Top PDF MicroRNA and Male Infertility: A Potential for Diagnosis

MicroRNA and Male Infertility: A Potential for Diagnosis

MicroRNA and Male Infertility: A Potential for Diagnosis

MicroRNAs (miRNAs) are small non-coding single stranded RNA molecules that are physiologically produced in eukaryotic cells to regulate or mostly down-regulate genes by pairing with their complementary base-sequence in related mRNA mol- ecules in the cytoplasm. It has been reported that other than its function in many physiological cell processes, dysregulation of miRNAs plays a role in the develop- ment of many diseases. In this short review, the association between miRNAs and some male reproductive disorders is surveyed. Male factor Infertility is a devas- tating problem from which a notable percentage of couples suffer. However, the molecular mechanism of many infertility disorders has not been clearly elucidated. Since miRNAs have an important role in numerous biological cell processes and cellular dysfunctions, it is of interest to review the related literature on the role of miRNAs in the male reproductive organs. Aberrant expression of specific miRNAs is associated with certain male reproductive dysfunctions. For this reason, assess- ment of expression of such miRNAs may serve as a suitable molecular biomarker for diagnosis of those male infertility disorders. The presence of a single nucleotide polymorphism (SNP) at the miRNAs’ binding site in its targeted mRNA has been reported to have an association with idiopathic male infertility. Also, a relation with male infertility has been shown with SNP in the genes of the factors necessary for miRNA biogenesis. Therefore, focusing on the role of miRNAs in male reproduc- tive disorders can further elucidate the molecular mechanisms of male infertility and generate the potential for locating efficient biomarkers and therapeutic agents for these disorders.
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MicroRNA-92a as a potential biomarker in diagnosis of colorectal cancer: a systematic review and meta-analysis.

MicroRNA-92a as a potential biomarker in diagnosis of colorectal cancer: a systematic review and meta-analysis.

All the studies were carefully decided by two investigators (X.Y and Z.Y.Z) independently based on titles and abstracts, and then found full text for any potential eligibility. Any disagreement was resolved by fully discussion to consensus. Furthermore, if necessary, we turned to the original authors for missing data. Each inclusion article must meet to following criteria: (1) The diagnosis of CRC was based on colonoscopy or histological examination; (2) The matched control individuals were included with a recent negative result of colonoscopy and without a personal history of any types of cancer; (3) All blood samples were collected prior to colonoscopy and without any treatment; (4) The researchers assessed the miR-92a in blood sample alone; (5) The studies should contain the data of sensitivity, specificity (or the possibility of deriving such values from the data), and a clear cut- off value; (6) Only the study with more than 20 cases and matched controls were included. All the studies were excluded if they had any of the following items: (1) Duplicate publications; (2) Letters, editorials, meeting abstracts, case reports and reviews; (3) Unqualified patients and control subjects, as well as their blood samples; (4) Insufficient data. If the same author reported their results acquired from the overlapping population or multiple published data in the different works, only the nearest or the most complete report was included.
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POTENTIAL IMMUNOLOGICAL MARKERS FOR DIAGNOSIS AND THERAPEUTIC ASSESSMENT OF TOXOCARIASIS

