The possible association of clusterin fucosylation changes with male fertility disorders

AbstractIn the seminal plasma (n = 118) and serum (n = 90) clusterin (CLU) the fucosylation and the expression of selected fucosyltransferases (FUTs) were analyzed. Samples from infertile men were divided into groups based on the results of the standard semen analysis: normozoospermic (N), teratozoospermic (T), asthenoteratozoospermic (AT) and oligoasthenoteratozoospermic (OAT). The CLU fucosylation was analyzed using lectin-ELISAs with biotinylated lectins specific to α1,3-, α1,2-linked antennary fucose, and α1,6-linked core fucose (LTA, UEA, and LCA, respectively). The concentrations of FUT3 and FUT4, reflecting the expression of Le oligosaccharide structures, were measured using ELISA tests. The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility. Lack of similarities between levels of examined parameters in blood serum and seminal plasma may suggest the differences in mechanisms leading to glycoproteins glycosylation. It confirmed the observed differences in concentrations of seminal plasma CLU, FUT3, and FUT4 between the OAT group and N, T, AT groups, indicating that decreased sperm count may be related to these parameters expression. The serum CLU concentrations and expression of core fucose and fucose α1,2-linked in CLU, seem to be good markers differentiating normozoospermic men from those with abnormal sperm parameters, which was not observed for seminal plasma.

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Exploratory Analysis in the Differences in Blood Serum and Seminal Plasma of Adipose-Tissue Related Peptides in Obese and Non-Obese Men and Their Correlations With Semen Parameters

Frontiers in Endocrinology ◽

10.3389/fendo.2021.681939 ◽

2021 ◽

Vol 12 ◽

Author(s):

Cristina Antinozzi ◽

Marco Lista ◽

Luisa Caponecchia ◽

Pietro Salacone ◽

Carlo Minganti ◽

...

Keyword(s):

Male Infertility ◽

Blood Serum ◽

Seminal Plasma ◽

Sperm Count ◽

Normal Weight ◽

Semen Parameters ◽

C Peptide ◽

Progressive Motility ◽

Obese Subjects ◽

Pai 1

ObjectivesEvaluating the relationship between circulating metabolic biomarkers and semen parameters in obese, overweight and normal-weight patients.MethodsPatients were recruited at the “Andrology and Pathophysiology of Reproduction Unit”, in Santa Maria Goretti Hospital. Divided into three groups were 98 participants (obese, overweight and normal-weight patients) according to BMI and were analyzed for three adipokines and six hormone peptides in blood serum and seminal plasma using Luminex assay. Standard semen analysis was performed for ejaculate volume, sperm concentration, total sperm count, motility, morphology and leukocytes.ResultsIn all groups of subjects, we observed a higher concentration of blood serum c-peptide, GIP, PAI-1, leptin, ghrelin and GLP-1 in comparison to seminal plasma; differently, higher levels in seminal plasma were observed for insulin and visfatin. In comparison to the non-obese subjects, obese subjects showed a higher blood serum concentration of c-peptide, GLP-1, GIP and leptin and a higher concentration of seminal plasma of GIP and insulin. Total sperm count, progressive motility, motility, and atypical forms directly correlated with PAI-1 and visfatin, whereas GLP-1 directly correlated only with total progressive motility.ConclusionObese men showed a different pattern of blood serum and seminal plasma adipokines and hormone peptides concentrations in comparison to normal-weight men. Furthermore, these molecules correlated with functional seminal parameters. Our findings support the option to consider these molecules as new biomarkers and pharmacological targets for a new therapeutic approach in male infertility. However, further studies identifying other potential biomarkers of male infertility with important clinical implication and characterizing their mechanisms of action are mandatory.

