LRRC23 truncation impairs radial spoke 3 head assembly and sperm motility underlying male infertility

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Dec. 13, 2023

Radial spokes (RS) are T-shaped multiprotein complexes on the axonemal microtubules. Repeated RS1, RS2, and RS3 couple central pair to modulate ciliary flagellar motility. Despite cell type specificity of substructures, their molecular components remain largely unknown. Here, we report that a leucine-rich repeat-containing protein, LRRC23, is an head component essential for its assembly motility in mammalian spermatozoa. From infertile male patients with defective sperm motility, identified splice site variant LRRC23 . A mutant mouse model mimicking this produces truncated at C-terminus fails localize tail, causing infertility due was previously proposed be ortholog RS stalk protein RSP15. However, found purified recombinant interacts RSPH9, which abolished by C-terminal truncation. Evolutionary structural comparison also shows LRRC34, not RSP15 ortholog. Cryo-electron tomography clearly revealed absence sperm-specific RS2-RS3 bridge structure Our study provides new insights into function spermatozoa pathogenicity underlying reduced human males.

Language: Английский

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Association between chromosome 6p21 translocation and asthenozoospermia: A retrospective, observational study

Medicine, Journal Year: 2023, Volume and Issue: 102(27), P. e34318 - e34318

Published: July 7, 2023

Asthenozoospermia (AZS) is the commonest cause of male-related infertility. The patients with AZS easily exhibit infertility, their wives having spontaneous miscarriages or seeking assisted reproductive treatment. Reciprocal chromosomal translocation (RCT) an important chromosome structural abnormality and has been reported to affect sperm motility. Genetic counseling for male RCT still a challenge. This study 4 carriers, which were 46,XY,t(1;6) (p36.1;p21), 46,XY,t (6;10) (p21;q11.2), (6;11) (p21;p15), (6;17) (p21;q21), respectively. association between 6p21 discussed, considering 19 published cases as well. In 6 available semen parameters in this study, all them diagnosed AZS. SLC26A8 gene DNAH8 located on are closely related by search using OMIM. For breakpoint, 72 pathogenic genes found through DECIPHER search. Gene ontology analysis showed that these target have several molecular functions strongly involved various biological processes. proteins expressed multiple cellular components. These results suggest breakpoint carriers may disrupt structure function genes, resulting reduced Karyotype should be recommended patients. Chromosomes breakpoints paid attention genetic

Language: Английский

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Identification of IQCH as a calmodulin-associated protein required for sperm motility in humans

iScience, Journal Year: 2023, Volume and Issue: 26(8), P. 107354 - 107354

Published: July 10, 2023

Sperm fertilization ability mainly relies on proper sperm progression through the female genital tract and capacitation, which involves phosphorylation signaling pathways triggered by calcium bicarbonate. We performed exome sequencing of an infertile asthenozoospermic patient identified truncating variants in MAP7D3, encoding a microtubule-associated protein, IQCH, protein unknown function with enzymatic features. demonstrate deleterious impact both transcripts proteins from patient. show that, vitro, spermatozoa could not induce cascades associated capacitation. also provide evidence for IQCH association calmodulin, well-established calcium-binding that regulates calmodulin kinase. Notably, we describe spatial distribution around axoneme, supporting its within flagella. Overall, our work highlights cumulative pathological gene mutations identifies as key required motility

Language: Английский

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Potentials of electron microscopic examination in the diagnosis of genetically determined disorders related to morphology and motility of human spermatozoa

BIO Web of Conferences, Journal Year: 2024, Volume and Issue: 100, P. 03017 - 03017

Published: Jan. 1, 2024

Despite infertility is known as a serious medical and social issue, commercial panels for the determination of genetically caused disorders morphology motility spermatozoa are not available in territory Eurasian Economic Union. Electron microscopic examination (EMIS) represents promising method that allows to visualize analyze structural anomalies at level which accessible by other methods. The study included transmission electron microscopy (TEM) spermatozoa. Native sperm was diluted fixed with 2.5% glutaraldehyde. Ultrathin sections were obtained on an UltraCut III microtome. Analysis performed magnifications x4000, x25000. Spermatozoa analyzed JEM-1011 microscope different identify general appearance, axonemal anomalies, chromatin nucleus, mitochondria. EMIS serves tool detailed analysis patients asthenozoospermia (AZS) teratozoospermia (TZS), their combination. data provide basis more accurate diagnosis personalized treatment approaches, contributing increased effectiveness overcoming infertility.