POTENTIAL IMMUNOLOGICAL MARKERS FOR DIAGNOSIS AND THERAPEUTIC ASSESSMENT OF TOXOCARIASIS

mm wide, blocked for 30 min at 37 °C with 1% skim milk (Molico, Nestle, Araçatuba, São Paulo, Brazil) in phosphate-buffered saline containing 0.05% Tween 20 (PBS-T). The serum samples were diluted 1/100 for IgG-IB and 1/20 for both IgA and IgE-IB with 1% skim milk in PBS-T, and strips were incubated for 18 h at 4 °C. All serum samples had been pre-absorbed with AWE (25 µg/mL) in PBS-T for 30 min at 37 °C. For IgE-IB, serum samples had been also pre-absorbed with RF-absorbent (v/v) (Dade Behring, Marburg, Germany) for 18 h at 4 °C, in order to enhance the detection of IgE antibodies. After washing, the strips were incubated for two h at 37 °C with peroxidase conjugates diluted in 1% skim milk in PBS-T as follows: 1/1000 dilution for anti-human IgG (Biolab Diagnostic, Rio de Janeiro, Brazil); 1/200 dilution for anti-human IgA (Dako, Denmark); and 1/160 dilution of anti-human IgE (Sigma Chemical Co, St Louis, MO, USA). Then the strips were washed and treated with 4-chloro-α-naphthol (0.05% in methanol) and 0.8 µL/mL H 2 O 2 30%. After 15 min the reaction was interrupted with distilled water.
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Experiencing Male Infertility

Experiencing Male Infertility

Within the literature reviewed here, men’s emotions and emotional responses to infertility are conceptualized via the notion of “emotional distress.” For example, some authors suggest that women suffer more emotional distress when diagnosed infertile than men do, encapsulated by the idea that “while women were often devastated by infertility, men were merely disappointed” (Lloyd, 1996, p. 434). Others (for example, Peronace, Bovin, & Schmidt, 2007), however, sug- gest that men experience similar levels of distress as women in relation to infertility. Research has then perhaps focused more on the gendered understanding of “who is more dis- tressed” (Greil et al., 2010) rather than the specific nature of the distress that men may feel in terms of a diagnosis of infertility. It is also argued that the nature of women’s dis- tress is perhaps overstated by the focus of infertility research on women and the framing of questions toward female expe- riences (Jordan & Revenson, 1999). The suggestion that “since men will speak less about personal things, the men with disturbed fertility mostly kept their emotional distress to themselves” (Kowalcek et al., 2001, p. 1136) then creates perceived challenges for research around male infertility, particularly in relation to how men feel and capturing the nature of any distress they feel. The idea that men do not speak about emotional distress is however generalized at best, and could be argued to be perhaps grounded in assump- tions rather than evidence. Work such as Malik and Coulson’s (2008) exploration of online forum postings by men perhaps offers an interesting approach to gain access to men’s “insider” accounts and raises questions about how men may talk about infertility and in what settings. This is, however, quite an isolated piece of work, and the use of the Internet to explore infertility has much potential here. An article in the Telegraph (Cooper, 2014) interviewed a male blogger, who uses his blog to discuss his infertility journey; blogs may therefore be another route through which Internet-mediated research could be conducted around the experience of men and infertility. Other recent work shows the value of online sources for research, with work examining men’s accounts around diverse topics, from wearing make-up to being depressed (Gough, 2015; Hall, Gough, & Seymour-Smith, 2013).
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OPERATIONS NECESSARY FOR THE DIAGNOSIS ANALYSIS OF THE ORGANIZATION

OPERATIONS NECESSARY FOR THE DIAGNOSIS ANALYSIS OF THE ORGANIZATION

ABSTRACT: The diagnosis analysis is as important as is necessary for any profit or non-profit organization, it shows the situation of the organization, helps to prevent the risks, threats and future forecast. The diagnosis analysis must present: the general situation, financial situation, human and managerial potential, technical and technological potential of the organization. Once known these aspects important for the organization, the decision or decisions can be made being aware of it and in real time. The diagnosis analysis is a procedure which is achieved in a relatively short period of time and offers solutions with global character, formulates an action program which will include detailed analysis. The high degree of complexity of the analysis needs a multidisciplinary training which can establish the method, to collect and process the data and to offer the solutions, for which this can be made by specialized companies or by specialized staff from organization self-analysis.
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Diagnostic Potential of Circulating MicroRNA-21 in Hepatocellular Carcinoma.

