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1.
Chinese Journal of Medical Genetics ; (6): 1068-1074, 2023.
Article in Chinese | WPRIM | ID: wpr-1009255

ABSTRACT

OBJECTIVE@#To explore the characteristics of copy number variation (CNV) within the Y chromosome azoospermia factor (AZF) region in patients with spermatogenesis disorders in the Shenzhen area.@*METHODS@#A total of 123 patients with spermatogenesis disorders who had visited Shenzhen People's Hospital from January 2016 to October 2022 (including 73 patients with azoospermia and 50 patients with oligozoospermia) and 100 normal semen males were selected as the study subjects. The AZF region was detected with multiplex ligation-dependent probe amplification (MLPA), and the correlation between the CNV in the AZF region and spermatogenesis disorders was analyzed using the chi-square test or Fisher's exact test.@*RESULTS@#19 CNV were detected among 53 patients from the 223 samples, including 20 cases (27.40%, 20/73) from the azoospermia group, 19 cases (38%, 19/50) from the oligozoospermia group, and 14 cases (14%, 14/100) from the normal control group. In the azoospermia, oligozoospermia, and normal control groups, the detection rates for CNV related to the AZFa region (including AZFab and AZFabc) were 5.48% (4/73), 2.00% (1/50), and 0 (0/100), respectively. The detection rates for the AZFb region (including the AZFbc region) were 6.85% (5/73), 0 (0/50), and 0 (0/100), respectively. The detection rates for gr/gr deletions in the AZFc region were 2.74% (2/73), 6.00% (3/50), and 9.00% (9/100), respectively, and those for b2/b4 deletions in the AZFc region were 2.74% (2/73), 10.00% (5/50), and 0 (0/100), respectively. The detection rates for complex rearrangements in the AZFc region were 6.85% (5/73), 18.00% (9/50), and 3.00% (3/100), respectively. Statistical analysis showed no significant difference in the detection rate of gr/gr deletions between the three groups (Fisher's Exact Test value = 2.712, P = 0.249); the differences in the detection rate of b2/b4 deletions between the three groups were statistically significant (Fisher's Exact Test value = 9.489, P = 0.002); the differences in the detection rate of complex rearrangements in the AZFc region between the three groups were statistically significant (Fisher's Exact Test value = 9.493, P = 0.006). In this study, a rare AZFa region ARSLP1 gene deletion (involving SY86 deletion) was detected in a patient with oligozoospermia.@*CONCLUSION@#CNV in the AZFa and AZFb regions have a severe impact on spermatogenesis, but partial deletion in the AZFa region (ARSLP1 gene deletion) has a minor impact on spermatogenesis. The b2/b4 deletion and complex rearrangement in the AZFc region may be risk factors for male infertility. The gr/gr deletion may not serve as a risk factor for male infertility in the Shenzhen area.


Subject(s)
Humans , Male , Azoospermia/genetics , DNA Copy Number Variations , Oligospermia/genetics , Infertility, Male/genetics , Y Chromosome
2.
Asian Journal of Andrology ; (6): 404-409, 2023.
Article in English | WPRIM | ID: wpr-981951

ABSTRACT

Male infertility caused by idiopathic oligoasthenospermia (OAT) is known as idiopathic male infertility. Glutathione S-transferase (GST) and fluoride may play important roles in idiopathic male infertility, but their effects are still unknown. Our study examined the relationship between GST polymorphisms and fluoride-induced toxicity in idiopathic male infertility and determined the underlying mechanism. Sperm, blood, and urine samples were collected from 560 males. Fluoride levels were measured by a highly selective electrode method, and GST genotypes were identified using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Semen parameters, DNA fragmentation index (DFI), mitochondrial membrane potential (MMP), and oxidative stress (OS) biomarkers were statistically assessed at the P < 0.05 level. Compared with healthy fertile group, semen parameters, fluoride levels, OS biomarkers, sex hormone levels, and MMP and DFI levels were lower in the idiopathic male infertility group. For glutathione S-transferase M1 (GSTM1[-]) and glutathione S-transferase T1 (GSTT1[-]) or glutathione S-transferase P1 (GSTP1) mutant genotypes, levels of semen fluoride, OS, MMP, and DFI were considerably higher, and the mean levels of sperm parameters and testosterone were statistically significant in GSTM1(+), GSTT1(+), and GSTP1 wild-type genotypes. Both semen and blood fluoride levels were associated with oxidative stress in idiopathic male infertility patients. Elevated fluoride in semen with the genotypes listed above was linked to reproductive quality in idiopathic male infertility patients. In conclusion, GST polymorphisms and fluorine may have an indicative relationship between reproductive quality and sex hormone levels, and OS participates in the development of idiopathic male infertility.


