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BMC Medical Genomics Sep 2023Considering the essential roles that genetic factors play in azoospermia and oligospermia, this study aims to identify abnormal chromosomes using karyotyping and CNVs...
BACKGROUND
Considering the essential roles that genetic factors play in azoospermia and oligospermia, this study aims to identify abnormal chromosomes using karyotyping and CNVs and elucidate the associated genes in patients.
METHODS
A total of 1157 azoospermia and oligospermia patients were recruited, of whom, 769 and 674 underwent next-generation sequencing (NGS) to identify CNVs and routine G-band karyotyping, respectively.
RESULTS
First, 286 patients were co-analyzed using CNV sequencing (CNV-seq) and karyotyping. Of the 725 and 432 patients with azoospermia and oligospermia, 33.8% and 48.9% had abnormal karyotypes and CNVs, respectively. In particular, 47,XXY accounted for 44.18% and 26.33% of abnormal karyotypes and CNVs, respectively, representing the most frequent genetic aberration in azoospermia and oligospermia patients. Nevertheless, big Y and small Y accounted for 7.46% and 16.67% of abnormal karyotypes, respectively. We also identified high-frequency CNVs-loci, such as Xp22.31 and 2p24.3, in azoospermia and oligospermia patients.
CONCLUSION
Sex chromosome and autosomal CNV loci, such as Xp22.31 and 2p24.3, as well as the associated genes, such as VCX and NACAP9, could be candidate spermatogenesis genes. The high-frequency abnormal karyotypes, CNV loci, and hot genes represent new targets for future research.
Topics: Male; Humans; Azoospermia; Oligospermia; DNA Copy Number Variations; Karyotyping; Abnormal Karyotype
PubMed: 37684669
DOI: 10.1186/s12920-023-01652-2 -
Reproductive Sciences (Thousand Oaks,... May 2023The rate of infertility has globally increased in recent years for a variety of reasons. One of the main causes of infertility in men is azoospermia that is defined by... (Review)
Review
The rate of infertility has globally increased in recent years for a variety of reasons. One of the main causes of infertility in men is azoospermia that is defined by the absence of sperm in the ejaculate and classified into two categories: obstructive azoospermia and non-obstructive azoospermia. In non-obstructive azoospermia, genital ducts are not obstructed, but the testicles do not produce sperm at all, due to various reasons. Non-obstructive azoospermia in most cases has no therapeutic options other than assisted reproductive techniques, which in most cases require sperm donors. Here we discuss cell-based therapy approaches to restore fertility in men with non-obstructive azoospermia including cell-based therapies of non-obstructive azoospermia using regenerative medicine and cell-based therapies of non-obstructive azoospermia by paracrine and anti-inflammatory pathway, technical and ethical challenges for using different cell sources and alternative options will be described, and then the more effectual approaches will be mentioned as future trends.
Topics: Humans; Male; Azoospermia; Sperm Retrieval; Semen; Testis; Reproductive Techniques, Assisted
PubMed: 36380137
DOI: 10.1007/s43032-022-01115-6 -
Frontiers in Endocrinology 2022Non-coding RNAs are classified as small non-coding RNAs, long non-coding RNAs and circular RNAs, which are involved in a variety of biological processes, including cell... (Review)
Review
Non-coding RNAs are classified as small non-coding RNAs, long non-coding RNAs and circular RNAs, which are involved in a variety of biological processes, including cell differentiation, proliferation, apoptosis and pathological conditions of various diseases. Many studies have shown that non-coding RNAs are related to spermatogenesis, maturation, apoptosis, function, etc. In addition, the expression of non-coding RNAs in testicular tissue and semen of patients with non-obstructive azoospermia was different. However, the role of non-coding RNAs in the pathogenesis of non-obstructive azoospermia has not been fully elucidated, and the role of non-coding RNAs in non-obstructive azoospermia is rarely reviewed. Here we summarize the research progress of non-coding RNAs in the pathogenesis of non-obstructive azoospermia.
Topics: Azoospermia; Gene Expression Regulation; Humans; Male; RNA, Circular; RNA, Long Noncoding; Spermatogenesis
PubMed: 36060931
DOI: 10.3389/fendo.2022.959487 -
Seminars in Cell & Developmental Biology May 2014
Topics: Animals; Azoospermia; Humans; Male; Rats; Spermatogenesis; Spermatozoa; Testis
PubMed: 24796522
DOI: 10.1016/j.semcdb.2014.04.031 -
Clinics (Sao Paulo, Brazil) 2013Approximately 1% of all men in the general population suffer from azoospermia, and azoospermic men constitute approximately 10 to 15% of all infertile men. Thus, this... (Review)
Review
Approximately 1% of all men in the general population suffer from azoospermia, and azoospermic men constitute approximately 10 to 15% of all infertile men. Thus, this group of patients represents a significant population in the field of male infertility. A thorough medical history, physical examination and hormonal profile are essential in the evaluation of azoospermic males. Imaging studies, a genetic workup and a testicular biopsy (with cryopreservation) may augment the workup and evaluation. Men with nonobstructive azoospermia should be offered genetic counseling before their spermatozoa are used for assisted reproductive techniques. This article provides a contemporary review of the evaluation of the azoospermic male.
