scholarly journals Novel Mutations in X-Linked, USP26-Induced Asthenoteratozoospermia and Male Infertility

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1594
Author(s):  
Chunyu Liu ◽  
Ying Shen ◽  
Qunshan Shen ◽  
Wen Zhang ◽  
Jiaxiong Wang ◽  
...  
Keyword(s):  
Male Infertility ◽  
Deubiquitinating Enzyme ◽  
Linked Gene ◽  
Real Time Quantitative Pcr ◽  
Infertile Men ◽  
Normal Sperm ◽  
Abnormal Sperm ◽  
Whole Exome ◽  
Reproductive Counseling ◽  
Hematoxylin Eosin

Male infertility is a multifactorial disease with a strong genetic background. Abnormal sperm morphologies have been found to be closely related to male infertility. Here, we conducted whole-exome sequencing in a cohort of 150 Han Chinese men with asthenoteratozoospermia. Two novel hemizygous mutations were identified in USP26, an X-linked gene preferentially expressed in the testis and encoding a deubiquitinating enzyme. These USP26 variants are extremely rare in human population genome databases and have been predicted to be deleterious by multiple bioinformatics tools. Hematoxylin-eosin staining and electron microscopy analyses of the spermatozoa from men harboring hemizygous USP26 variants showed a highly aberrant morphology and ultrastructure of the sperm heads and flagella. Real-time quantitative PCR and immunoblotting assays revealed obviously reduced levels of USP26 mRNA and protein in the spermatozoa from men harboring hemizygous deleterious variants of USP26. Furthermore, intracytoplasmic sperm injections performed on infertile men harboring hemizygous USP26 variants achieved satisfactory outcomes. Overall, our study demonstrates that USP26 is essential for normal sperm morphogenesis, and hemizygous USP26 mutations can induce X-linked asthenoteratozoospermia. These findings will provide effective guidance for the genetic and reproductive counseling of infertile men with asthenoteratozoospermia.

scholarly journals The possible association of clusterin fucosylation changes with male fertility disorders

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ewa Janiszewska ◽  
Izabela Kokot ◽  
Iwona Gilowska ◽  
Ricardo Faundez ◽  
Ewa Maria Kratz
Keyword(s):  
Male Infertility ◽  
Blood Serum ◽  
Seminal Plasma ◽  
Male Fertility ◽  
Sperm Count ◽  
Semen Analysis ◽  
Infertile Men ◽  
Abnormal Sperm ◽  
Fertility Disorders ◽  
Oligosaccharide Structures

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.

The influence of Robertsonian translocations on semen parameters

2020 ◽  
pp. 87-88
Author(s):  
М.В. Андреева ◽  
М.И. Штаут ◽  
Т.М. Сорокина ◽  
Л.Ф. Курило ◽  
В.Б. Черных
Keyword(s):  
Male Infertility ◽  
Semen Parameters ◽  
Meiotic Arrest ◽  
Robertsonian Translocations ◽  
Prophase I ◽  
Infertile Men ◽  
Fertility Problems ◽  
Spermatogenesis Impairment

Обследованы 19 мужчин с нарушением фертильности, носителей транслокаций rob(13;14) и rob(13;15). Показано, что нарушение репродуктивной функции обусловлено блоком сперматогенеза в профазе I мейоза, приводящего к азооспермии или олигоастенотератозооспермии и мужскому бесплодию. We examined 19 infertile men, carriers of translocations rob (13;14) and rob (13;15). We assume that fertility problems are resulted from spermatogenesis impairment because of meiotic arrest at prophase I stages, that leads to azoospermia or oligoastenoteratozoospermia and male infertility.

scholarly journals Idiopathic Infertility as a Feature of Genome Instability

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 628
Author(s):  
Agrita Puzuka ◽  
Baiba Alksere ◽  
Linda Gailite ◽  
Juris Erenpreiss
Keyword(s):  
Life Expectancy ◽  
Male Infertility ◽  
Genome Instability ◽  
Repair System ◽  
Environmental Aspects ◽  
Strand Breaks ◽  
Testicular Dysfunction ◽  
Infertile Men ◽  
Dna Strand ◽  
Dynamic Mutations

Genome instability may play a role in severe cases of male infertility, with disrupted spermatogenesis being just one manifestation of decreased general health and increased morbidity. Here, we review the data on the association of male infertility with genetic, epigenetic, and environmental alterations, the causes and consequences, and the methods for assessment of genome instability. Male infertility research has provided evidence that spermatogenic defects are often not limited to testicular dysfunction. An increased incidence of urogenital disorders and several types of cancer, as well as overall reduced health (manifested by decreased life expectancy and increased morbidity) have been reported in infertile men. The pathophysiological link between decreased life expectancy and male infertility supports the notion of male infertility being a systemic rather than an isolated condition. It is driven by the accumulation of DNA strand breaks and premature cellular senescence. We have presented extensive data supporting the notion that genome instability can lead to severe male infertility termed “idiopathic oligo-astheno-teratozoospermia.” We have detailed that genome instability in men with oligo-astheno-teratozoospermia (OAT) might depend on several genetic and epigenetic factors such as chromosomal heterogeneity, aneuploidy, micronucleation, dynamic mutations, RT, PIWI/piRNA regulatory pathway, pathogenic allelic variants in repair system genes, DNA methylation, environmental aspects, and lifestyle factors.

