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Veterinary World Mar 2020Fertility is the most important aspect in the efforts to increase livestock populations. Protamine and various proteins in sperm and seminal plasma are the results of... (Review)
Review
Fertility is the most important aspect in the efforts to increase livestock populations. Protamine and various proteins in sperm and seminal plasma are the results of the molecular analysis which can be used as a marker of fertility. Each of the proteins plays an important role in the normal function of sperm, starting from the formation of sperm structure, motility, capacitation, cell protection, acrosome reactions, successful fertilization, egg activation, and embryonic development. Finally, these molecular components can be a marker of fertility and can help to diagnose the cases of infertility/subfertility in livestock in the field.
PubMed: 32367964
DOI: 10.14202/vetworld.2020.556-562 -
Molecular Pharmaceutics Oct 2014RNA interference (RNAi) is an endogenous process in which small noncoding RNAs, including small interfering RNAs (siRNAs) and microRNAs (miRNAs), post-transcriptionally... (Review)
Review
RNA interference (RNAi) is an endogenous process in which small noncoding RNAs, including small interfering RNAs (siRNAs) and microRNAs (miRNAs), post-transcriptionally regulate gene expressions. In general, siRNA and miRNA/miRNA mimics are similar in nature and activity except their origin and specificity. Although both siRNAs and miRNAs have been extensively studied as novel therapeutics for a wide range of diseases, the large molecular weight, anionic surface charges, instability in blood circulation, and intracellular trafficking to the RISC after cellular uptake have hindered the translation of these RNAs from bench to clinic. As a result, a great variety of delivery systems have been investigated for safe and effective delivery of small noncoding RNAs. Among these systems, peptides, especially cationic peptides, have emerged as a promising type of carrier due to their inherent ability to condense negatively charged RNAs, ease of synthesis, controllable size, and tunable structure. In this review, we will focus on three major types of cationic peptides, including poly(l-lysine) (PLL), protamine, and cell penetrating peptides (CPP), as well as peptide targeting ligands that have been extensively used in RNA delivery. The delivery strategies, applications, and limitations of these cationic peptides in siRNA/miRNA delivery will be discussed.
Topics: Lysine; MicroRNAs; Peptides; RNA, Small Interfering; RNA, Small Untranslated
PubMed: 25157701
DOI: 10.1021/mp500426r -
Andrology Nov 2022Varicocoele is a common risk factor associated with reduced male fertility potential. The current understanding of varicocoele pathophysiology does not completely... (Review)
Review
BACKGROUND
Varicocoele is a common risk factor associated with reduced male fertility potential. The current understanding of varicocoele pathophysiology does not completely explain the clinical manifestation of infertility. The present treatment options such as antioxidant supplementation and varicocoelectomy only help ≈35% of men to achieve spontaneous pregnancy.
OBJECTIVE
This review aims to summarize the available knowledge on cellular and molecular alterations implicated to varicocoele-associated male infertility and also highlights the new knowledge generated by "omics" technologies.
MATERIALS AND METHODS
PubMed, MEDLINE, Cochrane and Google Scholar databases are searched using different combinations of keywords (varicocoele, infertile/fertile men with varicocoele, cellular changes, molecular mechanisms, proteome, epigenome, transcriptome and metabolome). A total of 229 relevant human and animal studies published till 2021 were included in this review.
RESULTS
Current understanding advocates oxidative stress (OS) as a major contributory factor to varicocoele-associated male infertility. Excessive OS causes alteration in testicular microenvironment and sperm DNA fragmentation, which further contributes to infertility. Molecular and omics studies have identified several promising biomarkers such as AAMP, SPINT1, MKI67 (genetic markers), sperm quality and function related protein markers, global sperm DNA methylation level (epigenetic marker), Hspa2, Protamine, Gadd7, Dynlt1 and Beclin1 (mRNA markers), PRDX2, HSPA, APOA2, YKL40 (seminal protein markers), total choline and PHGDH (metabolic markers).
DISCUSSION
Mature spermatozoa harbours a plethora of molecular information in form of proteome, epigenome and transcriptome, which could provide very important clues regarding pathophysiology of varicocoele-associated infertility. Recent molecular and omics studies in infertile men with varicocoele have identified several promising biomarkers. Upon further validation with larger and well-defined studies, some of these biomarkers could aid in varicocoele management.
CONCLUSION
The present evidences suggest that inclusion of OS and sperm DNA fragmentation tests could be useful to the diagnostic workup for men with varicocoele. Furthermore, including precise molecular markers may assist in diagnostics and prognostics of varicocoele-associated male infertility.
