Long non-coding RNAs (lncRNAs) in spermatogenesis and male infertility

Reproductive Biology and Endocrinology, Journal Year: 2020, Volume and Issue: 18(1)

Published: Oct. 30, 2020

Abstract Background Long non-coding RNAs (lncRNAs) have a size of more than 200 bp and are known to regulate host crucial cellular processes like proliferation, differentiation apoptosis by regulating gene expression. While small noncoding (ncRNAs) such as miRNAs, siRNAs, Piwi-interacting been extensively studied in male germ cell development, the role lncRNAs spermatogenesis remains largely unknown. Objective In this article, we reviewed biology along with tools available for data analysis. Results conclusions Till date, three microarray four RNA-seq studies undertaken identify mouse testes or cells. These were done on pre-natal, post-natal, adult testis, different cells spermatogenesis. case humans, five populations, including two sperm, undertaken. We compared human common found 15 (LINC00635, LINC00521, LINC00174, LINC00654, LINC00710, LINC00226, LINC00326, LINC00494, LINC00535, LINC00616, LINC00662, LINC00668, LINC00467, LINC00608, LINC00658) show consistent differential expression across these studies. Some targets included CENPB, FAM98B, GOLGA6 family, RPGR, TPM2, GNB5, KCNQ10T1, TAZ, LIN28A, CDKN2B, CDKN2A, CDKN1A, CDKN1B, CDKN1C, EZH2, SUZ12, VEGFA genes. A lone study infertility identified 9879 differentially expressed (lnc32058, lnc09522, lnc98497) them showing specific high immotile sperm comparison normal motile sperm. few (Mrhl, Drm, Spga-lncRNAs, NLC1-C, HongrES2, Tsx, LncRNA-tcam1, Tug1, Tesra, AK015322, Gm2044, LncRNA033862) functionally validated their roles Apart from rodents sheep bull also potentially important number strong candidates further research

Language: Английский

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Sperm bauplan and function and underlying processes of sperm formation and selection

Physiological Reviews, Journal Year: 2021, Volume and Issue: 102(1), P. 7 - 60

Published: April 21, 2021

The spermatozoon is a highly differentiated and polarized cell, with two main structures: the head, containing haploid nucleus acrosomal exocytotic granule, flagellum, which generates energy propels cell; both structures are connected by neck. sperm’s aim to participate in fertilization, thus activating development. Despite this common bauplan function, there an enormous diversity structure performance of sperm cells. For example, mammalian spermatozoa may exhibit several head patterns overall lengths ranging from ∼30 350 µm. Mechanisms transport female tract, preparation for recognition interaction oocyte also show considerable variation. There has been much interest understanding origin diversity, evolutionary terms relation mechanisms underlying differentiation testis. Here, relationships between function examined at levels: first, analyzing selective forces that drive changes physiology understand adaptive values variation impact on male reproductive success second, examining cellular molecular formation testis explain how can give rise such wide array forms functions.

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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The Slingshot phosphatase 2 is required for acrosome biogenesis during spermatogenesis in mice

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

Published: March 21, 2023

The acrosome is a membranous organelle positioned in the anterior portion of sperm head and essential for male fertility. Acrosome biogenesis requires dynamic cytoskeletal shuttling vesicles toward nascent which regulated by series accessory proteins. However, much remains unknown about molecular basis underlying this process. Here, we generated Ssh2 knockout (KO) mice HA-tagged knock-in (KI) to define functions Slingshot phosphatase 2 (SSH2) spermatogenesis demonstrated that as regulator actin remodeling, SSH2 In KO males, was arrested at early spermatid stage with increased apoptotic index impaired characterized defective transport/fusion proacrosomal vesicles. Moreover, disorganized F-actin structures accompanied excessive phosphorylation COFILIN were observed testes mice. Collectively, our data reveal modulatory role through COFILIN-mediated remodeling indispensability fertility

Language: Английский

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Characterization of gonadal development phases and maturation mechanisms in male Pacific whiteleg shrimp (Litopenaeus vannamei)

Aquaculture, Journal Year: 2024, Volume and Issue: 584, P. 740669 - 740669

Published: Feb. 13, 2024

Language: Английский

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Whole Exome Sequencing and In Silico Analysis of Human Sertoli in Patients with Non-Obstructive Azoospermia

