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Genes May 2024Several genes are implicated in spermatogenesis and fertility regulation, and these genes are presently being analysed in clinical practice due to their involvement in... (Review)
Review
Several genes are implicated in spermatogenesis and fertility regulation, and these genes are presently being analysed in clinical practice due to their involvement in male factor infertility (MFI). However, there are still few genetic analyses that are currently recommended for use in clinical practice. In this manuscript, we reviewed the genetic causes of qualitative sperm defects. We distinguished between alterations causing reduced sperm motility (asthenozoospermia) and alterations causing changes in the typical morphology of sperm (teratozoospermia). In detail, the genetic causes of reduced sperm motility may be found in the alteration of genes associated with sperm mitochondrial DNA, mitochondrial proteins, ion transport and channels, and flagellar proteins. On the other hand, the genetic causes of changes in typical sperm morphology are related to conditions with a strong genetic basis, such as macrozoospermia, globozoospermia, and acephalic spermatozoa syndrome. We tried to distinguish alterations approved for routine clinical application from those still unsupported by adequate clinical studies. The most important aspect of the study was related to the correct identification of subjects to be tested and the correct application of genetic tests based on clear clinical data. The correct application of available genetic tests in a scenario where reduced sperm motility and changes in sperm morphology have been observed enables the delivery of a defined diagnosis and plays an important role in clinical decision-making. Finally, clarifying the genetic causes of MFI might, in future, contribute to reducing the proportion of so-called idiopathic MFI, which might indeed be defined as a subtype of MFI whose cause has not yet been revealed.
Topics: Humans; Male; Spermatozoa; Sperm Motility; Asthenozoospermia; Infertility, Male; Teratozoospermia; DNA, Mitochondrial; Genetic Testing
PubMed: 38790229
DOI: 10.3390/genes15050600 -
Frontiers in Genetics 2023Asthenozoospermia (AZS) is one of the most common causes of male fertility, affecting family wellbeing and population growth. Chronic epididymitis (CE) is a common and...
Asthenozoospermia (AZS) is one of the most common causes of male fertility, affecting family wellbeing and population growth. Chronic epididymitis (CE) is a common and lingering inflammatory disease in the scrotum. Inflammation in the epididymis has a severe impact on sperm motility. This study aimed to explore the genetic profile and critical pathways involved in the pathological mechanisms of AZS and CE, and discover potential biomarkers. Genomic datasets of AZS and CE were obtained from the Gene Expression Omnibus (GEO) database, and relevant differentially expressed genes (DEGs) were identified. GO and pathway enrichment analyses, construction of a protein-protein interaction network, and receiver operator characteristic curve analysis were conducted. The expression profile of hub genes was validated in immunohistochemical data and testicular cell data. Immune infiltration, miRNA-hub gene interactions, and gene-disease interactions were explored. The mRNA levels of hub genes were further measured by qRT-PCR. A total of 109 DEGs were identified between the AZS/CE and healthy control groups. Pathways of the immune system, neutrophil degranulation, and interleukin-4 and interleukin-13 signaling were enriched in AZS and CE. Five hub genes ( and ) were selected, and their diagnostic values were validated in AZS, CE, and independent validation sets (area under the curve >0.7). Furthermore, the five-hub gene signature was well characterized in testicular immunohistochemical staining and testicular cells from healthy controls. Immune infiltration analysis showed that infiltration of CD8 cells and T helper cells was significantly related to the expression level of five hub genes. In addition, a miRNA-hub gene network and interaction of other diseases were displayed. The mRNA levels of hub genes ( and ) were significantly elevated in the patient group. The mRNA level of CTSK also showed a similar trend. Our study uncovered the genetic profile involved in AZS and CE, and elucidated enriched pathways and molecular associations between hub genes and immune infiltration. This finding provides novel insight into the common pathogenesis of both diseases as well as the potential biomarkers for CE-associated AZS.
PubMed: 37152990
DOI: 10.3389/fgene.2023.1110218 -
International Journal of Molecular... Sep 2020Infertility has become a global health issue, with approximately 50% of infertility cases generated by disorders in male reproduction. Spermatozoa are conveyed towards... (Review)
Review
Infertility has become a global health issue, with approximately 50% of infertility cases generated by disorders in male reproduction. Spermatozoa are conveyed towards female genital tracts in a safe surrounding provided by the seminal plasma. Interestingly, this dynamically changing medium is a rich source of proteins, essential not only for sperm transport, but also for its protection and maturation. Most of the seminal proteins are acquired by spermatozoa in transit through exosomes (epididymosomes and prostasomes). The high number of seminal proteins, the increasing knowledge of their origins and biological functions and their differential expression in the case of azoospermia, asthenozoospermia, oligozoospermia and teratozoospermia or other conditions of male infertility have allowed the identification of a wide variety of biomarker candidates and their involvement in biological pathways, thus to strongly suggest that the proteomic landscape of seminal plasma may be a potential indicator of sperm dysfunction. This review summarizes the current knowledge in seminal plasma proteomics and its potentiality as a diagnostic tool in different degrees of male infertility.