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Seminal Plasma Clusterin as a Biomarker for Spermatogenesis in Varicocele Patients before and after Varicocelectomy

QJM ◽

10.1093/qjmed/hcaa046.015 ◽

2020 ◽

Vol 113 (Supplement_1) ◽

Author(s):

H M A Saleh ◽

A A Afify ◽

W A Ahmed ◽

M S Daruish

Keyword(s):

Seminal Plasma ◽

Sperm Count ◽

Semen Analysis ◽

Progressive Motility ◽

Infertile Men ◽

Pampiniform Plexus ◽

Significant Difference ◽

Before And After ◽

Sperm Development ◽

High Concentrations

Abstract Introduction a varicocele is an abnormally dilated pampiniform plexus of veins. Hyperthermia, oxidative stress, and elevated apoptotic index have been described in men with variocele and infertility. Clusterin (Clu) is a chaperone-like glycoprotein which is synthesized by Sertoli cells in high concentrations and is deposited onto the membranes of and mature spermatozoa, giving rise to the possibility that it has a role in sperm development. Secreted form of clusterin is a powerful anti-apoptotic. Aim To explore clusterin level in seminal plasma of infertile men with varicocele in comparison to normal healthy fertile subjects and to compare the seminal plasma clusterin level before and after varicocelectomy Methods The study included 25 patients suffering from varicocele with infertility (whether primary or secondary) for 12 months, and 10 healthy volunteers of matched age and sex as control. For all the patients Sub-inguinal varicocelectomy was done. Semen analysis, and seminal plasma clusterin assay were carried out before and three months after varicocelectomy. Results there was a statistically significant difference between patients and controls as regards sperm count, progressive motility, and seminal plasma clusterin (P < 0.01). Three months after varicocelectomy, the sperm count had a highly significant improvement in the patient’s group (Mean= 17.90 + 8.86) compared to a preoperative count (Mean= 11.43 + 7.56). There was a highly significant improvement in post-operative progressive motility in the patient’s group (Mean= 34.5 + 20.2) compared to a preoperative progressive motility (Mean= 22.05 + 15.5). Post-operative clusterin showed a highly significant elevation in the patient’s group postoperative (Mean= 10.73 + 4.5) compared to a preoperative clusterin (Mean= 6.68 + 3.8). Conclusion Based on our study we could suggest another way of contribution of varicocele to male infertility by affecting seminal plasma clusterin level.

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Role of Glutathione in Male Infertility

Bangladesh Journal of Medical Biochemistry ◽

10.3329/bjmb.v4i2.13772 ◽

2013 ◽

Vol 4 (2) ◽

pp. 20-25

Author(s):

ZU Naher ◽

SK Biswas ◽

FH Mollah ◽

M Ali ◽

MI Arslan

Keyword(s):

Male Infertility ◽

Seminal Plasma ◽

Antioxidant Defense ◽

Sperm Morphology ◽

Sperm Count ◽

Antioxidant Systems ◽

Infertile Male ◽

Semen Volume ◽

Infertile Group ◽

Male Subjects

Infertility is a worldwide problem and in almost 50% of cases infertility results from abnormality of the male partners. Apart from endocrine disorders, definitive cause and mechanism of male infertility is not clear in many cases. Recent evidence indicates that imbalance between pro-oxidant stress and antioxidant defense plays an important role in the pathogenesis of male infertility. Among the endogenous antioxidant systems, reduced glutathione (GSH) plays a significant role in the antioxidant defense of the spermatogenic epithelium, the epididymis and perhaps in the ejaculated spermatozoa. The current study was therefore designed to evaluate any association that may exist between GSH levels and male infertility. Infertile male patients (having female partners with normal fertility parameters; n=31) and age- matched healthy male fertile control subjects (n=30) were included in this study. In addition to medical history, semen analyses including semen volume, sperm count, motility and morphology were done for each subject. As a measure of antioxidant capacity erythrocyte and seminal plasma GSH concentrations were measured by Ellman's method in fertile and infertile male subjects. The infertile subjects were similar to fertile subjects in terms of age. However, semen volume and sperm count was found significantly lower (p<0.001) in infertile males compared with healthy fertile male subjects. Percentage of subjects with abnormal sperm morphology and motility were found higher in infertile group compared with fertile group. The median (range) erythrocyte GSH level did not differ between the two groups (12.62 (0.67-29.82) versus 13.93 (2.10-21.08) mg/gm Hb). However, the seminal plasma GSH level was found markedly suppressed in infertile group (1.64 (0.23-7.50)) compared with fertile group (4.26 (2.32-7.50)) mg/dl (p<0.001). In the present study seminal plasma GSH level was found markedly suppressed along with abnormal values for semen volume, sperm concentration and sperm morphology and motility in infertile subjects compared with fertile subjects. This finding indicates that low level of seminal plasma GSH level may be associated with male infertility. DOI: http://dx.doi.org/10.3329/bjmb.v4i2.13772 Bangladesh J Med Biochem 2011; 4(2): 20-25