Diagnostic Potential of Circulating MicroRNA-21 in Hepatocellular Carcinoma.

potentially may be useful to limit HCC growth and metastasis. Further work is warranted to evaluate the role of miR-21 and the identified downstream targets and to develop therapeutic strategies targeting miR-21 in vivo. The ability to therapeutically manipulate miRNA expression is feasible, and recent proof-of-concept studies have shown that miRNA antagonists targeted to the liver can modulate expression of downstream genes (12). We come to an important clue, when doing the experiment on whole blood taken on EDETA. Assessment of the Circulating MiRNA-21 level Expression in the studied groups (HCC, HCV & Control), the results and findings were approximately identical to those done on tissue by variable techniques. And since this experiment was delivered in National Liver Institute on Egyptian people, it is not a role to give the same findings in other countries or circumstances. However, the accuracy of the obtained results compared to tissue samples could be very beneficial in avoiding invasive techniques like biopsies to obtain tissue samples. Another very important diagnostic value is the relation of MiRNA-21 and focal lesion size in HCC, Table (3) where it shows a highly significant correlation between MiRNA-21 and focal lesion size largest diameter. Which could be implemented in early diagnosis of HCC. This finding agreed with Qibin Liao et al., 2015(20) who confirmed that as a potential diagnostic biomarker for HCC, circulating miR-21 possesses several unique advantages. First, serum or plasma microRNA is characterized by minimal invasion and convenience compared with histopathological examination. Second, serum microRNA expression levels are stable and reproducible (21); Third, plasma miR-21 level cannot be influenced by both cirrhosis and viral
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Association study of folate-related enzymes (MTHFR, MTR, MTRR) genetic variants with non-obstructive male infertility in a Polish population

Association study of folate-related enzymes (MTHFR, MTR, MTRR) genetic variants with non-obstructive male infertility in a Polish population

No significant impact of the studied polymorphisms on male infertility was revealed in the present study. The original concept of the impact of MTHFR variants on male reproduction and initial positive association of the thermo- labile 677T variant with infertility came from the German study of Bezold et al. (2001), who reported significant overrepresentation of TT homozygotes among male pa- tients seeking fertility evaluation compared with control group (18.8 vs. 9.5%). This preliminary report, without de- tailed characterization of neither male infertility nor control subjects, has been subsequently followed by several studies in Caucasian populations, i.e. Dutch (Ebisch et al., 2003), Italian (Stuppia et al., 2003), Swedish (Murphy et al., 2011), and Spanish (Camprubi et al., 2013). Contrary to the original report, the results of all aforementioned studies were negative. It should be noted that most of them simply lacked sufficient power to verify the existence of the inves- tigated association, as numbers of participants were low (Table 2). Nonetheless negative association results were accompanied by findings on a potential relationship of MTHFR genotype and sperm counts, but only in some stud- ies. Ravel et al. (2009) did not find any association between MTHFR (677C > T, 1298A > C and 215GA - rs2066472) genetic variants and sperm counts in French infertile men, which was later confirmed by Montjean et al. (2011) in a larger cohort of mixed ethnicity. Similarly, none of the ge- notypes was associated with neither standard seminogram parameters nor presence of sperm DNA hypomethylation (Camprubi et al., 2013). Finally, in the recent report from an East European population in Russia, Weiner et al. (2014) have observed the association of MTHFR genotype with azooospermia, but found no general impact of MTHFR 677C > T and MTHFR 1298A > C polymorphisms on male infertility. Summarizing the observations from Caucasian studies, including the present Polish one, it seems that MTHFR 677C > T and MTHFR 1298A > C polymorphisms are not associated with male infertility.
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Clinics  vol.66 número4