Topics: Antioxidants; Beclin-1; Chitinase-3-Like Protein 1; Choline; Dyneins; Genetic Markers; Humans; Infertility, Male; Male; Protamines; Proteome; RNA, Messenger; Semen; Spermatozoa; Varicocele
PubMed: 36040837
DOI: 10.1111/andr.13278 -
Current Opinion in Cell Biology Apr 2022The sperm genome is tightly packed into a minimal volume of sperm nuclei. Sperm chromatin is highly condensed by protamines (PRMs) after histone-protamine replacement,... (Review)
Review
The sperm genome is tightly packed into a minimal volume of sperm nuclei. Sperm chromatin is highly condensed by protamines (PRMs) after histone-protamine replacement, and the majority of the sperm genome forms a nucleo-protamine structure, namely, the PRM-DNA complex. The outline of sperm chromatin structure was proposed 30 years ago, and the details have been explored by approaches from several independent research fields including male reproduction and infertility, DNA biopolymer, and most recently, genome-wide sequence-based approaches. In this review, the history of research on sperm chromatin structure is briefly described, and the progress of recent related studies is summarized to obtain a more integrated view for the sperm chromatin, an extremely compacted "black box."
Topics: Chromatin; Chromatin Assembly and Disassembly; DNA; Humans; Male; Protamines; Spermatozoa
PubMed: 35344802
DOI: 10.1016/j.ceb.2022.102075 -
Frontiers in Pharmacology 2022Protamine can decrease the risk of hemorrhage during carotid recanalization. However, it may cause severe side effects. There is no consensus on the safety and efficacy... (Review)
Review
Protamine can decrease the risk of hemorrhage during carotid recanalization. However, it may cause severe side effects. There is no consensus on the safety and efficacy of protamine during surgery. Thus, we conduct a comprehensive review and meta-analysis to compare the differences between the protamine and the no-protamine group. We systematically obtained literature from Medline, Google Scholar, Cochrane Library, and PubMed electronic databases. All four databases were scanned from 1937 when protamine was first adopted as a heparin antagonist until February 2021. The reference lists of identified studies were manually checked to determine other eligible studies that qualify. The articles were included in this meta-analysis as long as they met the criteria of PICOS; conference or commentary articles, letters, case report or series, and animal observation were excluded from this study. The Newcastle-Ottawa Quality Assessment Scale and Cochrane Collaboration's tool are used to assess the risk of bias of each included observational study and RCT, respectively. Stata version 12.0 statistical software (StataCorp LP, College Station, Texas) was adopted as statistical software. When < 50%, we consider that the data have no obvious heterogeneity, and we conduct a meta-analysis using the fixed-effect model. Otherwise, the random-effect model was performed. A total of 11 studies, consisting of 94,618 participants, are included in this study. Our analysis found that the rate of wound hematoma had a significant difference among protamine and no-protamine patients (OR = 0.268, 95% CI = 0.093 to 0.774, = 0.015). Furthermore, the incidence of hematoma requiring re-operation (0.7%) was significantly lower than that of patients without protamine (1.8%). However, there was no significant difference in the incidence of stroke, wound hematoma with hypertension, transient ischemic attacks (TIA), myocardial infarction (MI), and death. Among included participants undergoing recanalization, the use of protamine is effective in reducing hematoma without increasing the risk of having other complications. Besides, more evidence-based performance is needed to supplement this opinion due to inherent limitations.
PubMed: 35281915
DOI: 10.3389/fphar.2022.796329 -
Journal of Materials Science. Materials... Apr 2022Calcium phosphates are key biomaterials in dental treatment and bone regeneration. Biomaterials must exhibit antibacterial properties to prevent microbial infection in...
Calcium phosphates are key biomaterials in dental treatment and bone regeneration. Biomaterials must exhibit antibacterial properties to prevent microbial infection in implantation frameworks. Previously, we developed various types of calcium phosphate powders (amorphous calcium phosphate, octacalcium phosphate (OCP), dicalcium phosphate anhydrate, and hydroxyapatite) with adsorbed protamine (which is a protein with antibacterial property) and confirmed their antibacterial property. In this study, as foundational research for the development of novel oral care materials, we synthesized calcium phosphate composite powders from three starting materials: i) OCP, which intercalates organic compounds, ii) protamine, which has antibacterial properties, and iii) F ion, which promotes the formation of apatite crystals. Through investigating the preparation concentration of the F ions and their loading into OCP, it was found that more F ion could be loaded at higher concentrations regardless of the loading method. It was also observed that the higher the preparation concentration, the more the OCP converted to fluorapatite. The synthesized calcium phosphate composite powders were evaluated for biocompatibility through proliferation of MG-63 cells, with none of the powders exhibiting any growth inhibition. Antimicrobial tests showed that the calcium phosphate composite powders synthesized with protamine and F ion by precipitation had enhanced antimicrobial properties than those synthesized by protamine adsorption. Thus, the calcium phosphate composite powder prepared from OCP, protamine, and F ion forms the basis for promising antimicrobial biomaterials. Graphical abstract.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Calcium Phosphates; Fluorides; Powders; Protamines
PubMed: 35362837
DOI: 10.1007/s10856-022-06656-5 -
Nature Structural & Molecular Biology Aug 2023Conventional dogma presumes that protamine-mediated DNA compaction in sperm is achieved by electrostatic interactions between DNA and the arginine-rich core of...