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Is there a place for nutritional supplements in the treatment of idiopathic male infertility?

Archivio Italiano di Urologia e Andrologia ◽

10.4081/aiua.2014.3.164 ◽

2014 ◽

Vol 86 (3) ◽

pp. 164 ◽

Cited By ~ 16

Author(s):

Davide Arcaniolo ◽

Vincenzo Favilla ◽

Daniele Tiscione ◽

Francesca Pisano ◽

Giorgio Bozzini ◽

...

Keyword(s):

Male Infertility ◽

Sperm Count ◽

Nutritional Supplements ◽

Semen Parameters ◽

Male Factor ◽

Treatment Regimens ◽

Idiopathic Male Infertility ◽

Infertile Men ◽

Wide Variability

Objective: Infertility affects 15% of couples in fertile age. Male factor is a cause of infertility in almost half of cases, mainly due to oligoasthenoteratozoospermia (OAT). The purpose of this study is to review the effects of nutritional supplements as medical treatment for idiopathic male infertility. Material and methods: A Pub Med and Medline review of the published studies utilizing nutritional supplements for the treatment of male infertility has been performed. Results: Clinical trials on Vitamin E, Vitamin A, Vitamin C. Arginine, Carnitine, N-Acetyl-Carnitine, Glutathione, Coenzyme Q10, Selenium and Zinc were reviewed. Although there is a wide variability in selected population, dose regimen and final outcomes, nutritional supplements both alone and in combination seems to be able to improve semen parameters (sperm count, sperm motility and morphology) and pregnancy rate in infertile men. Conclusions: There are rising evidences from published randomized trials and systematic review suggesting that nutritional supplementation may improve semen parameters and the likelihood of pregnancy in men affected by OAT. This improvement, however, is not consistent and there is a wide variation in the treatment regimens used. Well designed and adequately powered RCTs are needed to better clarify the role of nutritional supplements as treatment for male infertility.

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The Tug1 Locus is Essential for Male Fertility

10.1101/562066 ◽

2019 ◽

Cited By ~ 2

Author(s):

Jordan P. Lewandowski ◽

Gabrijela Dumbović ◽

Audrey R. Watson ◽

Taeyoung Hwang ◽

Emily Jacobs-Palmer ◽

...

Keyword(s):