Clinics vol.66 número4

seminal parameters of an individual actually represent the result of influential biological, physical and occupational factors that have been present within the two months prior to semen collection. The hormonal control of sperm production involves the hypothalamus (gonadotropin releasing hormone [GnRH]), the anterior pituitary gland (gonadotropins – follicle-stimulating hormone [FSH] and luteinizing hormone [LH]), and the testicles (testosterone and inhibin). The storage and maturation of spermatozoa occur in the epididymis. The maturation process is, however, only fully completed within the female reproduc- tive tract. The duration of spermatozoa transit throughout the epididymis is approximately 12 days. Both seminal vesicles and the vas deferens have a common embryologic origin. As such, when congenital bilateral absence of vas deferens (CBAVD) is diagnosed, it is often associated with seminal vesicle hypoplasia/agenesia. This aspect is impor- tant in terms of the differential diagnosis of azoospermia. In most CBAVD cases, the semen volume is reduced and the semen does not contain fructose. Under normal conditions, spermatozoa are stored in the epididymides. At the time of ejaculation, ductal and epididymal muscle contractions under sympathetic stimulation conduct the spermatozoa towards the prostatic urethra where they join fluids excreted by both the prostate and seminal vesicles to form semen. Periurethral muscle contraction is responsible for expelling the semen out of the urethra. Interference in any of these steps may lead to male infertility, and the pathophy- siological mechanism involved is dependent on which organ or regulatory system is afflicted.
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A genetic study of male infertility centered in semen hyperviscosity and asthenozoospermia phenotypes

A genetic study of male infertility centered in semen hyperviscosity and asthenozoospermia phenotypes

In a brief overview of the used methodology, this survey was carried out by paired-end sequencing on an Illumina HiSeq Platform (Macrogen, Inc) with an average coverage of 30x, which comprised all known coding regions as well as 5’- and 3’-untranslated regions (UTRs). Then, sequenced reads were aligned against the human reference sequence (hg19) and variants annotated using an established pipeline comprising several standard tools (BWA, SAMtools, GATK, Picard and VCFtools). Next, identified variants were compared with 1000 Genomes data for the Iberian population (IBS), which used as a control sample and as a source to sort SNVs according to their minor allele frequency (MAF). A 0.05 frequency was used to define common (MAF≥0.05) and low-frequency (MAF <0.05) variants. In a first analysis of common SNVs, two regions stood out by their potential significant associations with both SHV and AST phenotypes (Figure 6). Specifically, the two most promising male infertility candidates were the oxidative stress-induced growth inhibitor 1 (OSGIN1) gene and HLA-DRB5 locus.
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Perinatal outcomes by mode of assisted conception and sub-fertility in an Australian data linkage cohort.

Perinatal outcomes by mode of assisted conception and sub-fertility in an Australian data linkage cohort.

tion was significantly protective against birth defects in ICSI, but not IVF, where the risks in fresh cycles were relatively low [13]. In the present study, cryopreservation reduced risk magnitudes for stillbirth, small birth size and early delivery outcomes for IVF, and eliminated those risks for ICSI. It is uncertain why cryopreserva- tion may be more beneficial in ICSI than IVF treatment. However, this may reflect differences in the characteristics of patients accessing these treatments, as ICSI was generally used for male infertility and IVF for female infertility. Hence, IVF cycles may have a higher proportion of female-factor only patients where the selection effect of a freeze-thaw cycle may be diluted. Alternatively, there may be an ICSI-specific effect on growth patterns. We observed that frozen-embryo transfer was associated with increased likelihood of large size for gestational age among singletons born after ICSI. This association has been reported previously, albeit in studies that pooled IVF and ICSI cycles [31,32]. However, caution is warranted in the interpretation of findings for the ICSI with frozen-embryo cycles group as the number of patients treated in this way is small, and data are pooled for singletons and twins for some outcomes. Further research is required to understand the cause of these possible risk differentials and their impact on longer term health outcomes, particularly with regard to the potential for perturbation of the fetal epigenome [33].
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24 ], which is also supported by the fact that, in the 2002 Volkel