Subject(s)
Humans , Male , Fluorides/adverse effects , Semen , Polymorphism, Genetic , Glutathione Transferase/genetics , Glutathione S-Transferase pi/genetics , Infertility, Male/genetics , Genotype , Biomarkers , Genetic Predisposition to Disease , Case-Control Studies
3.
Asian Journal of Andrology ; (6): 58-65, 2023.
Article in English | WPRIM | ID: wpr-971003

ABSTRACT

Congenital bilateral absence of the vas deferens (CBAVD) is observed in 1%-2% of males presenting with infertility and is clearly associated with cystic fibrosis transmembrane conductance regulator (CFTR) mutations. CFTR is one of the most well-known genes related to male fertility. The frequency of CFTR mutations or impaired CFTR expression is increased in men with nonobstructive azoospermia (NOA). CFTR mutations are highly polymorphic and have established ethnic specificity. Compared with F508Del in Caucasians, the p.G970D mutation is reported to be the most frequent CFTR mutation in Chinese patients with cystic fibrosis. However, whether p.G970D participates in male infertility remains unknown. Herein, a loss-of-function CFTR p.G970D missense mutation was identified in a patient with CBAVD and NOA. Subsequent retrospective analysis of 122 Chinese patients with CBAVD showed that the mutation is a common pathogenic mutation (4.1%, 5/122), excluding polymorphic sites. Furthermore, we generated model cell lines derived from mouse testes harboring the homozygous Cftr p.G965D mutation equivalent to the CFTR variant in patients. The Cftr p.G965D mutation may be lethal in spermatogonial stem cells and spermatogonia and affect the proliferation of spermatocytes and Sertoli cells. In spermatocyte GC-2(spd)ts (GC2) Cftr p.G965D cells, RNA splicing variants were detected and CFTR expression decreased, which may contribute to the phenotypes associated with impaired spermatogenesis. Thus, this study indicated that the CFTR p.G970D missense mutation might be a pathogenic mutation for CBAVD in Chinese males and associated with impaired spermatogenesis by affecting the proliferation of germ cells.


Subject(s)
Humans , Animals , Mice , Male , Mutation, Missense , Retrospective Studies , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Infertility, Male/genetics , Mutation , Vas Deferens/abnormalities , Spermatogenesis/genetics
4.
Asian Journal of Andrology ; (6): 5-12, 2023.
Article in English | WPRIM | ID: wpr-970984

ABSTRACT

Spermatogenesis is regulated by several Y chromosome-specific genes located in a specific region of the long arm of the Y chromosome, the azoospermia factor region (AZF). AZF microdeletions are the main structural chromosomal abnormalities that cause male infertility. Assisted reproductive technology (ART) has been used to overcome natural fertilization barriers, allowing infertile couples to have children. However, these techniques increase the risk of vertical transmission of genetic defects. Despite widespread awareness of AZF microdeletions, the occurrence of de novo deletions and overexpression, as well as the expansion of AZF microdeletion vertical transmission, remains unknown. This review summarizes the mechanism of AZF microdeletion and the function of the candidate genes in the AZF region and their corresponding clinical phenotypes. Moreover, vertical transmission cases of AZF microdeletions, the impact of vertical inheritance on male fertility, and the prospective direction of research in this field are also outlined.


Subject(s)
Humans , Male , Azoospermia/genetics , Sex Chromosome Aberrations , Prospective Studies , Chromosome Deletion , Chromosomes, Human, Y/genetics , Infertility, Male/genetics , Sertoli Cell-Only Syndrome/genetics , Oligospermia/genetics
5.
Chinese Journal of Medical Genetics ; (6): 26-30, 2023.
Article in Chinese | WPRIM | ID: wpr-970872

ABSTRACT

OBJECTIVE@#To explore the incidence of azoospermia factor c (AZFc) microdeletion among patients with azoospermia or severe oligospermia, its association with sex hormone/chromosomal karyotype, and its effect on the outcome of pregnancy following intracytoplasmic sperm injection (ICSI) treatment.@*METHODS@#A total of 1 364 males with azoospermia or severe oligospermia who presented at the Affiliated Maternity and Child Health Care Hospital of Jiaxing College between 2013 and 2020 were subjected to AZF microdeletion and chromosome karyotyping analysis. The level of reproductive hormones in patients with AZFc deletions was compared with those of control groups A (with normal sperm indices) and B (azoospermia or severe oligospermia without AZFc microdeletion). The outcome of pregnancies for the AZFc-ICSI couples was compared with that of the control groups in regard to fertilization rate, superior embryo rate and clinical pregnancy rate.@*RESULTS@#A total of 51 patients were found to harbor AZFc microdeletion, which yielded a detection rate of 3.74%. Seven patients also had chromosomal aberrations. Compared with control group A, patients with AZFc deletion had higher levels of PRL, FSH and LH (P < 0.05), whilst compared with control group B, only the PRL and FSH were increased (P < 0.05). Twenty two AZFc couples underwent ICSI treatment, and no significant difference was found in the rate of superior embryos and clinical pregnancy between the AZFc-ICSI couples and the control group (P > 0.05).@*CONCLUSION@#The incidence of AZFc microdeletion was 3.74% among patients with azoospermia or severe oligospermia. AZFc microdeletion was associated with chromosomal aberrations and increased levels of PRL, FSH and LH, but did not affect the clinical pregnancy rate after ICSI treatment.


