Molecular mechanisms of cellular dysfunction in testes from men with non-obstructive azoospermia

Nature Reviews Urology, Journal Year: 2023, Volume and Issue: 21(2), P. 67 - 90

Published: Dec. 18, 2023

Language: Английский

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OCT4 protein and gene expression analysis in the differentiation of spermatogonia stem cells into neurons by immunohistochemistry, immunocytochemistry, and bioinformatics analysis

Stem Cell Reviews and Reports, Journal Year: 2023, Volume and Issue: 19(6), P. 1828 - 1844

Published: April 29, 2023

Language: Английский

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Anti-Müllerian hormone predicts positive sperm retrieval in men with idiopathic non-obstructive azoospermia—findings from a multi-centric cross-sectional study

Human Reproduction, Journal Year: 2023, Volume and Issue: 38(8), P. 1464 - 1472

Published: June 15, 2023

Abstract STUDY QUESTION Is it possible to identify a reliable marker of successful sperm retrieval (+SR) in men with idiopathic non-obstructive azoospermia (iNOA) undergoing microdissection testicular extraction (mTESE)? SUMMARY ANSWER A higher likelihood +SR during mTESE is observed iNOA and lower preoperative serum anti-Müllerian hormone (AMH) levels, good predictive accuracy achieved using an AMH threshold <4 ng/ml. WHAT IS KNOWN ALREADY has been previously linked prior ART. DESIGN, SIZE, DURATION multi-centre cross-sectional study was carried out cohort 117 at three tertiary-referral centres. PARTICIPANTS/MATERIALS, SETTING, METHODS Data from consecutive white-European presenting for primary couple’s infertility associated pure male factor centres were analysed. Descriptive statistics applied compare patients negative (−SR) versus mTESE. Multivariate logistic regression models fitted predict mTESE, after adjusting confounders. Diagnostic the factors assessed. Decision curve analyses used display clinical benefit. MAIN RESULTS AND THE ROLE OF CHANCE Overall, 60 (51.3%) had −SR 57 (48.7%) Patients levels baseline (P = 0.005) estradiol (E2) 0.01). At multivariate analysis, (odds ratio: 0.79; 95% CI: 0.64–0.93, P 0.03) confounders (e.g. age, mean volume, FSH, E2). ng/ml highest AUC 70.3% (95% 59.8–80.7). analysis displayed net benefit threshold. LIMITATIONS, REASONS FOR CAUTION There need external validation even larger cohorts, across different ethnicities. Systematic reviews meta-analysis provide high level evidence are lacking context SR rates iNOA. WIDER IMPLICATIONS FINDINGS Current findings suggest that slightly more than one two significantly percentage surgery. circulating ensured satisfactory sensitivity, specificity, positive values FUNDING/COMPETING INTEREST(S) This work supported by voluntary donations Urological Research Institute (URI). All authors declare no conflict interest. TRIAL REGISTRATION NUMBER N/A

Language: Английский

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Clinical management, differential diagnosis, follow-up and biomarkers of infertile men with nonobstructive azoospermia

Translational Andrology and Urology, Journal Year: 2024, Volume and Issue: 13(2), P. 359 - 362

Published: Feb. 1, 2024

Language: Английский

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Whole transcriptome analysis to identify non-coding RNA regulators and hub genes in sperm of non-obstructive azoospermia by microarray, single-cell RNA sequencing, weighted gene co-expression network analysis, and mRNA-miRNA-lncRNA interaction analysis

BMC Genomics, Journal Year: 2024, Volume and Issue: 25(1)

Published: June 11, 2024

Abstract Background The issue of male fertility is becoming increasingly common due to genetic differences inherited over generations. Gene expression and evaluation non-coding RNA (ncRNA), crucial for sperm development, are significant factors. This gene can affect motility and, consequently, fertility. Understanding the intricate protein interactions that play essential roles in differentiation development vital. knowledge could lead more effective treatments interventions infertility. Materials methods Our research aim identify new key genes ncRNA involved non-obstructive azoospermia (NOA), improving diagnosis offering accurate estimates successful extraction based on an individual’s genotype. Results We analyzed transcript three NOA patients who tested negative issues, employing comprehensive genome-wide analysis approximately 50,000 sequences using microarray technology. compared profiles between normal sperm. found differences: 150 were up-regulated, 78 down-regulated, along with 24 ncRNAs up-regulated 13 down-regulated conditions. By cross-referencing our results a single-cell genomics database, we identified overexpressed biological process terms differentially expressed genes, such as “protein localization endosomes” “xenobiotic transport.” Overrepresented molecular function included “voltage-gated calcium channel activity,” “growth hormone-releasing hormone receptor “sialic acid transmembrane transporter activity.” Analysis revealed nine hub associated sperm: RPL34, CYB5B, GOL6A6, LSM1, ARL4A, DHX57, STARD9, HSP90B1 , VPS36 . Conclusions These their interacting proteins may role pathophysiology germ cell abnormalities

Language: Английский

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Functions and mechanism of noncoding RNA in regulation and differentiation of male mammalian reproduction

Cell Biochemistry and Function, Journal Year: 2023, Volume and Issue: 41(7), P. 767 - 778

Published: Aug. 16, 2023

Abstract Noncoding RNAs (ncRNAs) are active regulators of a wide range biological and physiological processes, including the majority mammalian reproductive events. Knowledge activities ncRNAs in context reproduction will allow for more comprehensive comparative understanding male sterility fertility. In this review, we describe recent advances ncRNA‐mediated control emphasize importance several aspects reproduction, such as germ cell biogenesis organ activity. Furthermore, focus on gene expression regulatory feedback loops hormones ncRNA to better understand commitment function. Finally, study shows role failure provides suggestions further research.

