigenetics in male infertility.

Male infertility is a complex condition with a strong genetic and epigenetic background. This review discusses the importance of genetic and epigenetic factors in the pathophysiology of male infertility. The interplay between thousands of genes, the epigenetic control of gene expression, and environmental and lifestyle factors, which influence genetic and epigenetic variants, determines the resulting male infertility phenotype. Currently, karyotyping, Y-chromosome microdeletion screening and CFTR gene mutation tests are routinely performed to investigate a possible genetic aetiology in patients with azoospermia and severe oligozoospermia. However, current testing is limited in its ability to identify a variety of genetic and epigenetic conditions that might be implicated in both idiopathic and unexplained infertility. Several epimutations of imprinting genes and developmental genes have been postulated to be candidate markers for male infertility. As such, development of novel diagnostic panels is essential to change the current landscape with regard to prevention, diagnosis and management. Understanding the underlying genetic mechanisms related to the pathophysiology of male infertility, and the impact of environmental exposures and lifestyle factors on gene expression might aid clinicians in developing individualised treatment strategies.

Association of XRCC1 and ERCC2 promoters' methylation with chromatin condensation and sperm DNA fragmentation in idiopathic oligoasthenoteratozoospermic men.

The aim of the study was to investigate whether the promoter methylation of XRCC1 and ERCC2 genes is associated with sperm DNA fragmentation and chromatin condensation in idiopathic oligoasthenoteratozoospermic men. This study involved 77 infertile men with idiopathic oligoasthenoteratozoospermia and 51 normozoospermic controls. The methylight method, TUNEL assay and aniline blue staining were used for the evaluation of XRCC1 and ERCC2 genes' methylation, SDF and sperm chromatin condensation, respectively. SDF (p = .004) and XRCC1 methylation (p = .0056) were found to be significantly higher in men with idiopathic OAT than in the controls, while mature spermatozoa frequency was higher in controls as compared to infertile men (p < .0001). No significant association was found between SDF and methylation of XRCC1 and ERCC2 genes (p = .9277 and p = .8257, respectively). However, compared to the cut-off point obtained by receiver operating characteristic analysis, a significant association was found between SDF and XRCC1 methylation, positive and negative methylation groups, generated according to the cut-off value for XRCC1. XRCC1 methylation was found to have a significant effect on chromatin condensation (p = .0017). No significant difference was detected among ERCC2 methylation, male infertility and SDF. In conclusion, XRCC1 methylation may have a role in sperm chromatin condensation and idiopathic OAT.

Methylation patterns of methylenetetrahydrofolate reductase gene promoter in infertile males.

Errors of folate/homocysteine pathways which are critical for transferring methyl groups have been suggested to affect male fertility. We aimed to evaluate the methylation patterns of the promoter of methylenetetrahydrofolate reductase (MTHFR) gene in infertile males and to investigate the association between MTHFR promoter methylation and success of sperm retrieval. Thirty-five nonobstructive azoospermic and 46 severe oligozoospermic patients constituted the study group and were compared with 49 fertile and/or normozoospermic men. The methylation status was analysed by methylation-specific polymerase chain reaction. MTHFR promoter methylation was detected in infertile men with NOA and SO in the ratio of 48.6% and 58.7%, respectively. Methylation was also observed in 51% of controls. MTHFR promoter was methylated in 65% of men with viable spermatozoon during TESE. No association was found regarding to the profile of MTHFR promoter methylation between both NOA and SO patients and controls (p = .621). There was no relation between the methylation status of MTHFR promoter and low motility and poor morphology (p = .682 and p = .413, respectively). No association was found between MTHFR promoter methylation and presence of viable spermatozoa (p = .382). Our data indicate that the promoter methylation of MTHFR gene may not be associated with male infertility.

Multiscale analysis of SRY-positive 46,XX testicular disorder of sex development: Presentation of nine cases.