Subject(s)
Child , Humans , Male , Female , Pregnancy , Azoospermia/genetics , Oligospermia/genetics , Incidence , Chromosome Deletion , Chromosomes, Human, Y/genetics , Semen , Infertility, Male/genetics , Chromosome Aberrations , Follicle Stimulating Hormone/genetics
6.
Asian Journal of Andrology ; (6): 243-247, 2022.
Article in English | WPRIM | ID: wpr-928553

ABSTRACT

Thanks to tremendous advances in sequencing technologies and in particular to whole exome sequencing (WES), many genes have now been linked to severe sperm defects. A precise genetic diagnosis is obtained for a minority of patients and only for the most severe defects like azoospermia or macrozoospermia which is very often due to defects in the aurora kinase C (AURKC gene. Here, we studied a subject with a severe oligozoospermia and a phenotypic diagnosis of macrozoospermia. AURKC analysis did not reveal any deleterious variant. WES was then initiated which permitted to identify a homozygous loss of function variant in the zinc finger MYND-type containing 15 (ZMYND15 gene. ZMYND15 has been described to serve as a switch for haploid gene expression, and mice devoid of ZMYND15 were shown to be sterile due to nonobstructive azoospermia (NOA). In man, ZMYND15 has been associated with NOA and severe oligozoospermia. We confirm here that the presence of a bi-allelic ZMYND15 variant induces a severe oligozoospermia. In addition, we show that severe oligozoospermia can be associated macrozoospermia, and that a phenotypic misdiagnosis is possible, potentially delaying the genetic diagnosis. In conclusion, genetic defects in ZMYND15 can induce complete NOA or severe oligozoospermia associated with a very severe teratozoospermia. In our experience, severe oligozoospermia is often associated with severe teratozoospermia and can sometimes be misinterpreted as macrozoospermia or globozoospermia. In these instances, specific AURKC or dpy-19 like 2 (DPY19L2) diagnosis is usually negative and we recommend the direct use of a pan-genomic techniques such as WES.


Subject(s)
Animals , Humans , Male , Mice , Azoospermia/genetics , Infertility, Male/genetics , Membrane Proteins/genetics , Mutation , Oligospermia/genetics , Repressor Proteins/metabolism , Teratozoospermia/genetics
7.
Asian Journal of Andrology ; (6): 248-254, 2022.
Article in English | WPRIM | ID: wpr-928551

ABSTRACT

Apparently balanced chromosomal structural rearrangements are known to cause male infertility and account for approximately 1% of azoospermia or severe oligospermia. However, the underlying mechanisms of pathogenesis and etiologies are still largely unknown. Herein, we investigated apparently balanced interchromosomal structural rearrangements in six cases with azoospermia/severe oligospermia to comprehensively identify and delineate cryptic structural rearrangements and the related copy number variants. In addition, high read-depth genome sequencing (GS) (30-fold) was performed to investigate point mutations causative of male infertility. Mate-pair GS (4-fold) revealed additional structural rearrangements and/or copy number changes in 5 of 6 cases and detected a total of 48 rearrangements. Overall, the breakpoints caused truncations of 30 RefSeq genes, five of which were associated with spermatogenesis. Furthermore, the breakpoints disrupted 43 topological-associated domains. Direct disruptions or potential dysregulations of genes, which play potential roles in male germ cell development, apoptosis, and spermatogenesis, were found in all cases (n = 6). In addition, high read-depth GS detected dual molecular findings in case MI6, involving a complex rearrangement and two point mutations in the gene DNAH1. Overall, our study provided the molecular characteristics of apparently balanced interchromosomal structural rearrangements in patients with male infertility. We demonstrated the complexity of chromosomal structural rearrangements, potential gene disruptions/dysregulation and single-gene mutations could be the contributing mechanisms underlie male infertility.