24 ], which is also supported by the fact that, in the 2002 Volkel

correlated with decreased semen quality and male infertility, for which induction of germ cell apoptosis is considered a primary contributing factor [101]. BPA-induced apoptosis was previously observed in human trophoblastic cells in vitro for a concentration of 1 µM [102] as well as in rat ovarian cells in vivo after prolonged exposure [103], indicating a potential negative role in reproductive function. Occupational exposure to BPA resulted in increased urine BPA levels significantly associated with decreased sperm concentration, total sperm count, vitality and motility [59]. Liu and co-workers demonstrated that the presence of elevated BPA urinary levels is also associated with alterations of relevant laboratory parameters that may contribute to male infertility, namely prolactin, estradiol and sex hormone-binding globulin (SHBG) [62]. Increased mean serum BPA concentration has also been associated with decreased mean androstenedione (AD) level (0.18 ng/mL, 95 % CI − 0.22 to − 0.13) and increased mean serum sex hormone-binding globulin (SHBG) level (2.79 nmol/L, 95% CI 2.11–3.46) in male workers from exposed to epoxy resin factories [77]. Moreover, in male exposed workers sperm methylation level of long interspersed nucleotide elements (LINE-1), a marker of global genome methylation status, was significantly decreased when compared to unexposed workers [61]. Interestingly, previous reports have demonstrated that BPA exposure in the range detected both in environmental and occupational levels induces transcriptional deregulation of LINE1 in cellular models (HUVEC and HT29) associated with global transcription deregulation [104]. Moreover, the activation of mitogen-activated protein kinases (MAPK) are believed to be involved in the damaging effects of BPA on testicular function associated with disruption of the Sertoli cell tight junction (TJ)-barrier function at the blood-testis barrier. Therefore the use of specific inhibitors against MAPK are being considered a possibility to "manage" the negative health effects and/or "protect" occupationally exposed individuals [105].
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Partial deletion of chromosome 8 β-defensin cluster confers sperm dysfunction and infertility in male mice.

Partial deletion of chromosome 8 β-defensin cluster confers sperm dysfunction and infertility in male mice.

sequence of the mouse genome (GRC m39) reveals that the region we have deleted specifically contains only these nine b-defensin genes and no other annotated feature expressed in the male reproductive tract are found. However, we do not know which of the deleted gene(s) in the cluster are responsible for the unique fertility phenotype. It is suggested that epididymal maturation of sperm cells occurs most likely in the caput or corpus region of the epididymis rather than the cauda [9]. Of the 9 genes, only Defb15, Defb35 and Defb13 are strongly expressed in these regions with the others being expressed predominantly in the cauda [10]. We have evidence from mass spectrometry analyses that Defb2, Defb11 and Defb15 are present on isolated wild-type cauda sperm (data not shown), but have not detected the other peptides. Rat Defb15 binds the acrosomal region of caput sperm, and incomplete knockdown results in rats with reduced sperm motility, but no defect in capacitation or AR [12]. Interestingly, Defb15 has an extended carboxyl tail containing an extra cysteine and six potential serine or threonine residues that would support O-linked glycosylation, which is considered a key feature of the function of DEFB126 in human sperm [13]. However, the motility defect described in the sperm isolated from DEFB126 homozygous men is quite different to the phenotype we describe here. Unlike Tollner’s study, where the sperm from homozygous men only display abnormal motility when tested in the cervical mucus mimic using viscous hyaluronic acid, our Defb D9/DefbD9 derived sperm have an obvious motility defect even in isolation medium.
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Interactions between urinary 4-tert-octylphenol levels and metabolism enzyme gene variants on idiopathic male infertility.

Interactions between urinary 4-tert-octylphenol levels and metabolism enzyme gene variants on idiopathic male infertility.

