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Scientific Reports Nov 2017Spermatogenesis is a multifactorial process that forms differentiated sperm cells in a complex microenvironment. This process involves the genome, epigenome,...
Spermatogenesis is a multifactorial process that forms differentiated sperm cells in a complex microenvironment. This process involves the genome, epigenome, transcriptome, and proteome to ensure the stability of the spermatogonia and supporting cells. The identification of signaling pathways linked to infertility has been hampered by the inherent complexity and multifactorial aspects of spermatogenesis. Systems biology is a promising approach to unveil underlying signaling pathways and genes and identify putative biomarkers. In this study, we analyzed thirteen microarray libraries of infertile humans and mice, and different classes of male infertility were compared using differentially expressed genes and functional enrichment analysis. We found regulatory processes, immune response, glutathione transferase and muscle tissue development to be among the most common biological processes in up-regulated genes, and genes involved in spermatogenesis were down-regulated in maturation arrest (MArrest) and oligospermia cases. We also observed the overexpression of genes involved in steroid metabolism in post-meiotic and meiotic arrest. Furthermore, we found that the infertile mouse model most similar to human MArrest was the Dazap1 mutant mouse. The results of this study could help elucidate features of infertility etiology and provide the basis for diagnostic markers.
Topics: Animals; Azoospermia; Down-Regulation; Gene Expression Profiling; Gene Ontology; Humans; Infertility, Male; Male; Mice; Oligospermia; Principal Component Analysis; Teratozoospermia; Up-Regulation
PubMed: 29150651
DOI: 10.1038/s41598-017-16005-0 -
Reproductive Sciences (Thousand Oaks,... Oct 2023The present study compared seminal calbindin 2 (CALB 2) levels and semen parameters in men with and without varicocele. CALB 2 is also known as calretinin and 29 kDa...
The present study compared seminal calbindin 2 (CALB 2) levels and semen parameters in men with and without varicocele. CALB 2 is also known as calretinin and 29 kDa calbindin. The study was a case-control study conducted from April (2021) to March (2022) in the andrology department at Beni-Suef University hospital. The study included four matched groups: group (I) were controls (fertile normozoospermic men without varicocele) (n=24). Group (II) were fertile normozoospermic men with varicocele (n=24). Group (III) were infertile oligoasthenoteratozoospermia (OAT) men without varicocele (n=24). Group (IV) were infertile OAT men with varicocele (n=24). The lowest levels of seminal CALB 2 were found in patients with severe oligozoospermia which showed a statistically significant difference when compared to seminal CALB 2 in patients with normal, mildly low, or moderately low sperm counts. There were significant negative correlations between sperm concentration, sperm motility and percentage of normal sperm forms and seminal CALB 2. Seminal plasma CALB 2 may play a role in the negative impact of varicocele on the semen parameters especially sperm concentration, sperm motility and percentage of sperm normal forms. Future studies are needed to verify these findings.
Topics: Humans; Male; Infertility, Male; Calbindin 2; Semen; Varicocele; Prospective Studies; Case-Control Studies; Sperm Motility; Oligospermia; Sperm Count
PubMed: 37067726
DOI: 10.1007/s43032-023-01237-5 -
BMC Medical Genomics Mar 2022Male infertility is a heterogeneous disease which can occur due to spermatogenesis defects. The idiopathic azoospermia and oligospermia are the common cause of male...
BACKGROUND
Male infertility is a heterogeneous disease which can occur due to spermatogenesis defects. The idiopathic azoospermia and oligospermia are the common cause of male infertility with unknown underlying molecular mechanisms. The aim of this study was to investigate association of idiopathic azoospermia and oligospermia with single-nucleotide polymorphisms of CATSPER1, SPATA16 and TEX11 genes in Iranian-Azeri men.
METHODS
In this case-control study, we recruited 100 infertile men (case group) and 100 fertile men (control group) from Azeri population in north western provinces, Iran, population. The genomic DNA was extracted using a proteinase K method from peripheral blood leukocytes. The genotypes analysis was conducted using tetra-primer amplification refractory mutation system-polymerase chain reaction method. The obtained data were analyzed by statistical software.
RESULTS
We found a significant difference in the frequencies of heterozygote AB and mutant homozygote BB genotypes in the CATSPER1 (rs2845570) gene polymorphism between patients and healthy controls (p < 0.05). Moreover, we observed a significant difference in the frequencies of heterozygote BA genotype in the SPATA16 (rs1515442) gene polymorphism between patients and healthy controls (p < 0.05). However, no significant difference was found in genotypes distribution of case and control groups in the TEX11 (rs143246552) gene polymorphism.