Subject(s)
Humans , Male , Azoospermia/genetics , Chromosome Aberrations , Infertility, Male/genetics , Oligospermia/genetics , Translocation, Genetic
8.
Asian Journal of Andrology ; (6): 186-190, 2022.
Article in English | WPRIM | ID: wpr-928536

ABSTRACT

Nonobstructive azoospermia (NOA) is a common cause of infertility and is defined as the complete absence of sperm in ejaculation due to defective spermatogenesis. The aim of this study was to identify the genetic etiology of NOA in an infertile male from a Chinese consanguineous family. A homozygous missense variant of the membrane-bound O-acyltransferase domain-containing 1 (MBOAT1) gene (c.770C>T, p.Thr257Met) was found by whole-exome sequencing (WES). Bioinformatic analysis also showed that this variant was a pathogenic variant and that the amino acid residue in MBOAT1 was highly conserved in mammals. Quantitative polymerase chain reaction (Q-PCR) analysis showed that the mRNA level of MBOAT1 in the patient was 22.0% lower than that in his father. Furthermore, we screened variants of MBOAT1 in a broader population and found an additional homozygous variant of the MBOAT1 gene in 123 infertile men. Our data identified homozygous variants of the MBOAT1 gene associated with male infertility. This study will provide new insights for researchers to understand the molecular mechanisms of male infertility and will help clinicians make accurate diagnoses.


Subject(s)
Animals , Humans , Male , Acetyltransferases/genetics , Azoospermia/genetics , Cell Cycle Proteins/genetics , Infertility, Male/genetics , Mammals , Membrane Proteins/genetics , Mutation
9.
Asian Journal of Andrology ; (6): 67-72, 2022.
Article in English | WPRIM | ID: wpr-928515

ABSTRACT

Acephalic spermatozoa syndrome is a rare type of teratozoospermia that severely impairs the reproductive ability of male patients, and genetic defects have been recognized as the main cause of acephalic spermatozoa syndrome. Spermatogenesis and centriole-associated 1 like (SPATC1L) is indispensable for maintaining the integrity of sperm head-to-tail connections in mice, but its roles in human sperm and early embryonic development remain largely unknown. Herein, we conducted whole-exome sequencing (WES) of 22 infertile men with acephalic spermatozoa syndrome. An in silico analysis of the candidate variants was conducted, and WES data analysis was performed using another cohort consisting of 34 patients with acephalic spermatozoa syndrome and 25 control subjects with proven fertility. We identified biallelic mutations in SPATC1L (c.910C>T:p.Arg304Cys and c.994G>T:p.Glu332X) from a patient whose sperm displayed complete acephalia. Both SPATC1L variants are rare and deleterious. SPATC1L is mainly expressed at the head-tail junction of elongating spermatids. Plasmids containing pathogenic variants decreased the level of SPATC1L in vitro. Moreover, none of the patient's four attempts at intracytoplasmic sperm injection (ICSI) resulted in a transplantable embryo, which suggests that SPATC1L defects might affect early embryonic development. In conclusion, this study provides the first identification of SPATC1L as a novel gene for human acephalic spermatozoa syndrome. Furthermore, WES might be applied for patients with acephalic spermatozoa syndrome who exhibit reiterative ICSI failures.


Subject(s)
Humans , Male , Centrioles/genetics , Homozygote , Infertility, Male/genetics , Mutation , Spermatogenesis/genetics , Spermatozoa
10.
Asian Journal of Andrology ; (6): 40-44, 2022.
Article in English | WPRIM | ID: wpr-928507

ABSTRACT

Semen analysis has long been used to evaluate male fertility. Recently, several sperm function tests have been developed. Of those, the sperm DNA fragmentation index (DFI), which describes the status of the sperm DNA, is thought to be a suitable parameter for evaluating male fertility. However, there have been no large-scale studies on the sperm DFI of Japanese men. Therefore, we investigated the feasibility of using an in-house flow cytometry-based sperm DFI analysis based on the sperm DNA fragmentation test of sperm chromatin structure assay (SCSA) to assess male fertility in Japan. This study enrolled 743 infertile and 20 fertile Japanese men. To evaluate reproducibility, inter- and intraobserver precision was analyzed. A receiver operating characteristic curve analysis was used to set a cutoff value for the sperm DFI to identify men who could father children by timed intercourse or intrauterine insemination. The variability of the sperm DFI among fertile volunteers was determined. The relationship between semen parameters and the sperm DFI was assessed by Spearman's rho test. A precision analysis revealed good reproducibility of the sperm DFI. The cutoff value of sperm DNA fragmentation in infertile men was 24.0%. Semen volume had no relationship with the sperm DFI. Sperm concentration, sperm motility, total motile sperm count, and percentage of normal-shaped sperm were significantly and negatively correlated with the sperm DFI. The median sperm DFI was smaller in fertile volunteers (7.7%) than that in infertile men (19.4%). Sperm DNA fragmentation analysis can be used to assess sperm functions that cannot be evaluated by ordinary semen analysis.


