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Results for “non-obstructive azoospermia”

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5 recordsLinked to original sources
PubMed2025

Identification of novel cytoskeleton protein involved in spermatogenic cells and sertoli cells of non-obstructive azoospermia based on microarray and bioinformatics analysis.

BACKGROUND: During mammalian spermatogenesis, the cytoskeleton system plays a significant role in morphological changes. Male infertility such as non-obstructive azoospermia (NOA) might be explained by studies of the cytoskeletal system during spermatogenesis. METHODS: The cytoskeleton, scaffold, and actin-binding genes were analyzed by microarray and bioinformatics (771 spermatogenic cellsgenes and 774 Sertoli cell genes). To validate these findings, we cross-referenced our results with data from a single-cell genomics database. RESULTS: In the microarray analyses of three human cases with different NOA spermatogenic cells, the expression of TBL3, MAGEA8, KRTAP3-2, KRT35, VCAN, MYO19, FBLN2, SH3RF1, ACTR3B, STRC, THBS4, and CTNND2 were upregulated, while expression of NTN1, ITGA1, GJB1, CAPZA1, SEPTIN8, and GOLGA6L6 were downregulated. There was an increase in KIRREL3, TTLL9, GJA1, ASB1, and RGPD5 expression in the Sertoli cells of three human cases with NOA, whereas expression of DES, EPB41L2, KCTD13, KLHL8, TRIOBP, ECM2, DVL3, ARMC10, KIF23, SNX4, KLHL12, PACSIN2, ANLN, WDR90, STMN1, CYTSA, and LTBP3 were downregulated. A combined analysis of Gene Ontology (GO) and STRING, were used to predict proteins' molecular interactions and then to recognize master pathways. Functional enrichment analysis showed that the biological process (BP) mitotic cytokinesis, cytoskeleton-dependent cytokinesis, and positive regulation of cell-substrate adhesion were significantly associated with differentially expressed genes (DEGs) in spermatogenic cells. Moleculare function (MF) of DEGs that were up/down regulated, it was found that tubulin bindings, gap junction channels, and tripeptide transmembrane transport were more significant in our analysis. An analysis of GO enrichment findings of Sertoli cells showed BP and MF to be common DEGs. Cell-cell junction assembly, cell-matrix adhesion, and regulation of SNARE complex assembly were significantly correlated with common DEGs for BP. In the study of MF, U3 snoRNA binding, and cadherin binding were significantly associated with common DEGs. CONCLUSION: Our analysis, leveraging single-cell data, substantiated our findings, demonstrating significant alterations in gene expression patterns.

Male↗
PubMed2026

Proteomic insights into azoospermia: protein differences in testicular tissue between non-obstructive and obstructive azoospermia patients.

Non-obstructive azoospermia (NOA) and obstructive azoospermia (OA) are the main classifications of severe male infertility, but the molecular mechanism of NOA remains poorly understood. This study aimed to identify potential biomarkers and pathological mechanisms by comparing the proteomic differences in testicular tissues of NOA and OA patients. Through proteomic analysis based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) of testicular samples from 5 NOA patients and 5 OA patients, we identified 5264 proteins, among which 717 differentially expressed proteins (DEPs) were found between the two groups (242 upregulated and 475 downregulated in NOA). Bioinformatics analysis indicated that these DEPs were significantly associated with reproductive development, gametogenesis, and cell structural stability. On the basis of this, six candidate proteins, including dysferlin (DYSF), myoferlin (MYOF), mitsugumin 53 (MG53), cluster of differentiation 63 (CD63), caveolin-3 (CAV3), and calpain-3 (CAPN3), were selected from the DEPs and verified in an expanded sample set (37 NOA cases and 28 OA cases) through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, confirming their dysregulation in NOA. These findings provide new proteomic insights into NOA, highlighting the disruption of membrane repair and structural pathways, and offer potential biomarkers for understanding its pathogenesis.

Humans↗
PubMed2026

[Study of a patient with azoospermia due to variant of MOV10L1 gene].