Language: Английский

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Altered G-Protein Transduction Protein Gene Expression in the Testis of Infertile Patients with Nonobstructive Azoospermia

DNA and Cell Biology, Journal Year: 2023, Volume and Issue: 42(10), P. 617 - 637

Published: Aug. 23, 2023

Recent studies have shown that several members of the G-protein-coupled receptors (GPCR) superfamily play crucial roles in maintenance ion-water homeostasis sperm and Sertoli cells, development germ formation blood barrier, maturation sperm. The GPCR, guanyl-nucleotide exchange factor, membrane traffic protein, small GTPase genes were analyzed by microarray bioinformatics (3513 cell genes). In analyses three human cases with different nonobstructive azoospermia sperm, expression GOLGA8IP, OR2AT4, PHKA1, A2M, OR56A1, SEMA3G, LRRC17, APP, ARHGAP33, RABGEF1, NPY2R, GHRHR, LTB4R2, GRIK5, OR6K6, NAPG, OR6C65, VPS35, FPR3, ARL4A was upregulated, while MARS, SIRPG, OGFR, GPR150, LRRK1, NGEF downregulated. There an increase GBP3, TNF, TGFB3, CLTC cells NOA, whereas PAQR4, RRAGD, RAC2, SERPINB8, IRPB1, MRGPRF, RASA2, RGS2, RAP2A, RAB2B, ARL17, SERINC4, XIAP, DENND4C, ANKRA2, CSTA, STX18, SNAP23 A combined analysis Enrich Shiny Gene Ontology (GO), STRING, Cytoscape used to predict proteins' molecular interactions then recognize master pathways. Functional enrichment showed biological process (BP), regulation protein metabolic process, GTPase-mediated signal transduction significantly expressed up-/downregulated differentially (DEGs) function (MF) experiments DEGs up-/downregulated, it found GPCR activity, guanyl ribonucleotide binding, activity nucleoside-triphosphatase overexpressed. An GO findings BP MF be common DEGs. When these gene mutations been validated, they can create new antagonists or agonists are receptor-selective.

Language: Английский

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Differential expression of ion channel coding genes in the endometrium of women experiencing recurrent implantation failures

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 27, 2024

Our study probed the differences in ion channel gene expression endometrium of women with Recurrent Implantation Failure (RIF) compared to fertile women. We analyzed relative genes coding for T-type Ca2+, ENaC, CFTR, and KCNQ1 channels endometrial samples from 20 RIF-affected 10 control women, aged 22-35, via microarray analysis quantitative real-time PCR. Additionally, we examined DNA methylation regulatory region using ChIP The bioinformatics component our research included Gene Ontology analysis, protein-protein interaction networks, signaling pathway mapping identify key biological processes pathways implicated RIF. This led discovery significant alterations RIF women's endometrium, most notably an overexpression CFTR reduced SCNN1A, SCNN1B, SCNN1G, CACNA1H, KCNQ1. A higher level KCNQ1's was also observed patients. Gene-set enrichment highlighted a presence involved transport membrane potential regulation, particularly sodium calcium complexes, which are vital cation movement across cell membranes. Genes were enriched broader transmembrane transporter underscoring their extensive role cellular homeostasis signaling. These findings suggest involvement pathology implantation failure, offering new insights into mechanisms behind possible therapeutic targets.

Language: Английский

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Nomogram based on a circular RNA biomarker for predicting the likelihood of successful sperm retrieval via microdissection testicular sperm extraction in patients with idiopathic non-obstructive azoospermia

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 17, 2023

Background Many circular RNAs (circRNAs) are specifically expressed in the testes and seminal plasma of patients with non-obstructive azoospermia (NOA), highlighting them as potential predictors microdissection testicular sperm extraction (micro-TESE) outcomes. Although research has indicated that RNA monoglyceride lipase (circ_MGLL) is highly tissues NOA, association between circ_MGLL expression retrieval outcomes (SROs) idiopathic (iNOA) receiving micro-TESE remains unclear. Methods This single-center, retrospective cohort study enrolled 114 iNOA who underwent at Northwest Women’s Children’s Hospital from January 2017 to November 2021. A logistic regression model was used examine associations SRO tissues, results which were conjunction previous findings establish a nomogram. The predictive performance circ_MGLL-based nomogram evaluated via calibration curves, receiver operating characteristic decision curve analysis (DCA) using an internal validation method. Results generalized additive probability successful for decreased increased tissues. Across entire cohort, univariate revealed inversely associated NOA. trend did not change after stratification according age, body mass index, volume, follicle-stimulating hormone (FSH) level, luteinizing (LH) testosterone (T) or pathological type (or adjusting these confounders) (odds ratio <1, P < 0.001). then generated by integrating circ_MGLL, types, FSH, LH, T levels. achieved satisfactory discrimination, area under 0.857, curves demonstrated impressive agreement. DCA net clinical benefit greater than alone. Conclusion significantly iNOA. developed current can predict high accuracy.

Language: Английский

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Exploring the interaction between immune cells in the prostate cancer microenvironment combining weighted correlation gene network analysis and single-cell sequencing: An integrated bioinformatics analysis

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 30, 2024

Language: Английский

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