Subject(s)
Child , Humans , Male , Chromatin , DNA Fragmentation , Flow Cytometry , Infertility, Male/genetics , Japan , Reproducibility of Results , Sperm Motility , Spermatozoa
11.
Int. braz. j. urol ; 47(2): 275-283, Mar.-Apr. 2021. tab, graf
Article in English | LILACS | ID: biblio-1154474

ABSTRACT

ABSTRACT Purpose: Sperm DNA fragmentation is a major cellular mechanism underlying varicocele-related male infertility. However, the type of DNA fragmentation - whether oxidative or of another nature - remains unknown. Thus, the aim of this study was to evaluate single- and double-stranded sperm DNA fragmentation, and oxidative-induced sperm DNA damage in men with varicocele. Materials and Methods: A cross-sectional study was performed, including 94 normozoospermic adults, of which 39 men without varicocele (controls) and 55 men with varicocele grades II or III, uni- or bilaterally. All men collected semen by masturbation. After semen analysis, the remaining volume was used for evaluation of three types of sperm DNA damage: (i) total DNA fragmentation, using an alkaline comet assay, (ii) double-stranded DNA fragmentation, using a neutral comet assay, and (iii) oxidative DNA damage, using an alkaline comet assay associated with the DNA glycosylase formamidopyrimidine enzyme. In each assay, percentage of sperm with any degree of DNA fragmentation, and with high DNA fragmentation were compared between the groups using an unpaired Student's t test or a Mann-Whitney test. Results: The varicocele group presented a higher rate of sperm with fragmented DNA (both any and high DNA fragmentation), considering single-stranded DNA fragmentation, double-stranded DNA fragmentation, or a combination of both, as well as oxidative- induced DNA fragmentation. Conclusions: Patients with varicocele have an increase in sperm DNA fragmentation levels, particularly in oxidative stress-induced sperm DNA damage.


Subject(s)
Humans , Male , Adult , Varicocele/genetics , Infertility, Male/genetics , Sperm Motility , Spermatozoa , Cross-Sectional Studies , Oxidative Stress , DNA Fragmentation
12.
Chinese Journal of Medical Genetics ; (6): 849-852, 2021.
Article in Chinese | WPRIM | ID: wpr-921953

ABSTRACT

OBJECTIVE@#To explore the clinical feature and gene variant for two cases of primary male infertility caused by severe asthenospermia and to analyze the etiology of the disease.@*METHODS@#Genomic DNA of peripheral blood samples of patients and their parents was extracted and gene variant analysis of the patients was conducted by using whole exome sequencing. Suspected pathogenic variant was verified by Sanger sequencing and pathogenic analysis.@*RESULTS@#Whole exome sequencing showed that the DNAH1 gene of patient 1 had two heterozygous variants of c.2016T>G(p.Y672X) and c.6017T>G (p.V2006G). The DNAH1 gene of patient 2 had a homozygous variant of c.2610G>A(p.W870X), which were inherited from his father and mother, respectively. According to American College of Medical Genetics and Genomics standards and guidelines, the c.2016T>G (p.Y672X) and c.2610G>A (p.W870X) varaints of DNAH1 gene were predicted to be pathogenic (PVS1+PM2+PM3+PP3).@*CONCLUSION@#The two patients of multiple morphological abnormalities of the sperm flagella may be caused by DNAH1 gene variant, which has resulted in primary male infertility.


Subject(s)
Humans , Male , Dyneins/genetics , Genomics , Infertility, Male/genetics , Mutation , Sperm Tail/pathology , Exome Sequencing
13.
Chinese Journal of Medical Genetics ; (6): 188-193, 2021.
Article in Chinese | WPRIM | ID: wpr-879553

ABSTRACT

DNA methylation as an important aspect of epigenetics plays an important role in spermatogenesis and embryonic development. In recent years, researchers have found that male infertility, in particular abnormal semen quality, is related to abnormal DNA methylation. To further delineate the pathogenesis of male infertility and inspire new ideas for the treatment of male infertility, a comprehensive review over the correlation between abnormal methylation of imprinted genes, repetitive DNA elements and non-imprinted genes, semen quality (including sperm count, morphology, and vitality) and male infertility is provided.


Subject(s)
Humans , Male , DNA Methylation , Infertility, Male/genetics , Semen Analysis , Sperm Count , Spermatogenesis , Spermatozoa/pathology
14.
Journal of Peking University(Health Sciences) ; (6): 803-807, 2021.
Article in Chinese | WPRIM | ID: wpr-942257