OBJECTIVE: To explore the clinical and genotypic characteristics of a patient with Sertoli cell-only syndrome (SCOS) due to variants of MOV10L1 gene. METHODS: A 27-year-old patient with Non-obstructive azoospermia (NOA) underwent routine semen analysis. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), estradiol (E2), prolactin (PRL), and testosterone (T) were determined by chemiluminescence assays. Peripheral blood samples were collected for G-banded karyotyping analysis. Multiplex PCR fluorescence detection was used to screen for AZF gene microdeletions. Whole exome sequencing (WES) and Sanger sequencing were performed simultaneously. Testicular biopsy tissues were subjected to Hematoxylin-Eosin (HE) staining to assess seminiferous tubule cell composition, and MOV10L1 protein expression was detected by immunohistochemical staining. Bioinformatics tools were employed to predict the pathogenicity of variants and their impact on protein structure and function. This study was approved by the Medical Ethics Committee of the Guangdong Institute of Reproductive Sciences [Ethics No.: 2023(01)]. RESULTS: The patient's two semen analyses had failed to detect any sperm. Hormone tests indicated elevated FSH (22.32 mIU/mL) and PRL (397.6 mIU/mL), while T (3.68 nmol/L) and E2 (38.32 pmol/L) were reduced. Chromosomal karyotyping revealed 46,XY, and no AZF gene deletion was detected. WES and Sanger sequencing detected compound heterozygous variants of the MOV10L1 gene, including a c.345C>A (p.C115X) nonsense variant and a c.3323C>T (p.T1108I) missense variant, with the former being unreported previously. HE staining showed only Sertoli cells in the seminiferous tubules, confirming the diagnosis of SCOS. Immunohistochemical staining revealed absent MOV10L1 protein expression in the testicular tissue. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the c.345C>A (p.C115X) was classified as a pathogenic variant (PVS1+PM2_Supporting+PP4), while the c.3323C>T (p.T1108I) was deemed variant of uncertain significance (PM2_Supporting+PP3_Supporting+PP4). Bioinformatics analysis demonstrated that c.345C>A (p.C115X) may cause premature termination of protein translation, while c.3323C>T (p.T1108I) may disrupt the hydrophobicity of the RNA helicase domain, reducing the active pocket volume and decreasing its affinity for MILI protein. CONCLUSION: This study has diagnosed a case of SCOS due to compound heterozygous variants of the MOV10L1 gene, which also enriched its mutational spectrum.

Humans↗
PubMed2026

Cohesin variants associated with human reproductive and developmental disorders.

The cohesin complex is an evolutionarily conserved multi-subunit protein assembly essential for sister chromatid cohesion, meiotic recombination, DNA double-strand break repair, and transcriptional regulation. Pathogenic variants in its subunits are implicated in a spectrum of reproductive and developmental disorders, including non-obstructive azoospermia, premature ovarian insufficiency, reproductive aging, aneuploidy, Cornelia de Lange syndrome, Roberts syndrome, cancer, and neuropsychiatric disease. Consequently, identifying cohesin mutations is a priority for precision diagnostics and personalized medicine. This review systematically summarizes the cohesin variants linked to these pathologies, exploring their molecular mechanisms and clinical manifestations. A deeper understanding of these variants is crucial not only for deciphering disease etiology but also for guiding the development of targeted diagnostic strategies and therapeutic interventions, ultimately improving patient management and outcomes.

Humans↗
PubMed2024

Diverse phenotypes and fertility outcomes of patients with androgen insensitivity syndrome in a Chinese family harboring identical AR gene variant.

BACKGROUND: Androgen insensitivity syndrome (AIS) is a rare genetic disorder characterized by resistance to androgens, mainly due to mutations in the androgen receptor (AR) gene. It can manifest as complete AIS, partial AIS and mild AIS. While there have been studies linking specific AR gene mutations to AIS phenotypes, different clinical AIS phenotypes are also reported in patients with the same AR gene mutation. So far, the precise correlations between phenotypes and genotypes remain incompletely understood. METHODS: We conducted a thorough investigation involving four patients diagnosed with different types of AIS from a single Chinese family. Clinical manifestations, laboratory examinations, and fertility outcomes were well-documented. Furthermore, we performed genetic sequencing to detect possible pathogenetic variants. RESULTS: Whole exome sequencing identified a hemizygous missense variant (c.2263T > C; p.Phe755Leu) of AR gene in all four affected patients with different degrees of undermasculinisation and heterogeneous spermatogenesis. The proband, diagnosed with partial AIS, opted for treatment with donated sperm due to non-obstructive azoospermia, while their older sibling, diagnosed with complete AIS, was raised as a girl. His two maternal uncles were both diagnosed with mild AIS, the older uncle fathered two girls naturally, whereas the younger uncle utilized assisted reproductive technology to conceive a boy because of severe oligoasthenozoospermia. CONCLUSION: Our study first identified the same AR variant (c.2263T > C;p.Phe755Leu) in four affected patients displaying highly diverse phenotypes of AIS and fertility outcomes, thereby significantly expanding the phenotypic spectrum of AIS. Notably, we presented a clear insight into different fertility outcomes of AIS patients with identical AR (c.2263T > C;p.Phe755Leu) variant, which provided reliable evidence that males harboring this variant may obtain biological offspring naturally or in combination with assisted reproductive technology. Furthermore, our study underscored the potential role of androgen concentration in shaping the phenotypic diversity of AIS, warranting further investigation.

Adult↗