Sperm acquire epididymis-derived proteins through epididymosomes

Human Reproduction, Journal Year: 2022, Volume and Issue: 37(4), P. 651 - 668

Published: Jan. 14, 2022

Abstract STUDY QUESTION Are epididymosomes implicated in protein transfer from the epididymis to spermatozoa? SUMMARY ANSWER We characterized contribution of epididymal secretions sperm proteome and demonstrated that acquire proteins through epididymosomes. WHAT IS KNOWN ALREADY Testicular are immature cells unable fertilize an oocyte. After leaving testis, transit along motility fertilizing abilities. It is well known marked changes profile occur during maturation. Since a transcriptional translational inert cell, previous studies have shown incorporate proteins, RNA lipids extracellular vesicles (EVs), released by epithelial lining male reproductive tract. DESIGN, SIZE, DURATION examined post-testicular maturation spermatozoa, via production EVs named epididymosomes, cells. An integrative analysis using both human mouse data was performed identify with potential epididymis-derived origin. Testes epididymides adult humans (n = 9) mice 3) were used experimentally validate tissue localization four selected high-resolution confocal microscopy. Mouse co-incubated carboxyfluorescein succinimidyl ester (CFSE)-labeled 4 mice), visualized PARTICIPANTS/MATERIALS, SETTING, METHODS Adult (12-week-old) C57BL/CBAF1 wild-type for validation purposes. obtained processed immunofluorescence. cauda segment. Fluorescent after labeling CFSE dye followed epididymosome isolation density cushion. Immunofluorescence following co-incubation vitro. High-resolution microscopy 3D image reconstruction visualize sperm-epididymosomes interactions. MAIN RESULTS AND THE ROLE OF CHANCE Through silico analysis, we first identified 25 putative origin conserved spermatozoa. From those, (SLC27A2, EDDM3B, KRT19 WFDC8) validated SLC27A2, WFDC8 all detected epididymis, absent seminiferous tubules. found region-specific expression patterns these throughout epididymides. In addition, while principal clear (CCs), SLC27A2 exclusively expressed CCs. Finally, showed CFSE-fluorescently labeled interact vitro about 12–36% contain targeted LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION The sample size limited our results descriptive. analyses solely model due difficulties obtaining luminal fluid samples. Alternatively, ejaculated seminal could not be because already contacted fluids secreted accessory sex glands, other addition such as abundant prostate-derived EVs. WIDER IMPLICATIONS FINDINGS Our findings indicate capable providing spermatozoa new set modulate and, subsequently, participate Additionally, provide further evidence novel role CCs production. Identifying mechanisms which mature their fertilization would, ultimately, lead better understanding health may help therapeutic strategies improve infertility. FUNDING/COMPETING INTEREST(S) This work supported Spanish Ministry Economy Competitiveness (Ministerio de Economía y Competividad; fondos FEDER ‘una manera hacer Europa’ PI13/00699 PI16/00346 R.O.; Sara Borrell Postdoctoral Fellowship, Acción Estratégica en Salud, CD17/00109 J.C.), National Institutes Health (grants HD040793 HD069623 S.B., grant HD104672-01 M.A.B.), Education, Culture Sports Educación, Cultura Deporte para la Formación Profesorado Universitario, FPU15/02306 F.B.), Lalor Foundation Fellowship (to F.B. Government Catalonia (Generalitat Catalunya, pla estratègic recerca i innovació salut, PERIS 2016-2020, SLT002/16/00337 M.J.), Fundació Universitària Agustí Pedro Pons American Society Biochemistry Molecular Biology (PROLAB Award ASBMB/IUBMB/PABMB F.B.). Confocal transmission electron Microscopy Core facility Massachusetts General Hospital (MGH) Center Systems Biology/Program Membrane receives support Boston Area Diabetes Endocrinology Research (BADERC) award DK57521 Study Inflammatory Bowel Disease DK43351. Zeiss LSM800 microscope acquired NIH Shared Instrumentation Grant S10-OD-021577-01. authors no conflicts interest declare.

Language: Английский

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Lipid nanovesicles for biomedical applications: ‘What is in a name’?

Progress in Lipid Research, Journal Year: 2021, Volume and Issue: 82, P. 101096 - 101096

Published: April 1, 2021

Language: Английский

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Seminal exosomes – An important biological marker for various disorders and syndrome in human reproduction

Saudi Journal of Biological Sciences, Journal Year: 2021, Volume and Issue: 28(6), P. 3607 - 3615

Published: March 18, 2021

Exosomes are nano-sized membrane vesicles, secreted by different types of cells into the body's biological fluids. They found in abundance semen as compared to other contain a cargo lipid molecules, proteins, phospholipids, cholesterol, mRNAs, and miRNAs. Each molecule seminal exosomes (SE) has potential role male reproduction for childbirth. Many candidates available within that can be used diagnostic markers various diseases or syndromes associated with reproduction. Also these exospmes play major female reproductive tract effective fertilization.