ABSTRACT

To explore the genetic causes of 3 male infertility patients with acephalospermia and the outcome of assisted reproductive technology. Clinical diagnosis, sperm morphology examination, sperm transmission electron microscopy examination were performed on 3 patients, and the whole exome sequencing technology was used for screening, Sanger sequencing verification, mutation pathogenicity analysis, and protein sequence homology comparison. Assisted reproductive technology was implemented to assist pregnancy treatment. The 3 patients were all sporadic infertile men, aged 25, 42 and 26 years, and there was no obvious abnormality in the general physical examination. Male external genitalia developed normally, bilateral testicles were normal in volume, and bilateral epididymis and spermatic vein were palpated without nodules, cysts, and tenderness. Repeated semen analysis showed that a large number of immature sperm could be seen, and they had the ability to move. The SUN5 gene of the 3 male infertile patients was a case of homozygous missense mutation c.7C>T (p.Arg3Trp), a case of compound heterozygous missense mutation c.1067G>A (p.Arg356His) and nonsense mutation c.216G>A (p.Trp72*) and a case of homozygous missense mutation c.1043A>T (p.Asn348Ile), of which c.7C>T (p.Arg3Trp) and c.1067G>A (p.Arg356His) were new variants that had not been reported. SIFT, Mutation Taster and PolyPhen-2 software function prediction results were all harmful, the nonsense mutation c.216G>A (p.Trp72*) led to the premature termination of peptide chain synthesis which might have a greater impact on protein function. The homology regions in the protein sequence homology alignment were all highly conserved.The 3 male patients and their spouses obtained 4 biological offspring through intracytoplasmic sperm injection, all of which were boys, and one of them was a twin.Three male infertile patients might be caused by SUN5 gene mutations. Such patients could obtain their biological offspring through assisted reproductive technology. It was still necessary to pay attention to the genetic risk of ASS, it was recommended that both men and women conduct genetic counseling and screening at the same time. In clinical diagnosis, whole exome sequencing technology could be used to perform auxiliary examinations to determine the treatment plan and assisted reproductive methods as soon as possible to reduce the burden on the family and society. The newly discovered mutation sites of SUN5 gene provided clues and directions for elucidating the pathogenic mechanism, and at the same time expanded the pathogenic mutation spectrum of ASS.


Subject(s)
Female , Humans , Male , Pregnancy , Infertility, Male/genetics , Membrane Proteins/genetics , Mutation , Sperm Injections, Intracytoplasmic , Spermatozoa
15.
Braz. j. med. biol. res ; 53(3): e8980, 2020. tab
Article in English | LILACS | ID: biblio-1089344

ABSTRACT

The mosaic 45,X/46,XY karyotype is a common sex chromosomal abnormality in infertile men. Males with this mosaic karyotype can benefit from assisted reproductive therapies, but the transmitted abnormalities contain 45,X aneuploidy as well as Y chromosome microdeletions. The aim of this study was to investigate the clinical and genetic characteristics of infertile men diagnosed with 45,X/46,XY mosaicism in China. Of the 734 infertile men found to carry chromosomal abnormalities, 14 patients were carriers of 45,X/46,XY mosaicism or its variants, giving a prevalence of 0.27% (14/5269) and accounting for 1.91% (14/734) of patients with a chromosomal abnormality. There were ten cases (71.43%, 10/14) of 45,X mosaicism exhibiting AZF microdeletions. Case 1 and Case 4 had AZFc deletions, and the other eight cases had AZFb+c deletions. A high frequency of Y chromosome microdeletions were detected in male patients with 45,X/46,XY mosaicism. Preimplantation genetic diagnosis should be offered to men having intracytoplasmic sperm injection for hypospermatogenesis caused by 45,X/46,XY mosaicism, to avoid the risk of transfering AZF microdeletions in addition to X monosomy in male offspring.


Subject(s)
Humans , Male , Adult , Middle Aged , Sex Chromosome Disorders of Sex Development/genetics , Infertility, Male/genetics , Mosaicism , Sex Chromosome Aberrations , China , Polymerase Chain Reaction , Chromosome Deletion , Chromosomes, Human, Y/genetics , Karyotyping
16.
Int. braz. j. urol ; 44(4): 785-793, July-Aug. 2018. tab
Article in English | LILACS | ID: biblio-954068

ABSTRACT

ABSTRACT Objective: To explore the clinical features of carriers of chromosome 2 translocations, enabling informed genetic counseling of these patients. Materials and Methods: Eighty-two male carriers of a translocation who were infertile or receiving fertility counseling were recruited. Cytogenetic analyses were performed using G-banding. A search of PubMed was performed to determine whether the identified translocations on chromosome 2 are involved in male infertility. The relationships of translocation breakpoints with male infertility and recurrent pregnancy loss were analyzed. Results: Of the 82 translocation carriers, 9 (11%) were carriers of a chromosome 2 translocation. Four cases had oligozoospermia or infertility, while five had normal semen. In an analysis of the literature, 55 patients who were carriers of chromosome 2 translocations were also reviewed. Breakpoints at 2p13 and 2q31 were observed in six patients each, and were the most common. Breakpoints at 2p23, 2p13, 2p11.2, 2q31, and 2q37 were associated to both pre-gestational and gestational infertility, while other breakpoints were associated with gestational infertility. Conclusions: All breakpoints at chromosome 2 were correlated with gestational infertility. Carriers of chromosome 2 translocations should therefore receive counseling to continue with natural conception and use of different technologies available via assisted reproductive technology, such as preimplantation genetic diagnosis.