CONCLUSION
Our finding showed that the CATSPER1 (rs2845570) and SPATA16 (rs1515442) genes polymorphism may play an important role in idiopathic azoospermia and oligospermia in Iranian Azeri population. However, more extensive studies with larger sample sizes from different ethnic origins are essential for access more accurate results.
Topics: Azoospermia; Calcium Channels; Case-Control Studies; Cell Cycle Proteins; Humans; Infertility, Male; Iran; Male; Oligospermia; Polymorphism, Single Nucleotide; Vesicular Transport Proteins
PubMed: 35248021
DOI: 10.1186/s12920-022-01197-w -
Journal of Cellular and Molecular... Apr 2024Oligoasthenoteratospermia (OAT), characterized by abnormally low sperm count, poor sperm motility, and abnormally high number of deformed spermatozoa, is an important...
Oligoasthenoteratospermia (OAT), characterized by abnormally low sperm count, poor sperm motility, and abnormally high number of deformed spermatozoa, is an important cause of male infertility. Its genetic basis in many affected individuals remains unknown. Here, we found that CCDC157 variants are associated with OAT. In two cohorts, a 21-bp (g.30768132_30768152del21) and/or 24-bp (g.30772543_30772566del24) deletion of CCDC157 were identified in five sporadic OAT patients, and 2 cases within one pedigree. In a mouse model, loss of Ccdc157 led to male sterility with OAT-like phenotypes. Electron microscopy revealed misstructured acrosome and abnormal head-tail coupling apparatus in the sperm of Ccdc157-null mice. Comparative transcriptome analysis showed that the Ccdc157 mutation alters the expressions of genes involved in cell migration/motility and Golgi components. Abnormal Golgi apparatus and decreased expressions of genes involved in acrosome formation and lipid metabolism were detected in Ccdc157-deprived mouse germ cells. Interestingly, we attempted to treat infertile patients and Ccdc157 mutant mice with a Chinese medicine, Huangjin Zanyu, which improved the fertility in one patient and most mice that carried the heterozygous mutation in CCDC157. Healthy offspring were produced. Our study reveals CCDC157 is essential for sperm maturation and may serve as a marker for diagnosis of OAT.
Topics: Animals; Humans; Male; Mice; Asthenozoospermia; Infertility, Male; Mice, Knockout; Mutation; Oligospermia; Semen; Sperm Motility; Spermatozoa; Membrane Proteins
PubMed: 38509755
DOI: 10.1111/jcmm.18215 -
PloS One 2023Almost 40% of infertile men cases are classified as idiopathic when tested negative to the current diagnostic routine based on the screening of karyotype, Y chromosome...
Almost 40% of infertile men cases are classified as idiopathic when tested negative to the current diagnostic routine based on the screening of karyotype, Y chromosome microdeletions and CFTR mutations in men with azoospermia or oligozoospermia. Rare monogenic forms of infertility are not routinely evaluated. In this study we aim to investigate the unknown potential genetic causes in couples with pure male idiopathic infertility by applying variant prioritization to whole exome sequencing (WES) in a cohort of 99 idiopathic Italian patients. The ad-hoc manually curated gene library prioritizes genes already known to be associated with more common and rare syndromic and non-syndromic male infertility forms. Twelve monogenic cases (12.1%) were identified in the whole cohort of patients. Of these, three patients had variants related to mild androgen insensitivity syndrome, two in genes related to hypogonadotropic hypogonadism, and six in genes related to spermatogenic failure, while one patient is mutant in PKD1. These results suggest that NGS combined with our manually curated pipeline for variant prioritization and classification can uncover a considerable number of Mendelian causes of infertility even in a small cohort of patients.
Topics: Humans; Male; Exome; Infertility, Male; Azoospermia; Oligospermia; Mutation
PubMed: 37540677
DOI: 10.1371/journal.pone.0288336 -
Fertility Research and Practice Dec 2020Infertility is a practical concern of Africans due to social disgrace and exclusion. This meta-analysis aims to analyze the proportion of primary and secondary...
BACKGROUND
Infertility is a practical concern of Africans due to social disgrace and exclusion. This meta-analysis aims to analyze the proportion of primary and secondary infertility and identify the etiologic factors based on the studies conducted in Africa.
METHODS
An internet-based search was conducted on the following databases; PubMed/Medline, EMBASE, Cochrane library, and google scholar. Both population and institution-based studies conducted among African couples, males, and females were included. Data extraction and critical appraisal of the articles were done by two independent investigators. Meta-analysis using a random effect model was conducted by Stata version 14. Forest plot, heterogeneity test, and funnel plot for publication bias were performed.