Language: Английский

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Putative adverse outcome pathways for silver nanoparticle toxicity on mammalian male reproductive system: a literature review

Particle and Fibre Toxicology, Journal Year: 2023, Volume and Issue: 20(1)

Published: Jan. 5, 2023

Abstract Background Adverse outcome pathways (AOPs) are conceptual frameworks that organize knowledge about biological interactions and toxicity mechanisms. They present a sequence of events commencing with initial interaction(s) stressor, which defines the perturbation in system (molecular initiating event, MIE), dependent series key (KEs), ending an adverse (AO). AOPs have recently become subject intense studies view to better understand mechanisms nanomaterial (NM) toxicity. Silver nanoparticles (Ag NPs) one most explored nanostructures extensively used various application. This, turn, has increased potential for Ag NPs environments, human health. The aim this study was construct putative (pAOP) related reproductive NPs, order lay groundwork comprehension affecting both undesired (against cell) expected microorganisms). Methods PubMed Scopus were systematically searched peer-reviewed examining NPs. quality selected assessed through ToxRTool. Eventually, forty-eight published between 2005 2022 identify impact on function male. endpoints, measurements, results extracted from these studies. Where possible, endpoints assigned KE AO using expert judgment. Then, KEs classified at each major level organization. Results We identified impairment intracellular SH-containing biomolecules, cellular antioxidants, as MIE, subsequent defined ROS accumulation, mitochondrial damage, DNA damage lipid peroxidation, apoptosis, reduced production hormones sperm. These successive may result impaired male fertility Conclusion This research recapitulates schematically represents complex literature data gathered different levels propose pAOP induced by AgNPs. development specific NMs should be encouraged provide new insights gain understanding NP

Language: Английский

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Human Male Genital Tract Microbiota

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 6939 - 6939

Published: April 8, 2023

The human body is vastly colonised by microorganisms, whose impact on health increasingly recognised. genital tract hosts a diverse microbiota, and an increasing number of studies the male microbiota suggest that bacteria have role in infertility pathological conditions, such as prostate cancer. Nevertheless, this research field remains understudied. study bacterial colonisation highly impacted invasive nature sampling low abundance microbiota. Therefore, most relied analysis semen to describe (MGT), which was thought be sterile. aim narrative review present results used next-generation sequencing (NGS) profile patterns different anatomical compartments critically highlight their findings weaknesses. Moreover, we identified potential axes may crucial for our understanding its pathophysiology.

Language: Английский

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From spermatogenesis to fertilisation: the role of melatonin on ram spermatozoa

Domestic Animal Endocrinology, Journal Year: 2025, Volume and Issue: 91, P. 106916 - 106916

Published: Jan. 14, 2025

Language: Английский

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Epigenetic transgenerational inheritance, gametogenesis and germline development†

Biology of Reproduction, Journal Year: 2021, Volume and Issue: 105(3), P. 570 - 592

Published: April 30, 2021

Abstract One of the most important developing cell types in any biological system is gamete (sperm and egg). The transmission phenotypes optimally adapted physiology to subsequent generations large part controlled by gametogenesis. In contrast genetics, environment actively regulates epigenetics impact phenotype cellular systems. integration genetics critical for all developmental biology systems at organism level. current review focused on role during gametogenesis both spermatogenesis male oogenesis female. stages from initial primordial germ through mature sperm egg are presented. How environmental factors can influence epigenetic transgenerational inheritance phenotypic physiological change reviewed.

Language: Английский

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The cell biology of fertilization: Gamete attachment and fusion

The Journal of Cell Biology, Journal Year: 2021, Volume and Issue: 220(10)

Published: Aug. 30, 2021

Fertilization is defined as the union of two gametes. During fertilization, sperm and egg fuse to form a diploid zygote initiate prenatal development. In mammals, fertilization involves multiple ordered steps, including acrosome reaction, zona pellucida penetration, sperm–egg attachment, membrane fusion. Given success in vitro one would think that mechanisms are understood; however, precise details for many steps remain mystery. Recent studies using genetic knockout mouse models structural biology providing valuable insight into molecular basis attachment Here, we review cell specifically summarizing data from recent functional provide insights interactions involved human gamete

Language: Английский

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Regulatory T cells play a crucial role in maintaining sperm tolerance and male fertility

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(37)

Published: Sept. 7, 2023

Regulatory T cells (Tregs) modulate tissue homeostatic processes and immune responses. Understanding tissue-Treg biology will contribute to developing precision-targeting treatment strategies. Here, we show that Tregs maintain the tolerogenic state of testis epididymis, where sperm are produced mature. We found Treg depletion induces severe autoimmune orchitis epididymitis, manifested by an exacerbated cell infiltration [CD4 cells, monocytes, mononuclear phagocytes (MPs)] development antisperm antibodies (ASA). In Treg-depleted mice, MPs increased projections toward epididymal lumen as well invading lumen. ASA-bound enhance agglutination might facilitate phagocytosis. Tolerance breakdown impaired epithelial function altered extracellular vesicle cargo, both which play crucial roles in acquisition fertilizing ability subsequent embryo development. The affected mice had reduced number motility fertility defects. Deciphering these immunoregulatory mechanisms may help design new strategies treat male infertility, identify potential targets for immunocontraception.

Language: Английский

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Sperm RNA Payload: Implications for Intergenerational Epigenetic Inheritance

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5889 - 5889

Published: March 20, 2023

There is mounting evidence that ancestral life experiences and environment can influence phenotypes in descendants. The parental regulates offspring potentially via modulating epigenetic marks the gametes. Here, we review examples of across-generational inheritance paternal environmental effects current understanding role small RNAs such inheritance. We discuss recent advances revealing RNA payload sperm how conditions modulate RNAs. Further, potential mechanism by focusing on RNA-mediated regulation early embryonic gene expression its influencing phenotypes.

Language: Английский

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