Subject(s)
Humans , Male , Female , Pregnancy , Translocation, Genetic/genetics , Chromosomes, Human, Pair 2/genetics , Infertility, Male/genetics , Reference Standards , Pregnancy Outcome , Cytogenetic Analysis , Semen Analysis , Chromosome Breakpoints , Genetic Counseling , Genetic Carrier Screening
17.
Asian Journal of Andrology ; (6): 260-264, 2018.
Article in English | WPRIM | ID: wpr-1009566

ABSTRACT

In about half the cases of involuntary childlessness, a male infertility factor is involved. The PIWI-LIKE genes, a subclade of the Argonaute protein family, are involved in RNA silencing and transposon control in the germline. Knockout of murine Piwi-like 1 and 2 homologs results in complete infertility in males. The aim of this study was to analyze whether the mRNA expression of human PIWI-LIKE 1-4 genes is altered in ejaculated spermatozoa of men with impaired sperm characteristics. Ninety male participants were included in the study, among which 47 were with normozoospermia, 36 with impaired semen characteristics according to the World Health Organization (WHO) manual, 5th edition, and 7 with azoospermia serving as negative control for the PIWI-LIKE 1-4 mRNA expression in somatic cells in the ejaculate. PIWI-LIKE 1-4 mRNA expression in the ejaculated spermatozoa of the participants was measured by quantitative real-time PCR. In nonazoospermic men, PIWI-LIKE 1-4 mRNA was measurable in ejaculated spermatozoa in different proportions. PIWI-LIKE 1 (100.0%) and PIWI-LIKE 2 (49.4%) were more frequently expressed than PIWI-LIKE 3 (9.6%) and PIWI-LIKE 4 (15.7%). Furthermore, a decreased PIWI-LIKE 2 mRNA expression showed a significant correlation with a decreased sperm count (P = 0.022) and an increased PIWI-LIKE 1 mRNA expression with a decreased progressive motility (P = 0.048). PIWI-LIKE 1 and PIWI-LIKE 2 mRNA expression exhibited a significant association with impaired sperm characteristics and may be a useful candidate for the evaluation of the impact of PIWI-LIKE 1-4 mRNA expression on male infertility.


Subject(s)
Adult , Humans , Male , Middle Aged , Young Adult , Argonaute Proteins/genetics , Azoospermia/genetics , Case-Control Studies , Gene Expression , Infertility, Male/genetics , RNA, Messenger/metabolism , RNA-Binding Proteins , Sperm Count , Sperm Motility/genetics , Spermatozoa/metabolism
18.
Journal of Peking University(Health Sciences) ; (6): 774-777, 2018.
Article in Chinese | WPRIM | ID: wpr-941700

ABSTRACT

OBJECTIVE@#To explore the incidience of chromosome abnormality of the patients with oligozoospermia or azoospermia and male infertility, to discuss the relationship between the quantitative and structural abnormality of chromosome and to lay the foundation for the clinical diagnosis and consultation.@*METHODS@#A retrospective analysis was conducted from January 1, 2015 to May 1, 2016, in the Center for Reproduction Medicine, the Second Hospital of Jilin University, with male reproductive abnormalities history excluded. In the study, 1 324 cases were included with 448 cases of azoospermia and 876 cases of oligozoospermia. All the patients through ultrasound examination, color Doppler ultrasonography, the seminal plasma Zn determination, their hormone level determination, chromosome karyotype (the perinatal blood samples were obtained from the 1 324 patients with oligozoospermia or azoospermia for lymphocyte culture, then chromosomal specimens were prepared, G-banding analyses combined with clinical data were used to statistically analyze the incidence of chromosomal abnormality), Y chromosome azoospermia factor [PCR technique was used to detect SY157 locus, SY254 locus, and SY255 locus in male Y chromosome azoospermia factor (AZF) gene of the patients with oligozoospermia or azoospermia]. The relationship between chromosome abnormalities and oligozoospermia or azoospermia were analyzed.@*RESULTS@#Among the 876 cases of oligospermia patients, 78 cases were chromosome number abnormality and chromosomal structural abnormality, the abnormal number of sex chromosomes in 22 cases, and sex chromosomes and chromosome structural abnormalities in 56 cases; in the 448 cases of azoospermia patients, 91 cases were chromosomal structural abnormality and chromosome number abnormality, of them, 78 cases were of abnormal number of sex chromosomes, and 13 cases were of abnormal structure. In addition, 137 cases were of chromosome polymorphism in all the 1 324 patients, The incidence of Y chromosome abnormality in azoospermatism was higher than that of the 43 patients with Y chromosome AZF microdeletion. In addition, the asthenospermia and recurrent spontaneous abortion were closely related to Y chromosome abnormality and the chromosome translocations and inversions.@*CONCLUSION@#Oligozoospermia and azoospermia patients with abnormal chromosome karyotype have high incidence rate, and chromosome karyotype analyses were carried out on it, which is conducive to clinical diagnosis for the patients with abnormal chromosome karyotype. There is a close relationship between male infertility and abnormal karyotype. It is conducive to clinical diagnosis for the patients with infertility through chromosome karyotye analysis, which also provides evidence for genetic counseling.