Through information gained from PubMed and Hapmap, we identified twenty potential functional polymorphisms in metabo- lism enzymes: CYP1A1 rs1048943, CYP2B6 rs3760657, rs2054675, rs707265 and rs1042389, CYP2C8 rs1058932, CYP2C9 rs4918758, CYP2C19 rs3814637, rs4986894 and rs11568732, CYP2S1 rs3810171 and rs338583, NAT1 rs7845127and rs10888150, NAT2 rs1799930, rs1799931, rs4646246 and rs4646243, SULT1E1 rs4149525 and rs3736599 (Table 1). All selected single nucleotide polymorphism (SNPs) have reported minor allele frequencies (MAF) of .0.05 in Han-Chinese population and are located in potential functional areas. In the case of multiple SNPs in the same haplotype block (linkage coefficient r 2 .0.8), only one was selected. Eight SNPs (rs2054675, rs707265, rs1042389, rs4986894, rs11568732, rs338583, rs10888150, rs1799931) were genotyped by using TaqMan SNP Genotyping Assays (Biosteed, Nanjing, China) and the other twelve SNPs (rs1048943, rs3760657, rs1058932, rs4918758, rs3814637, rs3810171, rs7845127, rs1799930, rs4646246, rs4646243, rs4149525 and rs3736599) were genotyped by GenomeLab SNPstream high throughput 12-plex genotyping Platform (Beckman Coulter, Fullerton, CA) following the manufacturer’s instructions [24]. For quality control, 10% of the samples were randomly genotyped again, and the repeatability was 100%.
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Recurrent Microdeletions at Xq27.3-Xq28 and Male Infertility: A Study in the Czech Population.

Recurrent Microdeletions at Xq27.3-Xq28 and Male Infertility: A Study in the Czech Population.

asthenoteratozoospermia, 4/81, i.e. 4.9%) and one subject with normal sperm concentration, but asthenozoospermia. Therefore in the Czech cohort, microdeletion frequency in patients appears lower compared to the South European cohort. On the other hand, microdeletion fre- quency in controls of this study (Xcnv64 15/131, i.e. 11.5%, Xcnv69 6/131, i.e. 4.6%) is strik- ingly high compared to the population sample of Southern Europe (3.1% and 1.6% for Xcnv64 and Xcnv69 respectively). PCR errors could be a potential source of false positivity, however, the Xcnv64 region failed to amplify even when annealing temperature was lowered down to 53°C or using different DNA polymerase, while other PCR products on X chromosome, in vicinity of the deleted region, were amplified under standard conditions (Table 3). Moreover, Xcnv69 was validated by deletion bridging PCR for types A and B. The type of semen abnor- mality in Xcnv64 and Xcnv69 carriers corresponds well between the cohorts, given the limits of our cohort size. There is also no substantial difference in the general type of abnormality in the whole patient group (our cohort: 23 azoospermic, 81 oligospermic (with or without astheno- zoospermia and teratozoospermia) and 3 asthenozoospermic men; South European cohort: 163 azoospermic, 463 oligospermic men and one with normal sperm concentration, but infer- tile subject. Ratio of the oligozoospermic to azoospermic patients was not different in our cohort in comparison to the South European cohort (χ 2 test P = 0.36). This was despite the fact that our study used the 2010 WHO guidelines, while the South European study used less strict 1999 guidelines for sperm concentration.
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Male infertility in spinal cord trauma

Male infertility in spinal cord trauma

Several authors have investigated the role of seminal plasma as the cause of poor sperm quality. When mixed with spermatozoa from normal men, semi- nal plasma from patients with SCT promotes a decrease in their motility. Contrarily, the addition of seminal plasma from normal men improves sperm motility in patients with SCT (48). Spermatozoa collected from the vas deferens of patients with spinal cord lesions show higher motility when compared to those obtained from the ejaculate and seminal vesicles, suggesting that the worsening quality could be associated with factors that are present in prostate or seminal vesicle secre- tions (49,50). Changes in the seminal plasma have been found following SCT installation, such as reduced lev- els of fructose levels, albumin, glutamic oxaloacetic transaminase, alkaline phosphatase and prostate-spe- cific antigen (PSA), and increased levels of chloride (51,52), reactive oxygen species (ROS) (53) and cytokine (54,55). The low fructose concentration in the semen from patients with SCT, which is a major energy source for the spermatozoa, has been pointed out as a co-factor in asthenospermia. Reactive oxygen species such as superoxide anion, hydrogen peroxide, peroxyl and hydroxyl are being correlated with low viability and morphological changes in spermatozoa (56). High cytokines (54) indicate an immunological ground for infertility. Cohen et al. (55) reported im- provement in sperm motility following cytokine inac- tivation by monoclonal antibodies. Anti-sperm antibod- ies have also been reported as a potential cause of low seminal quality due to their high titers in such situa- tions (57).
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Occupational exposure to bisphenol A (BPA): a reality that still needs to be unveiled