RESULTS
The pooled proportion of primary and secondary infertility in Africa was 49.91% (I = 98.7, chi-square = 1509.01, degree of freedom = 19 and p < 0.001) and 49.79% (I = 98.7, chi-square = 1472.69, degree of freedom = 19 and p < 0.001) respectively. The pooled prevalence of the causes of infertility indicated that 54.01% and 22.26% of the infertility cases were respectively due to female and male-related problems. In 21.36% of infertility cases, both sexes were affected, while 10.4% of the causes of infertility were unexplained. The pooled prevalence of mostly reported causes of male infertility was 31% (oligospermia), 19.39% (asthenozoospermia), and 19.2% (varicocele). The most commonly identified causes of female infertility were pelvic inflammatory disease, tubal factors, and abortion with a pooled prevalence of 39.38%, 39.17%, and 36.41% respectively.
CONCLUSIONS
In Africa, the proportion of primary and secondary infertility is approximately equal. Infertility is mostly due to female-related causes like; pelvic inflammatory diseases, uterine tube related problems, and abortion. Oligospermia, asthenozoospermia, and varicocele were the commonest causes of male-related infertility. It is suggested that interpretation and utilization of these findings should consider the presence of substantial heterogeneity between the included studies.
PubMed: 33292584
DOI: 10.1186/s40738-020-00090-3 -
Asian Journal of Andrology 2016Infertility affects approximately 15% of couples, and male factor is responsible for 30%-50% of all infertility. The most severe form of male infertility is testicular... (Review)
Review
Infertility affects approximately 15% of couples, and male factor is responsible for 30%-50% of all infertility. The most severe form of male infertility is testicular failure, and the typical phenotype of testicular failure is severely impaired spermatogenesis resulting in azoospermia or severe oligozoospermia. Although the etiology of testicular failure remains poorly understood, genetic factor typically is an underlying cause. Modern assisted reproductive techniques have revolutionized the treatment of male factor infertility, allowing biological fatherhood to be achieved by many men who would otherwise have been unable to become father to their children through natural conception. Therefore, identifying genetic abnormalities in male is critical because of the potential risk of transmission of genetic abnormalities to the offspring. Recently, along with other intense researches ongoing, whole-genome approaches have been used increasingly in the genetic studies of male infertility. In this review, we focus on the genetics of testicular failure and provide an update on the advances in the study of genetics of male infertility.
Topics: Azoospermia; Chromosome Deletion; Chromosomes, Human, Y; Humans; Hypogonadism; Hypopituitarism; Infertility, Male; Kallmann Syndrome; Klinefelter Syndrome; Male; Male Urogenital Diseases; Oligospermia; Sex Chromosome Aberrations; Sex Chromosome Disorders of Sex Development; Testicular Diseases; Translocation, Genetic; Vas Deferens
PubMed: 27048782
DOI: 10.4103/1008-682X.178857 -
Andrology Nov 2019The human leukocyte antigen (HLA) locus includes several genes with key roles in antigen presentation and immune response, some of them inclusively found to be...
BACKGROUND
The human leukocyte antigen (HLA) locus includes several genes with key roles in antigen presentation and immune response, some of them inclusively found to be associated with non-obstructive azoospermia. Still, HLA connections to other infertility phenotypes such as semen hyperviscosity (SHV), asthenozoospermia (AST), and oligozoospermia (OLI) have been often neglected.
OBJECTIVES
In this work, we aimed to evaluate the association of HLA class I and II genes with SHV, AST, and OLI phenotypes while exploring a possible role in an adaptive immune response to sexually transmitted diseases (STD).
MATERIALS AND METHODS
Whole-exome sequencing was performed in a Portuguese cohort of 71 infertility cases and 68 controls, followed by HLA typing using a specific software-HLA*PRG:LA tool. Molecular screenings of seven STD were carried out in a subset of 72 samples (30 cases and 42 controls).
RESULTS
Statistical tests uncovered three protective alleles: HLA-A*11:01, associated with all forms of male infertility (p = 0.0006); HLA-DQB1*03:02 with SHV and OLI (P = 0.0303, P = 0.0153); and HLA-A*29:02 with OLI (p = 0.0355), which was found to interfere in sperm number together with HPV (p = 0.0313). Five risk alleles were also identified: two linked with SHV (HLA-B*50:01, p = 0.0278; and HLA-C*06:02, p = 0.0461), another one with both SHV and OLI (HLA-DQA1*05:01, P = 0.0444 and P =0.0265), and two with OLI (HLA-C*03:03, p = 0.0480; and HLA-DQB1*03:01, p = 0.0499). Here, HLA-C*03:03 carriers tend to be HPV infected.
CONCLUSIONS
The application of HLA*PRG:LA tool to the study of male infertility provided novel insights for an HLA correlation with semen quality, namely among SHV and OLI phenotypes. The discovery of an HLA-A*29:02/HPV crosstalk, together with former reports of HLA alleles conferring resistance-susceptibility to diverse human pathogens, raises the hypothesis of a mechanistic link between male infertility, HLA polymorphism, and host response to STD.