Topics: Biomarkers; Exosomes; Humans; Infertility, Male; Male; Proteome; Semen; Spermatozoa
PubMed: 32987677
DOI: 10.3390/ijms21197022 -
Genes Jul 2022Asthenozoospermia is one of the main causes of male infertility and it is characterized by reduced sperm motility. Several mutations in genes that code for structural or...
Asthenozoospermia is one of the main causes of male infertility and it is characterized by reduced sperm motility. Several mutations in genes that code for structural or functional constituents of the sperm have already been identified as known causes of asthenozoospermia. In contrast, the role of sperm RNA in regulating sperm motility is still not fully understood. Consequently, here we aim to contribute to the knowledge regarding the expression of sperm RNA, and ultimately, to provide further insights into its relationship with sperm motility. We investigated the expression of a group of mRNAs by using real-time PCR (, , , , , , , , and ) and the highest score corresponding to the target miRNA for each mRNA in asthenozoospermic and normozoospermic individuals. We observed a reduced expression of all mRNAs and miRNAs in asthenozoospermic patients compared to controls, with a more accentuated reduction in patients with progressive sperm motility lower than 15%. Our work provides further insights regarding the role of RNA in regulating sperm motility. Further studies are required to determine how these genes and their corresponding miRNA act regarding sperm motility, particularly and , which have not previously been seen to play a significant role in regulating sperm motility.
Topics: Asthenozoospermia; Humans; Ion Channels; Male; MicroRNAs; RNA, Messenger; Semen; Sperm Motility; Spermatozoa
PubMed: 35886074
DOI: 10.3390/genes13071291 -
International Journal of Molecular... Mar 2023To evaluate whether the follicle-stimulating hormone (FSH) receptor (FSHR) is expressed in human spermatozoa and the effects of FSH incubation on sperm function....
To evaluate whether the follicle-stimulating hormone (FSH) receptor (FSHR) is expressed in human spermatozoa and the effects of FSH incubation on sperm function. Twenty-four Caucasian men were recruited. Thirteen patients had asthenozoospermia, and the remaining 11 had normal sperm parameters (controls). After confirming FSHR expression, spermatozoa from patients and controls were incubated with increasing concentrations of human purified FSH (hpFSH) to reassess FSHR expression and localization and to evaluate progressive and total sperm motility, the mitochondrial membrane potential, and protein kinase B (AKT) 473 and 308 phosphorylation. FSHR is expressed in the post-acrosomal segment, neck, midpiece, and tail of human spermatozoa. Its localization does not differ between patients and controls. Incubation with hpFSH at a concentration of 30 mIU/mL appeared to increase FSHR expression mainly in patients. Incubation of human spermatozoa with hpFSH overall resulted in an overall deterioration of both progressive and total motility in patients and controls and worse mitochondrial function only in controls. Finally, incubation with FSH increased AKT/tubulin phosphorylation to a greater extent than AKT. FSHR is expressed in the post-acrosomal region, neck, midpiece, and tail of human spermatozoa. Contrary to a previous study, we report a negative effect of FSH on sperm motility and mitochondrial function. FSH also activates the AKT signaling pathway.
Topics: Humans; Male; Follicle Stimulating Hormone; Proto-Oncogene Proteins c-akt; Sperm Motility; Semen; Follicle Stimulating Hormone, Human; Receptors, FSH; Spermatozoa
PubMed: 37047508
DOI: 10.3390/ijms24076536 -
JBRA Assisted Reproduction Jun 2024Infertility is a widespread global issue that affects approximately 15% of sexually active and active couples, which contributes to about 50% of cases. Currently, the... (Review)
Review
Infertility is a widespread global issue that affects approximately 15% of sexually active and active couples, which contributes to about 50% of cases. Currently, the condition remains prevalent and often inadequately treated. This systematic review aims to evaluate existing studies investigating the effects of probiotic supplementation in men. A comprehensive search was conducted across major databases, including PubMed, Cochrane, Science Direct, and Scielo, using relevant keywords such as 'probiotic' OR 'Lactobacillus' OR 'Bifidobacterium' AND 'Male infertility' OR 'male fertility' OR 'sperm quality' OR 'sperm motility' OR 'oligoasthenoteratozoospermia' and their Portuguese equivalents. Four randomized clinical studies met the inclusion criteria, focusing on men diagnosed with idiopathic male infertility (oligozoospermia, teratozoospermia, and asthenozoospermia). The findings revealed that probiotic administration exhibited promising antioxidant properties by combating reactive oxygen species (ROS), consequently protecting sperm DNA from damage that correlates with declining sperm quality. Significant improvements were observed across all sperm parameters, with notable enhancement in motility. Consequently, probiotic supplementation emerges as a potential therapeutic alternative for men diagnosed with idiopathic infertility, demonstrating positive effects on sperm quality.
