Male ; Humans ; Avena ; Infertility, Male/genetics* ; Oligospermia/genetics* ; Asthenozoospermia ; Spermatozoa

Male infertility is a worldwide problem, and about 15% of the cases are associated with spermatogenesis-related gene mutation. The mammalian gene UBE2B is the homolog of the RAD6 gene of yeast, belonging to the ubiquitin proteasome system and playing an important role in spermatogenesis. Mice lacking the UBE2B gene are infertile, with reduced sperm motility, increased morphologically abnormal sperm, and inhibited meiosis of spermatogonia. Accumulated evidence shows that UBE2B gene mutants and single nucleotide polymorphisms are associated with male infertility. This article reviews the relation between the UBE2B gene and male infertility, offering some theoretical evidence for the diagnosis and treatment of male infertility.
Animals ; Asthenozoospermia ; genetics ; Humans ; Infertility, Male ; genetics ; Male ; Meiosis ; Mice ; Mutation ; Polymorphism, Single Nucleotide ; Spermatogenesis ; genetics ; Ubiquitin-Conjugating Enzymes ; genetics

Primary ciliary dyskinesia (PCD) is a rare hereditary orphan condition that results in variable phenotypes, including infertility. About 50 gene variants are reported in the scientific literature to cause PCD, and among them, dynein axonemal assembly factor 4 ( DNAAF4 ) has been recently reported. DNAAF4 has been implicated in the preassembly of a multiunit dynein protein essential for the normal function of locomotory cilia as well as flagella. In the current study, a single patient belonging to a Chinese family was recruited, having been diagnosed with PCD and asthenoteratozoospermia. The affected individual was a 32-year-old male from a nonconsanguineous family. He also had abnormal spine structure and spinal cord bends at angles diagnosed with scoliosis. Medical reports, laboratory results, and imaging data were investigated. Whole-exome sequencing, Sanger sequencing, immunofluorescence analysis, hematoxylin-eosin staining, and in silico functional analysis, including protein modeling and docking studies, were used. The results identified DNAAF4 disease-related variants and confirmed their pathogenicity. Genetic analysis through whole-exome sequencing identified two pathogenic biallelic variants in the affected individual. The identified variants were a hemizygous splice site c.784-1G>A and heterozygous 20.1 Kb deletion at the DNAAF4 locus, resulting in a truncated and functionless DNAAF4 protein. Immunofluorescence analysis indicated that the inner dynein arm was not present in the sperm flagellum, and sperm morphological analysis revealed small sperm with twisted and curved flagella or lacking flagella. The current study found novel biallelic variants causing PCD and asthenoteratozoospermia, extending the range of DNAAF4 pathogenic variants in PCD and associated with the etiology of asthenoteratozoospermia. These findings will improve our understanding of the etiology of PCD.
Adult ; Humans ; Male ; Asthenozoospermia/genetics* ; Dyneins/genetics* ; East Asian People ; Kartagener Syndrome/genetics* ; Mutation ; Proteins/genetics* ; Semen/metabolism*

Asthenoteratozoospermia is one of the most severe types of qualitative sperm defects. Most cases are due to mutations in genes encoding the components of sperm flagella, which have an ultrastructure similar to that of motile cilia. Coiled-coil domain containing 103 (CCDC103) is an outer dynein arm assembly factor, and pathogenic variants of CCDC103 cause primary ciliary dyskinesia (PCD). However, whether CCDC103 pathogenic variants cause severe asthenoteratozoospermia has yet to be determined. Whole-exome sequencing (WES) was performed for two individuals with nonsyndromic asthenoteratozoospermia in a consanguineous family. A homozygous CCDC103 variant segregating recessively with an infertility phenotype was identified (ENST00000035776.2, c.461A>C, p.His154Pro). CCDC103 p.His154Pro was previously reported as a high prevalence mutation causing PCD, though the reproductive phenotype of these PCD individuals is unknown. Transmission electron microscopy (TEM) of affected individuals' spermatozoa showed that the mid-piece was severely damaged with disorganized dynein arms, similar to the abnormal ultrastructure of respiratory ciliary of PCD individuals with the same mutation. Thus, our findings expand the phenotype spectrum of CCDC103 p.His154Pro as a novel pathogenic gene for nonsyndromic asthenospermia.
Asthenozoospermia/pathology* ; Dyneins/genetics* ; Homozygote ; Humans ; Male ; Microtubule-Associated Proteins ; Mutation ; Mutation, Missense ; Sperm Tail/metabolism*

OBJECTIVETo investigate the mRNA and protein expression levels of cysteine-rich secretory protein 2 (CRISP2) in the sperm of asthenospermia patients, and explore their relationship with sperm motility and related molecular mechanism.

METHODSWe collected 78 semen samples from adult male patients with asthenospermia and another 70 from healthy volunteers as controls. We extracted total RNA and total protein from the sperm following purification of the sperm by Percoll gradient centrifugation, and detected the relative expressions of CRISP2 mRNA and protein in the two groups by RT-PCR, SYBR Green real-time PCR and Western blot.

RESULTSThe expression of CRISP2 mRNA was down-regulated by 4.3 times and that of the CRISP2 protein by 1.71 times in the asthenospermia patients, significantly lower than in the normal control group (P < 0.05).

CONCLUSIONThe down-regulation of CRISP2 mRNA and protein expressions in the sperm of asthenospermia patients may be closely related with decreased sperm motility, which suggests that CRISP2 may serve as a potential molecular target for the research of asthenospermia.