Topics: Azoospermia; Biopsy; Humans; Male; Oligospermia; Reproductive Techniques, Assisted; Sperm Count
PubMed: 23503952
DOI: 10.6061/clinics/2013(sup01)04 -
Aging May 2023Non-obstructive azoospermia (NOA) is a common cause of male infertility, and no specific diagnostic indicators exist. In this study, we used human testis datasets...
Non-obstructive azoospermia (NOA) is a common cause of male infertility, and no specific diagnostic indicators exist. In this study, we used human testis datasets GSE45885, GSE45887, and GSE108886 from GEO database as training datasets, and screened 6 signature genes (all lowly expressed in the NOA group) using Boruta algorithm and Lasso regression: C12orf54, TSSK6, OR2H1, FER1L5, C9orf153, XKR3. The diagnostic efficacy of the above genes was examined by constructing models with LightGBM algorithm: the AUC (Area Under Curve) of both ROC and Precision-Recall curves for internal validation was 1.0 ( < 0.05). For the external validation dataset GSE145467 (human testis), the AUC of its ROC curve was 0.9 and that of its Precision-Recall curve was 0.833 ( < 0.05). Next, we confirmed the cellular localization of the above genes using human testis single-cell RNA sequencing dataset GSE149512, which were all located in spermatid. Besides, the downstream regulatory mechanisms of the above genes in spermatid were inferred by GSEA algorithm: C12orf54 may be involved in the repression of E2F-related and MYC-related pathways, TSSK6 and C9orf153 may be involved in the repression of MYC-related pathways, while FER1L5 may be involved in the repression of spermatogenesis pathway. Finally, we constructed a NOA model in mice using X-ray irradiation, and quantitative Real-time PCR results showed that C12orf54, TSSK6, OR2H1, FER1L5, and C9orf153 were all lowly expressed in NOA group. In summary, we have identified novel signature genes of NOA using machine learning methods and complete experimental validation, which will be helpful for its early diagnosis.
Topics: Humans; Male; Animals; Mice; Testis; Azoospermia; Spermatogenesis; Infertility, Male
PubMed: 37227814
DOI: 10.18632/aging.204749 -
Journal of Ultrasound Sep 2022To assess the utility of comprehensive sonographic examination including scrotal sonography, Testicular Doppler and Transrectal Ultrasound (TRUS) to evaluate the male...
PURPOSE
To assess the utility of comprehensive sonographic examination including scrotal sonography, Testicular Doppler and Transrectal Ultrasound (TRUS) to evaluate the male reproductive system and differentiate between obstructive (OG) and non-obstructive (NOG) causes of azoospermia.
METHODS
30 infertile men with azoospermia and 30 control subjects with normospermia underwent sonographic evaluation. FNAC/biopsy findings were used for assigning a final diagnosis of obstructive or non-obstructive azoospermia. Qualitative and quantitative imaging parameters were retrospectively compared between the groups using Chi-square/Fisher's exact test and unpaired t-test, respectively. P < 0.05 was considered significant.
RESULTS
Ectasia of rete testis/epididymal tubules, altered epididymal echogenicity, dilated terminal vas deferens were significantly more common in OG while inhomogeneous testicular echo-texture and reduced testicular vascularity were more common in NOG (P < 0.05). Testicular volume and epididymal head size were significantly higher in OG than in NOG and controls (18.2 ml/10 mm Vs 8.2 ml/7.2 mm and 13.4 ml/8.8 mm respectively; P < 0.05); while Resistive Index (RI) of intra-testicular vessels was higher in NOG as compared to OG and controls (0.65 vs 0.54 and 0.52 respectively; P < 0.05). On ROC curve analysis, cut-off values of testicular volume (AUC: 0.939; P < 0.001), epididymal head size (AUC: 0.772; P = 0.001) and testicular RI (AUC: 0.761; P = 0.001) to differentiate between the groups were 12.1 ml (sensitivity-94.4%; specificity-83.3%), 9 mm (sensitivity-66.7%; specificity-71%) and 0.62 (sensitivity-62%; specificity-100%) respectively.
CONCLUSION
Comprehensive sonographic evaluation can be used to differentiate obstructive from non-obstructive infertility and should be routinely incorporated in the diagnostic workup of infertile men with azoospermia.