46,XX testicular disorder of sex development (46,XX TDSD) is a relatively rare condition characterised by the presence of testicular tissue with 46,XX karyotype. The present study aims to reveal the phenotype to genotype correlation in a series of sex-determining region Y (SRY)-positive 46,XX TDSD cases. We present the clinical findings, hormone profiles and genetic test results of six patients with SRY-positive 46,XX TDSD and give the details and follow-up findings of our three of previously published patients. All patients presented common characteristics such as azoospermia, hypergonadotropic hypogonadism and an SRY gene translocated on the terminal part of the short arm of one of the X chromosomes. Mean ± standard deviation (SD) height of the patients was 164.78 ± 8.0 cm. Five patients had decreased secondary sexual characteristics, and three patients had gynaecomastia with varying degrees. Five of the seven patients revealed a translocation between protein kinase X (PRKX) and inverted protein kinase Y (PRKY) genes, and the remaining two patients showed a translocation between the pseudoautosomal region 1 (PAR1) of X chromosome and the differential region of Y chromosome. X chromosome inactivation (XCI) analysis results demonstrated random and skewed XCI in 5 cases and 1 case, respectively. In brief, we delineate the phenotypic spectrum of patients with SRY-positive 46,XX TDSD and the underlying mechanisms of Xp;Yp translocations.

Association of Abl interactor 2, ABI2, with platelet/lymphocyte ratio in patients with renal cell carcinoma: A pilot study.

There are many unknown aspects of the pathogenesis of renal cell carcinoma (RCC). The aim of the current study was to define new RCC-related genes and measure their associations with RCC and clinical parameters, especially platelet/lymphocyte ratio which may be an independent predictor of prognosis in patients with RCC and other forms of cancer. Via in silico analysis upon RCC-specific deleted genes in chromosome 3, four possible ceRNAs (ATXN3, ABI2, GOLGB1 and SMAD2) were identified. Then, the expression levels of these genes in tumour and adjacent healthy kidney tissues of 19 RCC patients were determined by real-time PCR. ATXN3 and GOLGB1 gene expression levels increased but ABI2 gene expression level decreased in tumour kidney tissues when compared to normal ones. ATXN3, ABI2 and GOLGB1 gene expression levels were significantly higher in Fuhrman grade 4 than other grades (P < .001). ABI2 gene expression levels were significantly associated with higher platelet/lymphocyte ratio of the patients with RCC (P < .05). ATXN3, ABI2 and GOLGB1 may predict higher RCC grades. Also, ABI2 may regulate platelet/lymphocyte ratio which may be an independent predictor of RCC and other forms of cancer.

Microtubular Dysfunction and Male Infertility.

Microtubules are the prime component of the cytoskeleton along with microfilaments. Being vital for organelle transport and cellular divisions during spermatogenesis and sperm motility process, microtubules ascertain functional capacity of sperm. Also, microtubule based structures such as axoneme and manchette are crucial for sperm head and tail formation. This review (a) presents a concise, yet detailed structural overview of the microtubules, (b) analyses the role of microtubule structures in various male reproductive functions, and (c) presents the association of microtubular dysfunctions with male infertility. Considering the immense importance of microtubule structures in the formation and maintenance of physiological functions of sperm cells, this review serves as a scientific trigger in stimulating further male infertility research in this direction.

SNP's in xenobiotic metabolism and male infertility.

1. Glutathione S-transferases (GST) and cytochrome P450s (CYPs) are xenobiotic metabolizing enzymes participating in the protection of cell. The present study aimed to investigate the relationship between polymorphisms of glutathione S-transferase M1 (GSTM1) null, glutathione S-transferase T1 (GSTT1) null, glutathione S-transferase P1 (GSTP1) Ile105Val, cytochrome P450 1A2 (CYP1A2) 734 C→A, cytochrome P450 2D6 (CYP2D6) 1934 G→A and male infertility.2. A total of 306 azoospermic or oligozoospermic infertile men and 129 normozoospermic or fertile controls were enrolled in the study. Multiplex polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism methods were used for genotyping. There was a significant relationship between male infertility and CYP2D6 GG genotype (p < 0.001). CYP1A2 AA genotype was slightly higher in the infertile group (p = 0.056).3. There was no association between GSTT1 null polymorphisms and male infertility (p = 0.068), GSTM1 null (p = 0.843) and GSTP1 Ile105Val (p = 0.192) genes. GSTM1 null genotype frequency was higher in azoospermic men (p = 0.009). Men carrying CYP1A2 AA genotype had higher risk of infertility risk (OR = 3.14; %95 CI = 1.16-8.54) in the smoker group.4. Our results demonstrated that polymorphisms of CYP2D6 and CYP1A2 may play a role in idiopathic male infertility in our sample population.