Adult ; Asthenozoospermia ; genetics ; metabolism ; Case-Control Studies ; Glycoproteins ; genetics ; metabolism ; Humans ; Male ; Sperm Motility ; Spermatozoa ; metabolism ; physiology

OBJECTIVETo explore genetic etiologies of a patient with severe oligozoospermia and asthenozoospermia.

METHODSG-banded karyotyping and fluorescence in situ hybridization (FISH) were used to characterize the origin and structure of the abnormal chromosome discovered in this patient. Multiplex polymerase chain reaction (PCR) was used to detect microdeletion of azoospermia factor (AZF).

RESULTSG-banding revealed a karyotype of 45,X,der(15) (?::p11.2→ qter)dn for the patient. Dual-color FISH confirmed that SRY gene was present in a segment attached to the short arm of chromosome 15. Sex chromosome mosaicism and numerical abnormality therefore were both present. Dual-color FISH revealed karyotype of nuc ish(DXZ1× 1, SRY× 1)[390/400]/(DXZ1× 2, SRY× 1) [10/400]. Four-color FISH showed that the abnormal chromosome 15 has derived from a pseudodicentric (Y;15) translocation, and that the breakpoint on Y chromosome was located at Yq12. G-banding and FISH results confirmed that the karyotype was 45,X,der(15)(?::p11.2→ qter)dn.ish psu dic(15;Y)(p11.2;q12)(D15Z1+ , SNRPN+ , PML+ ; SRY+ , DYZ3+ , DYZ1+ ). Microdeletion of AZFc combined with sY254 deletion was detected by multiplex PCR.

CONCLUSIONCytogenetic and molecular genetic analysis of the patient has indicated meiotic disturbances with spermatogenetic arrest resulting from a pseudodicentric chromosome derived from Y;15 translocation and spermatogenesis dysfunction resulting from partial deletion of AZFc region.

Adult ; Asthenozoospermia ; diagnosis ; genetics ; Chromosomes, Human, Y ; Cytogenetics ; methods ; Humans ; Male ; Oligospermia ; diagnosis ; genetics ; Sex Chromosome Aberrations ; Translocation, Genetic

Asthenozoospermia ; genetics ; Azoospermia ; genetics ; Exons ; genetics ; Humans ; Infertility, Male ; genetics ; Male ; Polymerase Chain Reaction ; Receptors, Androgen ; genetics ; Slovenia ; Trinucleotide Repeat Expansion

OBJECTIVETo study the relationship between the expression of voltage-dependent Ca2+ channels (VDCCs) cal mRNA and asthenospermia.

METHODSBased on the WHO criteria, we filtered the donated semen by computer-aided sperm analysis (CASA), optimized the ejaculated sperm by discontinuous Percoll grads centrifugation, and examined and quantitated the multitype VDCCs alpha1 mRNA expressions in the sperm of normal men and asthenospermia patients using reverse transcription polymerase chain reaction (RT-PCR).

RESULTSCompared with the normal sperm, there were significant differences among the expressions of alpha1B (39.40 +/- 9.47), alpha1C (48.30 +/- 11.60), alpha1E (3.20 +/- 0.78), alpha1G (8.40 +/- 2.03) and alpha1H (5.70 +/- 1.47) mRNA messages in asthenospermia (P < 0.01).

CONCLUSIONThe abnormal expression of L-type and/or non-L-type VDCCs' mRNAs may be one of the causes of asthenospermia.

Asthenozoospermia ; genetics ; pathology ; Calcium Channels ; genetics ; Gene Expression ; Humans ; Male ; Protein Isoforms ; genetics ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Semen ; metabolism ; Sperm Motility ; genetics

One of the most common causes of male infertility is asthenospermia, whose pathogenesis, however, is not yet clear. Recent researches have found that some genes (such as tektin-2, DNAI1, DNAH5, DNAH11, AKAP4, SEPT4 and Smcp) and proteins (such as sperm proteins ACTB, ANXA5, PRM1, PRM2 and SABP and seminal proteins Tf, PSA, PAP and Fractalkine) are associated with asthenospermia. The finding of these molecular markers has provided a base for the explanation of the molecular mechanism of asthenospermia, and these markers may become the diagnostic and therapeutic targets of the disease.
A Kinase Anchor Proteins ; genetics ; Animals ; Asthenozoospermia ; genetics ; metabolism ; Cytoskeletal Proteins ; genetics ; DNA Methylation ; genetics ; GTP Phosphohydrolases ; genetics ; Humans ; Male ; Mutation ; Septins

OBJECTIVETo investigate the role of the TEKT4 protein in the pathogenesis of idiopathic asthenozoospermia.

METHODSWe separated and purified the ejaculated sperm from idiopathic asthenozoospermia patients and normozoospermic men by Percoll discontinuous density gradients, and detected the distribution and the expressions of TEKT4 mRNA and TEKT4 protein by RT-PCR and Western blot.

RESULTSRT-PCR revealed that the expression of TEKT4 mRNA was significantly lower in the sperm of the idiopathic asthenozoospermia patients than in those of the normozoospermic men (0.59 +/- 0.13 vs 0.75 +/- 0.15, t = 4.325, P < 0.05), and Western blot confirmed the results of RT-PCR (0.48 +/- 0.14 vs 0.69 +/- 0.13, t = 5.939, P < 0.05).

CONCLUSIONThe expression of TEKT4 is significantly decreased in the ejaculated sperm of idiopathic asthenozoospermia patients, which might be one of the causes of idiopathic asthenozoospermia.

Adult ; Asthenozoospermia ; metabolism ; Blotting, Western ; Case-Control Studies ; Cytoskeletal Proteins ; metabolism ; Humans ; Male ; RNA, Messenger ; genetics ; Sperm Motility ; Spermatozoa ; metabolism