Topics: Azoospermia; Epididymis; Humans; Infertility, Male; Male; Retrospective Studies; Testis; Ultrasonography
PubMed: 35038143
DOI: 10.1007/s40477-021-00646-z -
Microbiology Spectrum Feb 2023Men with nonobstructive azoospermia (NOA) face the dual problems of low sperm count and low sperm quality. Most men with NOA without a clear cause are classified as...
Men with nonobstructive azoospermia (NOA) face the dual problems of low sperm count and low sperm quality. Most men with NOA without a clear cause are classified as having idiopathic NOA (iNOA). Previous studies found that microbes exist in semen, and the semen microbes of NOA men are different from those of normal men. However, the relevant mechanism is not clear. In this study, we answered the three questions of "who is there," "what is it doing," and "who is doing it" by combining 16s rRNA, nontargeted metabolome detection and metabolite traceability analysis. We found that the composition and interaction of seminal plasma microbes in the iNOA group changed. Metabolite traceability analysis and metabolic pathway analysis revealed that microbial abnormalities in the NOA group were closely related to the decrease of microbial degradation of toluene and the increase of metabolism of fructose or mannose. In addition, the metabolic relationship between microbes and the host in male semen in iNOA revealed that such microbes can produce harmful metabolites that affect sperm quality, the microbes compete with sperm for essential nutrients, and their presence reduces sperm production of essential nutrients. Idiopathic nonobstructive azoospermia is one of the great challenges in assisted reproductive therapy. Although microdissection testicular sperm extraction technology is currently available, many men with iNOA still face the problem of poor sperm retrieval and poor sperm quality. The role of seminal plasma microbes in male disease has been continuously investigated since semen was demonstrated to harbor commensal microbes. To our knowledge, this is the first detailed description of the microbe-host relationship in iNOA semen. This study is an important complement to research on the treatment and etiology of iNOA and the rationale for our ongoing research.
Topics: Humans; Male; Semen; Azoospermia; RNA, Ribosomal, 16S; Spermatozoa
PubMed: 36633411
DOI: 10.1128/spectrum.04365-22 -
Clinics (Sao Paulo, Brazil) 2013Azoospermia is a descriptive term referring to ejaculates that lack spermatozoa without implying a specific underlying cause. The traditional definition of azoospermia... (Review)
Review
Azoospermia is a descriptive term referring to ejaculates that lack spermatozoa without implying a specific underlying cause. The traditional definition of azoospermia is ambiguous, which has ramifications on the diagnostic criteria. This issue is further compounded by the apparent overlap between the definitions of oligospermia and azoospermia. The reliable diagnosis of the absence of spermatozoa in a semen sample is an important criterion not only for diagnosing male infertility but also for ascertaining the success of a vasectomy and for determining the efficacy of hormonal contraception. There appears to be different levels of rigor in diagnosing azoospermia in different clinical situations, which highlights the conflict between scientific research and clinical practice in defining azoospermia.
Topics: Azoospermia; Centrifugation; Humans; Male; Oligospermia; Semen Analysis
PubMed: 23503953
DOI: 10.6061/clinics/2013(sup01)05 -
Genetics in Medicine : Official Journal... Dec 2020Azoospermia affects 1% of men and it can be the consequence of spermatogenic maturation arrest (MA). Although the etiology of MA is likely to be of genetic origin, only...
PURPOSE
Azoospermia affects 1% of men and it can be the consequence of spermatogenic maturation arrest (MA). Although the etiology of MA is likely to be of genetic origin, only 13 genes have been reported as recurrent potential causes of MA.
METHODS
Exome sequencing in 147 selected MA patients (discovery cohort and two validation cohorts).
RESULTS
We found strong evidence for five novel genes likely responsible for MA (ADAD2, TERB1, SHOC1, MSH4, and RAD21L1), for which mouse knockout (KO) models are concordant with the human phenotype. Four of them were validated in the two independent MA cohorts. In addition, nine patients carried pathogenic variants in seven previously reported genes-TEX14, DMRT1, TEX11, SYCE1, MEIOB, MEI1, and STAG3-allowing to upgrade the clinical significance of these genes for diagnostic purposes. Our meiotic studies provide novel insight into the functional consequences of the variants, supporting their pathogenic role.
CONCLUSION
Our findings contribute substantially to the development of a pre-testicular sperm extraction (TESE) prognostic gene panel. If properly validated, the genetic diagnosis of complete MA prior to surgical interventions is clinically relevant. Wider implications include the understanding of potential genetic links between nonobstructive azoospermia (NOA) and cancer predisposition, and between NOA and premature ovarian failure.
Topics: Azoospermia; Cell Cycle Proteins; DNA-Binding Proteins; Dissection; Exome; Humans; Male; Testis; Exome Sequencing
PubMed: 32741963
DOI: 10.1038/s41436-020-0907-1