Isotretinoin for the treatment of nonobstructive azoospermia: a pilot study.
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ABSTRACT:
SUBMITTER: Amory JK
PROVIDER: S-EPMC8451502 | biostudies-literature | 2021 Sep-Oct
REPOSITORIES: biostudies-literature
Publications
Isotretinoin for the treatment of nonobstructive azoospermia: a pilot study.
Amory John K JK Muller Charles H CH Walsh Thomas J TJ
Asian journal of andrology 20210901 5
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Project description:Nonobstructive azoospermia (NOA) refers to the failure of spermatogenesis, which affects approximately 1% of the male population and contributes to 10% of male infertility. NOA has an underlying basis of endocrine imbalances since proper human spermatogenesis relies on complex regulation and cooperation of multiple hormones. A better understanding of subtle hormonal disturbances in NOA would help design and improve hormone therapies with reduced risk in human fertility clinics. The purpose of this review is to summarize the research on the endocrinological aspects of NOA, especially the hormones involved in hypothalamic-pituitary-testis axis (HPTA), including gonadotropin-releasing hormone, follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone, estradiol, sex hormone binding globulin, inhibin B, anti-Müllerian hormone, and leptin. For the NOA men associated with primary testicular failure, the quality of currently available evidence has not been sufficient enough to recommend any general hormone optimization therapy. Some other NOA patients, especially those with hypogonadotropic hypogonadism, could be treated with hormonal replacement. Although these approaches have succeeded in resuming the fertility in many NOA patients, the prudent strategies should be applied in individuals according to specific NOA etiology by balancing fertility benefits and potential risks. This review also discusses how NOA can be induced by immunization against hormones.
| S-EPMC9226686 | biostudies-literature
Project description:The genetic background of the non-obstructive azoospermia (NOA) remains poorly known. However, recent studies employing next generation sequencing techniques were able to uncover some NOA causative genes, among which was the TKTL1 gene. In this article we aim to understand the function of the TKTL1 gene in human spermatogenesis by inducing its overexpression in human testicular primary cells (hTPc), which we verified in male gonad tissue samples collected from NOA patients by uncovering the genes cluster regulated by TKTL1. Successful overexpression of the TKTL1 gene was achieved in hTP cells, the TKTL1 gene expression level was significantly higher in modified cells compared to both control groups (p<0.01). Using RNA-seq, we selected 20 genes which expression levels significantly differed in the modified hTP cells overexpressing TKTL1 gene in comparison to both controls. Male gonad tissue samples collected from NOA patients harbouring a mutation in the TKTL1 gene showed a significant downregulation (p<0.05) in HERC5, CSF3, HES1 and HSPA1B genes, compared to both controls, which was in accordance with the results obtained for hTPc cells, as the overexpression of the TKTL1 gene correlated with an increased expression level of the named genes compared to control groups.
2025-05-01 | GSE262557 | GEO
Project description:The clinical management of men with nonobstructive azoospermia (NOA) seeking fertility has been a challenge for andrologists, urologists, and reproductive medicine specialists alike. This review presents a personal perspective on the clinical management of NOA, including the lessons learned over 15 years dealing with this male infertility condition. A five-consecutive-step algorithm is proposed to manage such patients. First, a differential diagnosis of azoospermia is made to confirm/establish that NOA is due to spermatogenic failure. Second, genetic testing is carried out not only to detect the males in whom NOA is caused by microdeletions of the long arm of the Y chromosome, but also to counsel the affected patients about their chances of having success in sperm retrieval. Third, it is determined whether any intervention prior to a surgical retrieval attempt may be used to increase sperm production. Fourth, the most effective and efficient retrieval method is selected to search for testicular sperm. Lastly, state-of-art laboratory techniques are applied in the handling of retrieved gametes and cultivating the embryos resulting from sperm injections. A coordinated multidisciplinary effort is key to offer the best possible chance of achieving a biological offspring to males with NOA.