Subject(s)
Humans , Male , Azoospermia/genetics , Chromosome Aberrations , Chromosome Deletion , Chromosomes, Human, Y , Infertility, Male/genetics , Oligospermia/genetics , Retrospective Studies
19.
Journal of Peking University(Health Sciences) ; (6): 729-731, 2018.
Article in Chinese | WPRIM | ID: wpr-941692

ABSTRACT

One case of family chromosomal karyotype with complex chromosomal translocation and male infertility was reported. This case is a male, 30 years old, Han nationality, who did not receive contraception for 3 years after marriage. The phenotype and intelligence of the patients were normal, and there were no abnormalities in the external genitalia. No abnormalities were found in the prostate and spermatic vein. There was no history of parotitis or testicular trauma, no history of smoking, drinking history, denial of harmful substances and history of radioactive contact. There were no similar patients in the family, and the secondary sex was normal. The routine semen examination suggested that the active sperm was seldom seen. There were no obvious abnormalities in the serum endocrine examination of the patient. Cytogenetic examination: the patient's karyotype 46XY, t (10; 18; 21) (q22; p11.2; q11.2). There was no deletion in locus sY84, sY86, sY127, sY134, sY143, sY254 and sY255. His wife's examination showed no obvious abnormality, and her karyotype was normal. The parents of the patients were not close relatives. Their father's chromosome karyotype analysis was 46, XY, and Y chromosome microdeletion was normal. The chromosome karyotype of the parent was 46XX, t (10; 18; 21), and the parents of the patient also had a daughter, whose phenotype and intellectual development were normal, chromosome karyotype 46XX, t (10; 18; 21). In this case, the patient's balance translocation should be inherited by the mother. Because of the normal phenotype of the patient, there was no loss of genetic material, but the abnormal chromosomes might be passed to the offspring, and the proportion of the unbalanced gametes was very high. Through systematic review and review of the cases, it was concluded that the balanced translocation carriers only changed the relative position of the translocation segments on the chromosomes, retained the total number of the original genes, only changed the relative position of the genes on the chromosomes, and had no serious effect on the role of the gene and the development of the individual. The phenotype was normal. The patients were given symptomatic treatment to improve semen quality. It is recommended that pre-implantation genetic screening/diagnosis(PGS/PGD) be performed if necessary. It is to guide married men and women to choose the appropriate childbearing age, avoid unhealthy environmental contacts, and strengthen genetic screening before and after pregnancy, so as to achieve the goal of eugenics.


Subject(s)
Adult , Female , Humans , Male , Pregnancy , Chromosome Deletion , Chromosomes, Human, Y , Infertility, Male/genetics , Karyotype , Semen Analysis , Translocation, Genetic
20.
Int. braz. j. urol ; 43(4): 770-775, July-Aug. 2017. tab, graf
Article in English | LILACS | ID: biblio-892858

ABSTRACT

ABSTRACT Objective To present clinical, chromosomal and hormonal features of ten cases with SRY-positive 46,XX testicular disorder of sex development who were admitted to our infertility clinic. Cases and Methods Records of the cases who were admitted to our infertility clinic between 2004 and 2015 were investigated. Ten 46,XX testicular disorder of sex development cases were detected. Clinical, hormonal and chromosomal assessments were analized. Results Mean age at diagnosis was 30.4, mean body height was 166.9cm. Hormonal data indicated that the patients had a higher FSH, LH levels, lower TT level and normal E2, PRL levels. Karyotype analysis of all patients confirmed 46,XX karyotype, and FISH analysis showed that SRY gene was positive and translocated to Xp. The AZFa, AZFb and AZFc regions were absent in 8 cases. In one case AZFb and AZFc incomplete deletion and normal AZFa region was present. In the other one all AZF regions were present. Conclusion Gonadal development disorders such as SRY-positive 46,XX testicular disorder of sex development can be diagnosed in infertility clinics during infertility work-up. Although these cases had no chance of bearing a child, they should be protected from negative effects of testosterone deficiency by replacement therapies.


Subject(s)
Humans , Male , Adult , 46, XX Testicular Disorders of Sex Development/genetics , Infertility, Male/genetics , Retrospective Studies , 46, XX Testicular Disorders of Sex Development/blood , Karyotype , Infertility, Male/blood
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