Occupational exposure to bisphenol A (BPA): a reality that still needs to be unveiled

correlated with decreased semen quality and male infertility, for which induction of germ cell apoptosis is considered a primary contributing factor [101]. BPA-induced apoptosis was previously observed in human trophoblastic cells in vitro for a concentration of 1 µM [102] as well as in rat ovarian cells in vivo after prolonged exposure [103], indicating a potential negative role in reproductive function. Occupational exposure to BPA resulted in increased urine BPA levels significantly associated with decreased sperm concentration, total sperm count, vitality and motility [59]. Liu and co-workers demonstrated that the presence of elevated BPA urinary levels is also associated with alterations of relevant laboratory parameters that may contribute to male infertility, namely prolactin, estradiol and sex hormone-binding globulin (SHBG) [62]. Increased mean serum BPA concentration has also been associated with decreased mean androstenedione (AD) level (0.18 ng/mL, 95 % CI − 0.22 to − 0.13) and increased mean serum sex hormone-binding globulin (SHBG) level (2.79 nmol/L, 95% CI 2.11–3.46) in male workers from exposed to epoxy resin factories [77]. Moreover, in male exposed workers sperm methylation level of long interspersed nucleotide elements (LINE-1), a marker of global genome methylation status, was significantly decreased when compared to unexposed workers [61]. Interestingly, previous reports have demonstrated that BPA exposure in the range detected both in environmental and occupational levels induces transcriptional deregulation of LINE1 in cellular models (HUVEC and HT29) associated with global transcription deregulation [104]. Moreover, the activation of mitogen-activated protein kinases (MAPK) are believed to be involved in the damaging effects of BPA on testicular function associated with disruption of the Sertoli cell tight junction (TJ)-barrier function at the blood-testis barrier. Therefore the use of specific inhibitors against MAPK are being considered a possibility to "manage" the negative health effects and/or "protect" occupationally exposed individuals [105].
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(Epi)genetic characterization of the AZFc region of the Y chromosome : new links to male fertility

(Epi)genetic characterization of the AZFc region of the Y chromosome : new links to male fertility

recombination between internal AZFc amplicons have already been described (Fernandes et al., 2002; Repping et al., 2003b; Fernandes et al., 2004; Machev et al., 2004; Repping et al., 2004). These partial deletions are associated to extremely variable phenotypes, ranging from normo to azoospermia, making definite conclusions on their real impact for male fertility a source of controversy (Ferlin et al., 2005b; Hucklenbroich et al., 2005; Lynch et al., 2005; Ravel et al., 2006). In addition, partial deletion rates also vary considerably between populations, with some being fixed with no apparent effect on fertility in several Y-lineages, further confounding association studies (Repping et al., 2003b; Fernandes et al., 2004; Repping et al., 2004). However, the source of the variable phenotypes attributed to partial deletions may lie in the specificities of AZFc’s structure. Large-scale variations of AZFc architecture as a result of inversions and duplications/deletions are estimated to occur at particularly elevated levels (Repping et al., 2006). By adding frequent gene conversions (Rozen et al., 2003), AZFc’s variability rate may reach an unprecedented scale for a human non-satellite locus. This implies that the available AZFc reference sequence may only represent a fraction of the plethora of possible rearrangements. Therefore, partial AZFc deletions by resulting from variable amplicon recombinations and by occurring on extremely diverse AZFc structural backgrounds may result in a heterogeneous pool of deletion products with varying gene copy content. Since human duplicate genes have been shown to diverge rapidly in their spatial expression (Makova and Li, 2003), it has been proposed that the different copies of AZFc genes vary in terms of functional properties (Fernandes et al., 2002; Machev et al., 2004). Thus, characterizing exactly which copies remain in partially deleted chromosomes of fertile and infertile men may explain the variable phenotypes associated to these deletions and might shed new light on the functional roles of the various copies of AZFc genes.
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Int. braz j urol.  vol.40 número4