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(20), P. 12570 - 12570

Published: Oct. 20, 2022

Non-obstructive azoospermia (NOA) is a serious cause of male infertility. The Sertoli cell responds to androgens and takes on roles supporting spermatogenesis, which may This work aims enhance the genetic diagnosis NOA via discovery new hub genes implicated in human better assess odds successful sperm extraction according individual's genotype. Whole exome sequencing (WES) was done three patients find key involved NOA. We evaluated genome-wide transcripts (about 50,000 transcripts) by microarray between non-obstructive normal cells. analysis cases with different revealed that 32 were upregulated, expressions 113 downregulated versus case. For this purpose, Enrich Shiny GO, STRING, Cytoscape online evaluations applied predict functional molecular interactions proteins then recognize master pathways. enrichment demonstrated biological process (BP) terms "inositol lipid-mediated signaling", "positive regulation transcription RNA polymerase II", DNA-templated transcription" significantly changed upregulated differentially expressed (DEGs). BP investigation DEGs highlighted "mitotic cytokinesis", "regulation protein-containing complex assembly", "cytoskeleton-dependent "peptide metabolic process". Overrepresented function (MF) included "ubiquitin-specific protease binding", "protease "phosphatidylinositol trisphosphate phosphatase activity", "clathrin light chain binding". Interestingly, MF overexpression "ATPase inhibitor "glutathione transferase regulator activity". Our findings suggest these their interacting could help determine pathophysiologies germ abnormalities

Language: Английский

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Semen Proteomics of COVID-19 Convalescent Men Reveals Disruption of Key Biological Pathways Relevant to Male Reproductive Function

ACS Omega, Journal Year: 2022, Volume and Issue: 7(10), P. 8601 - 8612

Published: March 7, 2022

A considerable section of males suffered from COVID-19, with many experiencing long-term repercussions. Recovered have been documented to compromised fertility, albeit the mechanisms remain unclear. We investigated impact COVID-19 on semen proteome following complete clinical recovery using mass spectrometry. label-free quantitative proteomics study involved 10 healthy fertile subjects and 17 COVID-19-recovered men. With 1% false discovery rate >1 unique peptide stringency, MaxQuant analysis found 1099 proteins 8503 peptides. Of 48 differentially expressed between groups, 21 were downregulated 27 upregulated in males. The major pathways reproductive functions, such as sperm-oocyte recognition, testosterone response, cell motility regulation, adhesion extracellular matrix adhesion, endopeptidase activity, patients according bioinformatics analysis. Furthermore, targeted approach revealed significant downregulation semenogelin 1 prosaposin, two related male fertility. Therefore, we demonstrate alteration response thus disrupting function despite patient's remission. Hence, understand fertility-related biological processes triggered by this infection, a protracted evaluation consequences recovered men is warranted.

Language: Английский

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Sperm chromatin condensation: epigenetic mechanisms to compact the genome and spatiotemporal regulation from inside and outside the nucleus

Genes & Genetic Systems, Journal Year: 2022, Volume and Issue: 97(1), P. 41 - 53

Published: Feb. 1, 2022

Sperm chromatin condensation is a critical step in mammalian spermatogenesis to protect the paternal DNA from external damaging factors and acquire fertility. During condensation, various events proceed chronological order, independently or sequence, interacting with each other both inside outside nucleus support dramatic changes. Among these events, histone–protamine replacement, which concomitant acrosome biogenesis cytoskeletal alteration, most associated nuclear elongation. Failures of not only intranuclear but also extra-nuclear severely affect sperm shape state are subsequently linked infertility. This review focuses on non-nuclear that its effects, further discusses possible utility for clinical applications.

Language: Английский

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Cylicins are a structural component of the sperm calyx being indispensable for male fertility in mice and human

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

Published: March 23, 2023

Cylicins are testis-specific proteins, which exclusively expressed during spermiogenesis. In mice and humans, two Cylicins, the gonosomal X-linked Cylicin 1 (Cylc1/CYLC1) autosomal 2 (Cylc2/CYLC2) genes, have been identified. cytoskeletal proteins with an overall positive charge due to lysine-rich repeats. While localized in acrosomal region of round spermatids, they resemble a major component calyx within perinuclear theca at posterior part mature sperm nuclei. However, role spermiogenesis has not yet investigated. Here, we applied CRISPR/Cas9-mediated gene editing zygotes establish Cylc1- Cylc2-deficient mouse lines as model study function these proteins. Cylc1 deficiency resulted male subfertility, whereas Cylc2-/-, Cylc1-/yCylc2+/-, Cylc1-/yCylc2-/- males were infertile. Phenotypical characterization revealed that loss prevents proper assembly This results decreased epididymal counts, impaired shedding excess cytoplasm, severe structural malformations, ultimately resulting motility. Furthermore, exome sequencing identified infertile man hemizygous variant CYLC1 heterozygous CYLC2, displaying morphological abnormalities including absence acrosome. Thus, our highlights relevance importance for spermiogenic remodeling fertility human mouse, provides basis further studies on unraveling complex molecular interactions between required

Language: Английский

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Biomaterials for Testicular Bioengineering: How far have we come and where do we have to go?

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: March 16, 2023

Traditional therapeutic interventions aim to restore male fertile potential or preserve sperm viability in severe cases, such as semen cryopreservation, testicular tissue, germ cell transplantation and graft. However, these techniques demonstrate several methodological, clinical, biological limitations, that impact their results. In this scenario, reproductive medicine has sought biotechnological alternatives applied for infertility treatment, improve gamete preservation thus increase rates

Language: Английский

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