Male Fertility ◽

Sperm Morphology ◽

Sperm Count ◽

Initial Study ◽

Genomic Region ◽

Complete Penetrance ◽

Abnormal Sperm ◽

Lncrna Locus ◽

Mammalian Genomes ◽

Taurine Upregulated Gene 1

ABSTRACTBackgroundSeveral long noncoding RNAs (lncRNAs) have been shown to function as central components of molecular machines that play fundamental roles in biology. While the number of annotated lncRNAs in mammalian genomes has greatly expanded, their functions remain largely uncharacterized. This is compounded by the fact that identifying lncRNA loci that have robust and reproducible phenotypes when mutated has been a challenge.ResultsWe previously generated a cohort of 20 lncRNA loci knockout mice. Here, we extend our initial study and provide a more detailed analysis of the highly conserved lncRNA locus, Taurine Upregulated Gene 1 (Tug1). We report that Tug1 knockout male mice are sterile with complete penetrance due to a low sperm count and abnormal sperm morphology. Having identified a lncRNA loci with a robust phenotype, we wanted to determine which, if any, potential elements contained in the Tug1 genomic region (DNA, RNA, protein, or the act of transcription) have activity. Using engineered mouse models and cell-based assays, we provide evidence that the Tug1 locus harbors three distinct regulatory activities – two noncoding and one coding: (i) a cis DNA repressor that regulates many neighboring genes, (ii) a lncRNA that can regulate genes by a trans-based function, and finally (iii) Tug1 encodes an evolutionary conserved peptide that when overexpressed impacts mitochondrial membrane potential.ConclusionsOur results reveal an essential role for the Tug1 locus in male fertility and uncover three distinct regulatory activities in the Tug1 locus, thus highlighting the complexity present at lncRNA loci.

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The polymorphisms of NR5A1 gene in azoospermic men in Sichuan, China

10.21203/rs.3.rs-37121/v1 ◽

2020 ◽

Author(s):

Lanyue Cui ◽

Jiaoyu He ◽

Junhang Deng ◽

Zhilin Song ◽

Qiufu Li ◽

...

Keyword(s):

Male Infertility ◽

Missense Mutation ◽

Karyotype Analysis ◽

Semen Analysis ◽

Transcriptional Regulator ◽

Organ Development ◽

Steroidogenic Factor 1 ◽

Beta Strand ◽

Susceptibility Factor ◽

Infertile Men

Abstract Background: Steroidogenic factor 1 (SF1, NR5A1) is a key transcriptional regulator involved in the hypothalamic-pituitary-steroidogenic organ development. Recently, heterozygous mutations in NR5A1 were found may contribute to the male infertility aetiology. Here, we investigated the association of polymorphisms in NR5A1 gene with azoospermic men in Sichuan, China. Methods: We have performed the NR5A1 gene direct secquencing in a cohort of 102 well-characterised idiopathic Chinese azoospermic infertile men versus 103 fertile men, who were selected by Semen analysis, Karyotype analysis and Y-chromosomal AZF deletion screening. We identified two previously described missense p. Results: Gly146Ala (rs1110061; c.437 G>C) and p.Arg313His (c.938G>A), and the frequency of 437C ( [OR] 1.846, 95% [CI] 1.227-2.778, P=0.003), 437GC (OR =1.884 , 95% CI =1.037-3.422 , P =0.037 ) and 437CC (OR =3.586 , 95% CI =1.397-9.206 , P =0.006 ) were found to be increased significantly in azoospermic patients while no mutations in control .Moreover, one novel heterozygous p.Ser322ILe (c.965 G >A) missense mutation was found in 8 patients which highly conserved serine to isoleucine shown in the Beta strand domain on SF-1 protein. Conclusions: This is the first study, according to our knowledge, to investigate the association between the polymorphisms of NR5A1 gene and azoospermic men in China, and these results suggest that the Gly146Ala polymorphism may be a susceptibility factor for the azoospermic men in Sichuan, China.

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Impact of oxidative stress on semen parameters in normozoospermic infertile men: a case–control study

African Journal of Urology ◽

10.1186/s12301-020-00061-6 ◽

2020 ◽

Vol 26 (1) ◽

Author(s):

Ayad Palani ◽

Ahmed Alahmar

Keyword(s):