Int. braz j urol. vol.40 número4

Semen analysis is the corner stone of infertility evaluation as it provides information on the functional status of the seminiferous tubules, epididymis and accessory sex glands. The methods on how the human semen should be evaluated are provided by the World Health Organization, which periodically releases manuals that include specific protocols and reference standards. In 2010, the WHO published new criteria for human semen characteristics that were markedly lower than those previously reported. In this review initially it is discussed the limitations of semen analysis as a surrogate measure of a man’s ability to father a pregnancy. Secondly, it is analyzed methodology issues that could explain why the newly released reference values were different from those earlier reported. Thirdly, it is speculated on the likely effects of the 2010 WHO criteria in the management of male infertility. Due to the several inherent limitations of semen analysis as a surrogate marker of male infertility, physicians should exercise caution when interpreting results. A template for semen analysis reports that incorporates the distribution of the semen characteristics of recent fathers in centiles rather than solely the minimum thresholds could aid clinicians to better understand how a given patient results compare with the reference population. Importantly, a male infertility evalua- tion must go far beyond a simple semen analysis, as it has to be complemented with a proper physical examination, a comprehensive history taking, and relevant endocrine, genetic, and other investigations.
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Cad. Saúde Pública  vol.27 número9

Cad. Saúde Pública vol.27 número9

study aimed at understanding the dynamics of disclosure of HIV diagnosis to partners, family members, friends, and coworkers in New York City, various codes for indirectly communicating one’s positive serostatus are used, such as leav- ing medication in plain view in the living room and educating partners on the need for people in general to protect themselves with condoms; such strategies are more common among ho- mosexual men, among whom HIV prevalence is often high. In their study, those that adopted this way of disclosing their diagnosis felt that veiled messages met the moral imperative of commu- nicating seropositive status; others considered such approaches morally unacceptable, a half-lie. In contexts of anonymous or casual sex (hetero- sexual or homosexual), silencing on seropositive status was viewed as more acceptable; speaking about infection in these situations was perceived as anti-erotic. On the other hand, more lasting re- lationships assume or require trust in order to be establish, and non-disclosure could perpetuate mistrust; meanwhile, disclosure to one partner could help build the confidence what would tend to stimulate disclosure to others.
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KATNAL1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility.

KATNAL1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility.

Spermatogenesis is a complex process reliant upon interactions between germ cells (GC) and supporting somatic cells. Testicular Sertoli cells (SC) support GCs during maturation through physical attachment, the provision of nutrients, and protection from immunological attack. This role is facilitated by an active cytoskeleton of parallel microtubule arrays that permit transport of nutrients to GCs, as well as translocation of spermatids through the seminiferous epithelium during maturation. It is well established that chemical perturbation of SC microtubule remodelling leads to premature GC exfoliation demonstrating that microtubule remodelling is an essential component of male fertility, yet the genes responsible for this process remain unknown. Using a random ENU mutagenesis approach, we have identified a novel mouse line displaying male-specific infertility, due to a point mutation in the highly conserved ATPase domain of the novel KATANIN p60-related microtubule severing protein Katanin p60 subunit A-like1 (KATNAL1). We demonstrate that Katnal1 is expressed in testicular Sertoli cells (SC) from 15.5 days post-coitum (dpc) and that, consistent with chemical disruption models, loss of function of KATNAL1 leads to male-specific infertility through disruption of SC microtubule dynamics and premature exfoliation of spermatids from the seminiferous epithelium. The identification of KATNAL1 as an essential regulator of male fertility provides a significant novel entry point into advancing our understanding of how SC microtubule dynamics promotes male fertility. Such information will have resonance both for future treatment of male fertility and the development of non-hormonal male contraceptives.
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