Language: Английский

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DNA methylation patterns in patients with asthenospermia and oligoasthenospermia

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

Published: June 17, 2024

Abstract Background Spermatogenesis is a highly regulated and complex process in which DNA methylation plays crucial role. This study aimed to explore the differential profiles sperm between patients with asthenospermia (AS) healthy controls (HCs), those oligoasthenospermia (OAS) HCs, AS OAS. Results Semen samples clinical data were collected from five AS, OAS, six age-matched HCs. Reduced representation bisulfite sequencing (RRBS) was performed identify differentially methylated regions (DMRs) cells among different types of A total 6520, 28,019, 16,432 DMRs detected HC, OAS groups, respectively. These predominantly located within gene bodies mapped 2868, 9296, 9090 genes respective groups. Of note, 12, 9, 8 each group closely associated spermatogenesis male infertility. Furthermore, BDNF, SMARCB1, PIK3CA, DDX27; RBMX SPATA17; ASZ1, CDH1, CHDH identified as strong candidate group, Meanwhile, GO analysis DMR-associated vs. HC groups revealed that protein binding, cytoplasm, transcription (DNA-templated) most enriched terms biological (BP), cellular component (CC), molecular function (MF), Likewise, both nucleus, BP, CC, MF, Finally, KEGG DMR-annotated these at promoters suggested metabolic pathways significantly across all three Conclusions The current results distinctive patterns particularly identification key infertility addition may contribute uncovering potential pathogenesis abnormal parameters.

Language: Английский

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Functional Analysis of Transmembrane Ion Flux and Transport in Sperm

Springer eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 293 - 316

Published: Jan. 1, 2024

Language: Английский

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Sperm Motility

Springer eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 61 - 101

Published: Jan. 1, 2024

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Voltage-Dependent Anion Channels in Male Reproductive Cells: Players in Healthy Fertility?

Biomolecules, Journal Year: 2024, Volume and Issue: 14(10), P. 1290 - 1290

Published: Oct. 12, 2024

Male infertility affects nearly 50% of infertile couples, with various underlying causes, including endocrine disorders, testicular defects, and environmental factors. Spermatozoa rely on mitochondrial oxidative metabolism for motility fertilization, mitochondria playing a crucial role in sperm energy production, calcium regulation, redox balance. Voltage-dependent anion channels (VDACs), located the outer membrane, regulate metabolite exchange, which are essential function. This review offers an updated analysis VDACs male reproductive system, summarizing recent advances understanding their expression patterns, molecular functions, regulatory mechanisms. Although have been widely studied other tissues, specific roles physiology still remain underexplored. Special attention is given to involvement VDAC2/3 isoforms, may influence function cells could be implicated fertility disorders. update provides comprehensive framework future research biology, underscoring significance as link between fertility.

Language: Английский

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Comparison of different processed products of Allium tuberosum Rottler for the treatment of mice asthenozoospermia

Translational Andrology and Urology, Journal Year: 2024, Volume and Issue: 13(10), P. 2209 - 2228

Published: Oct. 1, 2024

improves sexual function and is used in the treatment of impotence spermatorrhea. However, its chemical composition mechanism action remain unclear. This study investigates

Language: Английский

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Genetic Polymorphisms in Genes Associated with Mammalian Semen Quality Traits: A Review

Agriculture, Journal Year: 2024, Volume and Issue: 14(12), P. 2137 - 2137

Published: Nov. 25, 2024

Semen quality traits, including sperm morphology, shape, count, ejaculate volume, low percentage of motile spermatozoa in semen, and motility, play a crucial role male reproductive efficiency fertilization success. This review article highlighted the impact genetic polymorphisms genes on semen fertility traits mammalians. Single nucleotide (SNPs) these were associated with various abnormalities, such as abnormal flagella reduced impaired DNA integrity, altered antioxidant status, disrupted head–tail junction, spermatogenesis defects, testicular size, range disorders. comprehensive available literature offers significant insights into factors influencing which can contribute to development markers enhancement through assisted selective breeding programs.

Language: Английский

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