Oxidative Stress ◽

Uric Acid ◽

Male Infertility ◽

Seminal Plasma ◽

Case Control Study ◽

Case Control ◽

Semen Parameters ◽

Infertile Men ◽

Total Antioxidant ◽

Control Study

Abstract Background Oxidative stress has been implicated in male infertility through decrease in sperm quality. However, men with normal semen parameters (normozoospermia) may be unable to fertilize their partners even when they have normal sperm function. Thus, they would be considered infertile. The purpose of this study was to investigate the role of oxidative stress in the pathogenesis of unexplained male infertility. Methods In this case–control study, infertile men with normozoospermia (n = 46) and fertile control group (n = 21) underwent seminal fluid analyses according to WHO 2010 criteria. Serum and seminal plasma levels of total antioxidant capacity (TAC), glutathione, malondialdehyde, uric acid and albumin were also measured using colorimetric methods. Results The level of total antioxidant capacity in both serum and seminal plasma was significantly lower in normozoospermic infertile men in comparison with fertile group (p < 0.0001). However, no significant differences were observed in serum and seminal plasma levels of glutathione, uric acid, albumin and malondialdehyde between infertile and fertile groups. Conclusion Low TAC level induces oxidative stress and consequently causes sperm dysfunction and male infertility. Estimation of TAC can be a useful tool in the diagnosis of male infertility. Antioxidant supplementation should be considered in the treatment of oxidative stress-induced male infertility.

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Prevalence and Patterns of Male Infertility Based on Semen Analysis in Patients Visiting Massawa Hospital; Eritrea: Cross-Sectional Study; 2020

10.21203/rs.3.rs-401307/v1 ◽

2021 ◽

Author(s):

Berhe Tesfai ◽

Fitsum Kibreab ◽

Hailemichael Gebremariam ◽

Liwam Abraham

Keyword(s):

Male Infertility ◽

Sperm Motility ◽

Sperm Count ◽

Semen Analysis ◽

Male Factor Infertility ◽

Male Factor ◽

Cross Sectional ◽

Semen Volume ◽

Primary Type ◽

Study Participants

Abstract Background Semen analysis is the first step to identify male factor infertility. World Health Organization estimates that male factor accounts for 50% of couple sub-fertility. The objective of this study was to determine the prevalence and patterns of male factor infertility based on semen analysis in patients visiting Massawa Hospital with infertility complaints. Methods It was a retrospective, descriptive cross sectional hospital based type of study with a census sampling method. Patient’s medical records and hospital laboratory register were used to retrieve semen analysis results of patients from June 2018 to June 2020. Ethical approval was obtained from the Ministry of Health Research and Ethical Review Committee. Confidentiality of patients records kept was secured and consent was obtained from study participants to use their data. Results were presented in frequency, tables and p value < 0.05 was considered significant. Results A total of 112 patients data was analyzed in the study with 49.1% were aged between 20 to 30 years. The prevalence of male factor infertility in these patients was found to be 42% and 79.5% of them had primary type of infertility. Of the study participants; 63 (56.3%), 72 (64.3%) and 70 (62.5%) had sperm count < 15 million sperms/ml, sperm motility < 40 % and morphology of < 60% respectively. One tenth, 15 (13.4%) of the patients had a semen volume of < 1.5ml/ejaculate, out of which 13(86.7%) had primary type of infertility. Moreover; 72 (64.3%) patients had total sperm count/ejaculate of < 39 million and 59 (82%) of these had primary type of infertility. In addition; 50.8% and 50% of patients aged 20 to 30 years had a sperm count < 15 million/ml and sperm motility of < 40% respectively. Conclusion The prevalence of male factor infertility was slightly higher and was dominated with primary infertility. Most patients had lower sperm count, sperm motility but higher semen volume, and majority of the patients with abnormal sperm results were aged between 20 to 30 years. Further prospective researches to determine the risk factors for male infertility and introducing assisted type of fertility in Eritrea are highly recommended.

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Influence of Lifestyle and Environmental Factors on Semen Quality in Ghanaian Men

International Journal of Reproductive Medicine ◽

10.1155/2020/6908458 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Richard Michael Blay ◽

Abigail Duah Pinamang ◽

Augustine E. Sagoe ◽

Ewurama Dedea Ampadu Owusu ◽

Nii Koney-Kwaku Koney ◽

...