| S-EPMC4430952 | biostudies-other
Project description: Not available
| S-EPMC10521963 | biostudies-literature
Project description:ObjectivePrimary ovarian insufficiency (POI) and Non-obstructive azoospermia (NOA) both represent disease states of early, and often complete, failure of gametogenesis. Because oogenesis and spermatogenesis share the same conserved steps in meiosis I, it is possible that inherited defects in meiosis I could lead to shared causes of both POI and NOA. Currently, known genes that contribute to both POI and NOA are limited. In this review article, we provide a systematic review of genetic mutations in which both POI and NOA phenotypes exist.Evidence reviewA PubMed literature review was conducted from January 1, 2000 through October 2020. We included all studies that demonstrated human cases of POI or NOA due to a specific genetic mutation either within the same family or in separate families.ResultsWe identified 33 papers that encompassed 10 genes of interest with mutations implicated in both NOA and POI. The genes were all involved in processes of meiosis I.ConclusionMutations in genes involved in processes of meiosis I may cause both NOA and POI. Identifying these unique phenotypes among shared genotypes leads to biologic plausibility that the key error occurs early in gametogenesis with an etiology shared among both male and female offspring. From a clinical standpoint, this shared relationship may help us better understand and identify individuals at high risk for gonadal failure within families and suggests that clinicians obtain history for opposite sex family members when approaching a new diagnosis of POI or NOA.
| S-EPMC9518791 | biostudies-literature
Project description:The aim of the present work was to present the outcomes of the patients with Y-chromosome microdeletions treated by intracytoplasmic sperm injection (ICSI), either using fresh (TESE) or frozen-thawed (TESE-C) testicular sperm and ejaculated sperm (EJAC). The originality of this work resides in the comparisons between the different types of Y-microdeletions (AZFa, AZFb, and AZFc) and treatments, with detailed demographic, stimulation, embryological, clinical, and newborn (NB) outcomes. Of 125 patients with Y-microdeletions, 33 patients presented severe oligozoospermia (18 performed ICSI with ejaculated sperm) and 92 secretory azoospermia (65 went for TESE with 40 having successful sperm retrieval and performed ICSI). There were 51 TESE treatment cycles and 43 TESE-C treatment cycles, with a birth of 19 NB (2 in AZFa/TESE-C, 12 in AZFc/TESE, and 5 in AZFc/TESE-C). Of the 29 EJAC cycles, there was a birth of 8 NB (in AZFc). In TESE and EJAC cycles, there were no significant differences in embryological and clinical parameters. In TESE-C cycles, there was a significant lower oocyte maturity rate, embryo cleavage rate and mean number of embryos transferred in AZFb, and a higher mean number of oocytes and lower fertilization rate in AZFc. In conclusion, although patients with AZFc microdeletions presented a high testicular sperm recovery rate and acceptable clinical outcomes, cases with AZFa and AZFb microdeletions presented a poor prognosis. Due to the reported heredity of microdeletions, patients should be informed about the infertile consequences on NB and the possibility of using preimplantation genetic diagnosis for female sex selection.
| S-EPMC5427791 | biostudies-literature
Project description:BackgroundGenetic causes that lead to spermatogenetic failure in patients with nonobstructive azoospermia (NOA) have not been yet completely established.ObjectiveTo identify low-frequency NOA-associated single nucleotide variants (SNVs) using whole-genome sequencing (WGS).Materials and methodsMen with various types of NOA (n = 39), including samples that had been previously tested with whole-exome sequencing (WES; n = 6) and did not result in diagnostic conclusions. Variants were annotated using the Ensembl Variant Effect Predictor, utilizing frequencies from GnomAD and other databases to provide clinically relevant information (ClinVar), conservation scores (phyloP), and effect predictions (i.e., MutationTaster). Structural protein modeling was also performed.ResultsUsing WGS, we revealed potential NOA-associated SNVs, such as: TKTL1, IGSF1, ZFPM2, VCX3A (novel disease causing variants), ESX1, TEX13A, TEX14, DNAH1, FANCM, QRICH2, FSIP2, USP9Y, PMFBP1, MEI1, PIWIL1, WDR66, ZFX, KCND1, KIAA1210, DHRSX, ZMYM3, FAM47C, FANCB, FAM50B (genes previously known to be associated with infertility) and ALG13, BEND2, BRWD3, DDX53, TAF4, FAM47B, FAM9B, FAM9C, MAGEB6, MAP3K15, RBMXL3, SSX3 and FMR1NB genes, which may be involved in spermatogenesis.Discussion and conclusionIn this study, we identified novel potential candidate NOA-associated genes in 29 individuals out of 39 azoospermic males. Note that in 5 out of 6 patients subjected previously to WES analysis, which did not disclose potentially causative variants, the WGS analysis was successful with NOA-associated gene findings.