Topics: Adult; Asthenozoospermia; Azoospermia; Gene Dosage; Gene Expression Profiling; Genetic Predisposition to Disease; HLA-A Antigens; HLA-B Antigens; HLA-C Antigens; HLA-DQ beta-Chains; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Humans; Male; Oligospermia; Semen Analysis; Sexually Transmitted Diseases; Sperm Motility; Transcriptome
PubMed: 31002754
DOI: 10.1111/andr.12625 -
Clinical Epigenetics Oct 2018Testicular germ cell tumor such as seminoma is strongly associated with male reproductive problems commonly associated with the alteration of sperm parameters as...
BACKGROUND
Testicular germ cell tumor such as seminoma is strongly associated with male reproductive problems commonly associated with the alteration of sperm parameters as described in testicular dysgenesis syndrome. Interestingly, numerous studies have reported that the precursor of germ cell cancer, germ cell neoplasia in situ (GCNIS), present similarities to fetal gonocytes, specifically characterized by global DNA hypomethylation particularly on imprinting sequences. These disorders may have a common origin derived from perturbations of embryonal programming during fetal development. Presently, there is no available information concerning the sperm DNA methylation patterns of testicular cancer patients. For the first time, we evaluated the sperm imprinting of seminoma patients. A total of 92 cryopreserved sperm samples were included, 31 before seminoma treatment (S): 23 normozoospermic (SN) and 8 oligozoospermic (SO) and 61 sperm controls samples: 31 normozoospermic (N) and 30 oligozoospermic (O). DNA methylation levels of seven differentially methylated regions (DMRs) of imprinted genes [H19/IGF2: IG-DMR (CTCF3 and CTCF6 of H19 gene); IGF2-DMRs (DMR0 and DMR2); MEG3/DLK1:IG-DMR; SNURF:TSS-DMR; KCNQ1OT1:TSS-DMR] were assessed by pyrosequencing. All comparative analyses were adjusted for age.
RESULTS
Comparisons of sperm DNA methylation levels between seminoma (S) and normozoospermic (N) samples showed a significant difference for the SNURF sequence (p = 0.017), but after taking into account the sperm parameters, no difference was observed. However, we confirmed a significant association between oligozoospermia (O) and imprinting defects for H19/IGF2-CTCF6 (p = 0.001), MEG3/DLK1 (p = 0.017), IGF2-DMR2 (p = 0.022), and SNURF (p = 0.032) in comparison with control groups (N).
CONCLUSIONS
This study highlights the high risk of sperm imprinting defects in cases of oligozoospermia and shows for the first time that seminoma patients with normal spermatogenesis present sperm imprinting integrity. These data suggest a low probability of the involvement of a common imprinting defect in fetal cells leading to both TGCT and subfertility.
Topics: Adult; Calcium-Binding Proteins; Genomic Imprinting; Humans; Insulin-Like Growth Factor II; Intercellular Signaling Peptides and Proteins; Male; Membrane Proteins; Middle Aged; Nuclear Proteins; Oligospermia; RNA, Long Noncoding; Seminoma; Sequence Analysis, DNA; Spermatozoa; Testicular Neoplasms
PubMed: 30340650
DOI: 10.1186/s13148-018-0559-z -
Journal of Reproduction & Infertility 2021Male infertility is associated with altered characteristics of the sperm within the ejaculate. It is possible to find molecular explanations for the observed phenotypes...
BACKGROUND
Male infertility is associated with altered characteristics of the sperm within the ejaculate. It is possible to find molecular explanations for the observed phenotypes and their consequences. This study aimed to analyze, using a specialized software, a gene set of transcriptomic data from different types of ejaculates.
METHODS
Data from ejaculate samples categorized as normal, oligospermia, and teratozoospermia were obtained from Gene Expression Omnibus (GEO). After normalization, the data average for each sample category was calculated and analyzed independently using Ingenuity Pathway Analysis (IPA).
RESULTS
Five important canonical pathways are involved in normal and altered semen samples (Oligospermia and teratozoospermia) except sirtuin signaling and mitochondrial dysfunction pathways. The five most important biological processes are identified in all semen phenotypes, but the only difference is the genes connected with initiation of RNA transcription in oligospermic and asthenospermic samples.
CONCLUSION
Surprisingly, different types of ejaculates share many pathways and biological processes; sperm proteomics as a new global approach gives clues for the development of strategies to explain the reason for observed phenotypes of ejaculated spermatozoa, their possible effect on fertility, and for implementing research strategies in the context of infertility diagnosis and treatment.
PubMed: 34900641
DOI: 10.18502/jri.v22i3.6721