Topics: Humans; Male; Probiotics; Infertility, Male; Dietary Supplements; Sperm Motility
PubMed: 38530761
DOI: 10.5935/1518-0557.20240013 -
Qatar Medical Journal 2021Infertility is defined as the inability of heterosexual couples to achieve a successful clinically recognizable pregnancy after 12 months or more of regular, unprotected...
BACKGROUND/AIM
Infertility is defined as the inability of heterosexual couples to achieve a successful clinically recognizable pregnancy after 12 months or more of regular, unprotected sexual intercourse. Infertility estimations are very important to inform the healthcare policymakers and governments to implement appropriate social and economic policies. Thus, this study aimed to estimate the pooled prevalence of infertility (primary and secondary) and its etiologic factors in Sudan.
METHODS
This study included all published and unpublished studies written in Arabic or English. Electronic sources (namely, PubMed, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov) and nonelectronic sources (direct Google search, Google Scholar, OpenGrey, OATD, WorldCat log, and university websites) were used from their inception to May 16, 2021. A total of 1955 studies were reviewed, of which only 20 studies were eligible for the meta-analysis. Studies were eligible if they provided the prevalence of infertility in Sudan. The Joanna Briggs Institute Quality Assessment Tool was used to evaluate each study. Data synthesis and statistical analysis were conducted using Jeffrey's Amazing Statistics Program version 0.14.1.0.
RESULTS
The pooled prevalence of overall infertility, primary infertility, and secondary infertility in Sudan were 13% (I = 96.45, < 0.001), 65% (I = 98.5, < 0.001), and 35% (I = 98.5, < 0.001), respectively, and the prevalence of infertility factors were 41%, 27%, 16%, and 17% for female, male, combined factors, and unexplained factors, respectively. Women with infertility were mainly present because of ovulatory disorders (ovulatory factors, 36%; polycystic ovary syndrome, 38%). By contrast, spermatic disorders such as azoospermia (37%), oligozoospermia (30%), and asthenozoospermia (30%) were the main causes of male infertility.
CONCLUSION
In Sudan, the prevalence of primary infertility is higher than that of secondary infertility. Female factors were the most common causes of infertility in Sudan, and this study found a high prevalence of unexplained factors. Polycystic ovary syndrome and azoospermia were the most common causes of female and male infertility in Sudan, respectively. The interpretation of these findings should take into consideration the presence of substantial heterogeneity between the included studies.
PubMed: 34650907
DOI: 10.5339/qmj.2021.47 -
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 -
Asian Journal of Andrology 2021The novel coronavirus disease (COVID-19) pandemic is emerging as a global health threat and shows a higher risk for men than women. Thus far, the studies on andrological...
The novel coronavirus disease (COVID-19) pandemic is emerging as a global health threat and shows a higher risk for men than women. Thus far, the studies on andrological consequences of COVID-19 are limited. To ascertain the consequences of COVID-19 on sperm parameters after recovery, we recruited 41 reproductive-aged male patients who had recovered from COVID-19, and analyzed their semen parameters and serum sex hormones at a median time of 56 days after hospital discharge. For longitudinal analysis, a second sampling was obtained from 22 of the 41 patients after a median time interval of 29 days from first sampling. Compared with controls who had not suffered from COVID-19, the total sperm count, sperm concentration, and percentages of motile and progressively motile spermatozoa in the patients were significantly lower at first sampling, while sperm vitality and morphology were not affected. The total sperm count, sperm concentration, and number of motile spermatozoa per ejaculate were significantly increased and the percentage of morphologically abnormal sperm was reduced at the second sampling compared with those at first in the 22 patients examined. Though there were higher prolactin and lower progesterone levels in patients at first sampling than those in controls, no significant alterations were detected for any sex hormones examined over time following COVID-19 recovery in the 22 patients. Although it should be interpreted carefully, these findings indicate an adverse but potentially reversible consequence of COVID-19 on sperm quality.
Topics: Adult; Asthenozoospermia; COVID-19; China; Gonadal Steroid Hormones; Humans; Male; Progesterone; Prolactin; SARS-CoV-2; Semen; Semen Analysis; Sperm Count; Sperm Motility; Spermatozoa; Time Factors
PubMed: 33975987
DOI: 10.4103/aja.aja_31_21 -
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