Keyword(s):

Environmental Factors ◽

Male Infertility ◽

Sperm Motility ◽

Semen Quality ◽

Sperm Quality ◽

Sperm Count ◽

Semen Analysis ◽

Reproductive Age ◽

Adult Males ◽

Lifestyle Habits

Introduction. Male infertility is known to contribute about half of all infertility cases. In Ghana, the prevalence of male infertility is higher (15.8%) than in females (11.8%). Sperm quality is associated with the likelihood of pregnancy and known to be the cause of male fertility problems 90% of the time. Exposure to certain environmental factors reduces semen quality in men. The study examined the effects of environmental and lifestyle factors on semen quality in Ghanaian men. Materials and Methods. This was a cross-sectional study involving 80 apparent healthy adult males in their reproductive age. Participants were males referred to the laboratory (Immunology Unit of the Korle-Bu Teaching Hospital) for semen analysis test and/or culture and sensitivity. Participants were made to fill out a questionnaire which entailed selected environmental factors (accidents or trauma, exposure to chemicals, radiation, and heat) and lifestyle habits (including alcohol consumption, smoking, and whether participants sat more or less than 4 hours per day). Semen samples were then collected by masturbation into sterile containers and analysed in accordance with WHO guidance for semen analysis within 60 minutes after ejaculation and collection. Results. About 69% of participants had semen pH within the normal range compared to 15% whose pH were lower than 7.2. There was a significantly high number of immotile sperm cells ( p value = 0.017) in participants who sat for more than 4 hours as compared to those that sat for less than 4 hours in a day. Active sperm motility and viability showed significant increase ( p value = 0.002 and 0.009, respectively) in participants who kept their cell phones in their side pockets. Smoking produced a twofold decrease in sperm count as smokers had a significantly lower sperm count ( 12.28 ± 10.95 × 10 6 /ml) compared to the smoke-free ( 23.85 ± 22.14 × 10 6 /ml). For exposure to STDs, no significant differences were recorded among study groups concerning semen quality. Conclusion. Sperm quality in Ghanaian men is associated with lifestyle habits. Smoking and sitting for long hours influenced sperm motility and count, respectively. Knowledge of the factors that influence sperm quality in this geographical region can contribute to informed decisions on effective management of infertility in Ghanaian men.

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Seminal Plasma Proteomic Biomarkers of Oxidative Stress

International Journal of Molecular Sciences ◽

10.3390/ijms21239113 ◽

2020 ◽

Vol 21 (23) ◽

pp. 9113

Author(s):

Rossella Cannarella ◽

Andrea Crafa ◽

Federica Barbagallo ◽

Laura M. Mongioì ◽

Rosita A. Condorelli ◽

...

Keyword(s):

Oxidative Stress ◽

Male Infertility ◽

Seminal Plasma ◽

Molecular Mechanisms ◽

Seminal Fluid ◽

Accessory Gland ◽

Male Accessory Gland ◽

Abnormal Sperm ◽

Clinical Conditions ◽

Biomarkers Of Oxidative Stress

The prevalence of idiopathic male infertility is high, up to 75% of patients with abnormal sperm parameters. Hence, the research of its causes is mandatory. Oxidative stress (OS) can be responsible for male infertility in 30–80% of cases. In recent years, seminal plasma (SP) proteomics has developed as a useful tool to provide biomarkers of specific diseases. This systematic review aims to collect the available evidence on the changes of SP proteome in patients exposed to OS to provide possible SP biomarkers of sperm OS. To accomplish this, the following keyterms “seminal fluid proteome”, “seminal plasma proteome”, “oxidative stress”, and “sperm oxidative stress” were used and 137 records were found. Among these, 17 were finally included. Nine proteins involved with OS were found overexpressed in patients with OS. Twenty-three proteins were found differentially expressed in patients with clinical conditions associated with OS, such as varicocele, male accessory gland infection/inflammation, cigarette smoke, and obesity. These proteins do not seem to overlap among the clinical conditions taken into account. We speculate that specific SP proteins may mediate OS in different clinical conditions. Altogether, these results suggest that proteomics could help to better understand some of the molecular mechanisms involved in the pathogenesis of infertility. However, further studies are needed to identify potential biomarkers of male infertility with valuable clinical significance.

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