scholarly journals Variations in Antioxidant Genes and Male Infertility

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Bolan Yu ◽  
Zhaofeng Huang
Keyword(s):  
Male Infertility ◽  
Population Studies ◽  
Sperm Quality ◽  
Synergistic Effects ◽  
Related Factor ◽  
Antioxidant Genes ◽  
Functional Polymorphisms ◽  
Normal Sperm ◽  
Oxide Synthase ◽  
Defective Spermatogenesis

Oxidative stress and reactive oxygen species (ROS) are generated from both endogenous and environmental resources, which in turn may cause defective spermatogenesis and male infertility. Antioxidant genes, which include catalase (CAT), glutathione peroxidase (GPX), glutathioneS-transferase (GST), nitric oxide synthase (NOS), nuclear factor erythroid 2-related factor 2 (NRF2), and superoxide dismutase (SOD), play important roles in spermatogenesis and normal sperm function. In this review, we discuss the association between variations in major antioxidant genes and male infertility. Numerous studies have suggested that genetic disruption or functional polymorphisms in these antioxidant genes are associated with a higher risk for male infertility, which include low sperm quality, oligoasthenoteratozoospermia, oligozoospermia, and subfertility. The synergistic effects of environmental ROS and functional polymorphisms on antioxidant genes that result in male infertility have also been reported. Therefore, variants in antioxidant genes, which independently or synergistically occur with environmental ROS, affect spermatogenesis and contribute to the occurrence of male infertility. Large cohort and multiple center-based population studies to identify new antioxidant genetic variants that increase susceptibility to male infertility as well as validate its potential as genetic markers for diagnosis and risk assessment for male infertility for precise clinical approaches are warranted.

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

2014 ◽  
Vol 86 (3) ◽  
pp. 164 ◽  
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.

scholarly journals Comparison of semen characteristics between indigenous and Amo breeds cockerel of Gombe State, Nigeria

2019 ◽  
Vol 15 (2-1) ◽  
pp. 303-306
Author(s):  
Tijjani Haruna Usman ◽  
Saleh Mohammed Sir ◽  
Ma’aruf Bashir Sani
Keyword(s):  
Semen Quality ◽  
Sperm Concentration ◽  
Progressive Motility ◽  
Indigenous Breed ◽  
Normal Sperm ◽  
Abnormal Sperm ◽  
Significant Difference ◽  
Semen Characteristics ◽  
Genetically Improved ◽  
Abdominal Massage

The experiment was carried out to compare the semen characteristics of indigenous and Amo strains of cockerel at poultry unit of teaching and research farm of Federal University of Kashere, Gombe State, Nigeria. Semen samples were collected from nine indigenous and nine Amo breeds of cockerel at three days interval for two weeks using abdominal massage technique. Semen samples were examined macroscopically for semen colour, pH and ejaculation volume. Then, microscopic observation was carried for sperm concentration, mass motility, progressive motility, live and dead sperms percentage, normal and abnormal sperm, all for semen characteristics. The results showed a significant difference (P ≤ 0.05) between mass motility, progressive motility, sperm concentration and head defects of 4.85 ± 0.27 to 4.37 ± 0.19, 95.13 ± 0.43 to 81.63 ± 1.15%, 4.93 ± 1.84 to 3.40 ± 1.07×109/ml and 2.96 ± 0.17 to 3.44 ± 0.12% for indigenous and Amo breeds of cockerel, respectively. There were no significant differences observed as semen colour, ejaculate volume, semen pH, live / dead normal sperm neck (mid-piece), tail defects and sperm total abnormalities were found to be 2.85 ± 0.07 to 2.00 ± 0.090.21 ± 0.17 to 0.20 ± 0.02 /ml, 88.85 ± 0.58 to 72.70 ± 0.54% /ml, 11.14 ± 0.58 to 27.29 ± 0.54%, 81.00 ± 0.78 to 66.22 ± 0.61%,9.03 ± 0.42 to 13.96 ± 0.47%, 9.70 ±  to 13.00 ± 0.30 and 21.70 ± 0.59 to 30.40 ± 0.53% for the indigenous and Amo breed groups of cockerel, respectively. It was concluded that semen quality characteristics could be differed between genetically improved (Amo strain) and indigenous breed of cockerels.