| S-EPMC9826517 | biostudies-literature
Project description:Non-obstructive azoospermia (NOA) is the most severe form of male infertility owing to the absence of sperm during ejaculation as a result of failed spermatogenesis. The molecular mechanisms of NOA have not been well studied. Here, we revealed the dysregulated differentially expressed genes in NOA and related signaling pathways or biological processes. Cluster features of biological processes include spermatogenesis, fertilization, cilium movement, penetration of zona pellucida, sperm chromatin condensation, and being significantly enriched metabolic pathways in proximal tubule bicarbonate reclamation, aldosterone synthesis and secretion, glycolysis and glycogenesis pathways in NOA using Gene Ontology analysis and pathway enrichment analysis. The NOA gene co-expression network was constructed by weighted gene co-expression network analysis to identify the hub genes (CHD5 and SPTBN2). In addition, we used another Gene Expression Omnibus dataset (GSE45887) to validate these hub genes. Furthermore, we used the Seurat package to classify testicular tissue cells from NOA patients and to characterize the differential expression of hub genes in different cell types from different adult males based on the scRNA-seq dataset (GSE106487). These results provide new insights into the pathogenesis of NOA. Of particular note, CHD5 and SPTBN2 may be potential biomarkers for the diagnosis and treatment of NOA.
| S-EPMC7993690 | biostudies-literature
Project description:Nonobstructive azoospermia (NOA) represents the most severe expression of male infertility, involving around 1% of the male population and 10% of infertile men. This condition is characterised by the inability of the testis to produce sperm cells, and it is considered to have an important genetic component. During the last two decades, different genetic anomalies, including microdeletions of the Y chromosome, karyotype defects, and missense mutations in genes involved in the reproductive function, have been described as the primary cause of NOA in many infertile men. However, these alterations only explain around 25% of azoospermic cases, with the remaining patients showing an idiopathic origin. Recent studies clearly suggest that the so-called idiopathic NOA has a complex aetiology with a polygenic inheritance, which may alter the spermatogenic process. Although we are far from a complete understanding of the molecular mechanisms underlying NOA, the use of the new technologies for genetic analysis has enabled a considerable increase in knowledge during the last years. In this review, we will provide a comprehensive and updated overview of the genetic basis of NOA, with a special focus on the possible application of the recent insights in clinical practice.
| S-EPMC7074441 | biostudies-literature
Project description:Many studies have shown that microRNAs (miRNAs) play vital roles during the spermatogenesis. However, little is known about the altered miRNA profiles of testicular tissues in nonobstructive azoospermia (NOA). Using microarray technology, the miRNA expression profiles of testicular biopsies from patients with NOA and of normal testicular tissues were determined. Bioinformatics analyses were conducted to predict the enriched biological processes and functions of identified miRNAs. The microarray data were validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), the results of which were then validated with a larger sample size. Correlations between the miRNA expression levels and clinical characteristics were analyzed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic ability of miRNAs for azoospermia. Hierarchical clustering showed that 129 miRNAs were significantly differentially expressed between the NOA and control groups. Bioinformatics analysis indicated that the differentially expressed miRNAs were involved in spermatogenesis, cell cycle, and mitotic prometaphase. In the subsequent qRT-PCR assays, the selected miRNA expression levels were consistent with the microarray results, and similar validated results were obtained with a larger sample size. Some clinical characteristics were significantly associated with the expression of certain miRNAs. In particular, we identified a combination of two miRNAs (miR-10b-3p and miR-34b-5p) that could serve as a predictive biomarker of azoospermia. This study provides altered miRNA profiles of testicular biopsies from NOA patients and examines the roles of miRNAs in spermatogenesis. These profiles may be useful for predicting and diagnosing the presence of testicular sperm in individuals with azoospermia.
| S-EPMC6958976 | biostudies-literature