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

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.

scholarly journals Sperm Proteome Analysis and Identification of Fertility-Associated Biomarkers in Unexplained Male Infertility

Genes ◽  
2019 ◽  
Vol 10 (7) ◽  
pp. 522 ◽  
Author(s):  
Selvam ◽  
Agarwal ◽  
Pushparaj ◽  
Baskaran ◽  
Bendou
Keyword(s):  
Male Infertility ◽  
Radical Scavenging ◽  
Surface Protein ◽  
Proteome Analysis ◽  
Fold Change ◽  
Semen Parameters ◽  
Proteomic Profiling ◽  
Altered Expression ◽  
Fertilization Process ◽  
Infertile Men

Up to 30% of men with normal semen parameters suffer from infertility and the reason for this is unknown. Altered expression of sperm proteins may be a major cause of infertility in these men. Proteomic profiling was performed on pooled semen samples from eight normozoospermic fertile men and nine normozoospermic infertile men using LC-MS/MS. Furthermore, key differentially expressed proteins (DEPs) related to the fertilization process were selected for validation using Western blotting. A total of 1139 and 1095 proteins were identified in normozoospermic fertile and infertile men, respectively. Of these, 162 proteins were identified as DEPs. The canonical pathway related to free radical scavenging was enriched with upregulated DEPs in normozoospermic infertile men. The proteins associated with reproductive system development and function, and the ubiquitination pathway were underexpressed in normozoospermic infertile men. Western blot analysis revealed the overexpression of annexin A2 (ANXA2) (2.03 fold change; P = 0.0243), and underexpression of sperm surface protein Sp17 (SPA17) (0.37 fold change; P = 0.0205) and serine protease inhibitor (SERPINA5) (0.32 fold change; P = 0.0073) in men with unexplained male infertility (UMI). The global proteomic profile of normozoospermic infertile men is different from that of normozoospermic fertile men. Our data suggests that SPA17, ANXA2, and SERPINA5 may potentially serve as non-invasive protein biomarkers associated with the fertilization process of the spermatozoa in UMI.

scholarly journals Haploid male germ cells—the Grand Central Station of protein transport

2020 ◽  
Vol 26 (4) ◽  
pp. 474-500 ◽  
Author(s):  
Christiane Pleuger ◽  
Mari S Lehti ◽  
Jessica EM Dunleavy ◽  
Daniela Fietz ◽  
Moira K O’Bryan
Keyword(s):  
Male Infertility ◽  
Protein Transport ◽  
Model System ◽  
Sperm Head ◽  
Vesicle Transport ◽  
Future Research ◽  
Significant Percentage ◽  
Human Male ◽  
Abnormal Sperm ◽  
Haploid Male

Abstract BACKGROUND The precise movement of proteins and vesicles is an essential ability for all eukaryotic cells. Nowhere is this more evident than during the remarkable transformation that occurs in spermiogenesis—the transformation of haploid round spermatids into sperm. These transformations are critically dependent upon both the microtubule and the actin cytoskeleton, and defects in these processes are thought to underpin a significant percentage of human male infertility. OBJECTIVE AND RATIONALE This review is aimed at summarising and synthesising the current state of knowledge around protein/vesicle transport during haploid male germ cell development and identifying knowledge gaps and challenges for future research. To achieve this, we summarise the key discoveries related to protein transport using the mouse as a model system. Where relevant, we anchored these insights to knowledge in the field of human spermiogenesis and the causality of human male infertility. SEARCH METHODS Relevant studies published in English were identified using PubMed using a range of search terms related to the core focus of the review—protein/vesicle transport, intra-flagellar transport, intra-manchette transport, Golgi, acrosome, manchette, axoneme, outer dense fibres and fibrous sheath. Searches were not restricted to a particular time frame or species although the emphasis within the review is on mammalian spermiogenesis. OUTCOMES Spermiogenesis is the final phase of sperm development. It results in the transformation of a round cell into a highly polarised sperm with the capacity for fertility. It is critically dependent on the cytoskeleton and its ability to transport protein complexes and vesicles over long distances and often between distinct cytoplasmic compartments. The development of the acrosome covering the sperm head, the sperm tail within the ciliary lobe, the manchette and its role in sperm head shaping and protein transport into the tail, and the assembly of mitochondria into the mid-piece of sperm, may all be viewed as a series of overlapping and interconnected train tracks. Defects in this redistribution network lead to male infertility characterised by abnormal sperm morphology (teratozoospermia) and/or abnormal sperm motility (asthenozoospermia) and are likely to be causal of, or contribute to, a significant percentage of human male infertility. WIDER IMPLICATIONS A greater understanding of the mechanisms of protein transport in spermiogenesis offers the potential to precisely diagnose cases of male infertility and to forecast implications for children conceived using gametes containing these mutations. The manipulation of these processes will offer opportunities for male-based contraceptive development. Further, as increasingly evidenced in the literature, we believe that the continuous and spatiotemporally restrained nature of spermiogenesis provides an outstanding model system to identify, and de-code, cytoskeletal elements and transport mechanisms of relevance to multiple tissues.

scholarly journals Novel DNAAF6 variants identified by whole-exome sequencing cause male infertility and primary ciliary dyskinesia

2020 ◽  
Vol 37 (4) ◽  
pp. 811-820 ◽  
Author(s):  
Ying Wang ◽  
Chaofeng Tu ◽  
Hongchuan Nie ◽  
Lanlan Meng ◽  
Dongyan Li ◽  
...  
Keyword(s):  
Male Infertility ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Primary Ciliary Dyskinesia ◽  
Whole Exome ◽  
Ciliary Dyskinesia
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