Conventional dogma presumes that protamine-mediated DNA compaction in sperm is achieved by electrostatic interactions between DNA and the arginine-rich core of protamines. Phylogenetic analysis reveals several non-arginine residues conserved within, but not across species. The significance of these residues and their post-translational modifications are poorly understood. Here, we investigated the role of K49, a rodent-specific lysine residue in protamine 1 (P1) that is acetylated early in spermiogenesis and retained in sperm. In sperm, alanine substitution (P1(K49A)) decreases sperm motility and male fertility-defects that are not rescued by arginine substitution (P1(K49R)). In zygotes, P1(K49A) leads to premature male pronuclear decompaction, altered DNA replication, and embryonic arrest. In vitro, P1(K49A) decreases protamine-DNA binding and alters DNA compaction and decompaction kinetics. Hence, a single amino acid substitution outside the P1 arginine core is sufficient to profoundly alter protein function and developmental outcomes, suggesting that protamine non-arginine residues are essential for reproductive fitness.
Topics: Animals; Male; Mice; Amino Acids; Arginine; Chromatin; DNA; Genetic Fitness; Phylogeny; Protamines; Semen; Sperm Motility; Spermatozoa
PubMed: 37460896
DOI: 10.1038/s41594-023-01033-4 -
Molecules (Basel, Switzerland) Jan 2024Protamine is a cationic peptide derived from fish sperm and has several important functional properties: antibacterial properties, acting as a carrier for injectable...
Protamine is a cationic peptide derived from fish sperm and has several important functional properties: antibacterial properties, acting as a carrier for injectable insulin and as a heparin antagonist, combatting fatigue, etc. Thus, it has been widely used in medicinal applications and food products. Cultured is a type of pufferfish with a delicious taste that is popular in China, and its production is increasing significantly. Therefore, protamine was extracted via acid extraction from the sperm of and further isolated and purified via sephadex gel chromatography, ion exchange chromatography, and desalination chromatography. Furthermore, the physicochemical properties of protamine were investigated. The results showed that the sperm of the cultured were non-toxic, and the extracted and purified protamine had high contents of arginine (36.90%) and lysine (27.02%), respectively. The secondary structure of protamine was mainly β-folded and irregularly curled. Additionally, protamine exhibited high thermal stability with a denaturation temperature of 176 °C. This study would provide a theoretical basis for the structural analysis, bioactivity, and resource development of pufferfish protamine and help to promote the development of the pufferfish industry.
Topics: Male; Animals; Takifugu; Protamines; Semen; Heparin Antagonists; Anti-Bacterial Agents
PubMed: 38202846
DOI: 10.3390/molecules29010263 -
Animal Reproduction Science Mar 2023Although previous studies have examined the relationship between the sperm DNA fragmentation index and fertility in stallions, other aspects of chromatin structure or...
Although previous studies have examined the relationship between the sperm DNA fragmentation index and fertility in stallions, other aspects of chromatin structure or packaging and fertility have not been explored. In the present study, relationships between fertility and DNA fragmentation index, protamine deficiency, total thiols, free thiols and disulfide bonds in stallion spermatozoa were investigated. Ejaculates (n = 36) were collected from 12 stallions and extended to prepare semen doses for insemination. One dose from each ejaculate was sent to the Swedish University of Agricultural Sciences. Aliquots of semen were stained for flow cytometry with acridine orange for the Sperm Chromatin Structure Assay (DNA fragmentation Index, %DFI), with chromomycin A3 (CMA) for protamine deficiency, and with monobromobimane (mBBr) for detection of total and free thiols and disulfide bonds. Per season pregnancy rates after insemination were obtained. Mixed linear models were used to analyze data. Negative correlations were found between pregnancy rate and %DFI (r = -0.35, P < 0.03) and pregnancy rate and free thiols (r = -0.60, P < 0.0001). Furthermore, there were positive correlations between total thiols and disulfide bonds (r = 0.95, P < 0.0001), and protamine and disulfide bonds (r = 0.4100, P < 0.01986). Since chromatin integrity, protamine deficiency and packaging were all associated with fertility, a combination of these factors could be used as a biomarker of fertility when assessing ejaculates.
Topics: Pregnancy; Female; Male; Animals; Horses; Chromatin; Semen; Biofilms; DNA Fragmentation; Bioreactors; Fertility; Spermatozoa; Protamines; Sulfhydryl Compounds; Disulfides
PubMed: 36801727
DOI: 10.1016/j.anireprosci.2023.107200 -
ACS Omega Nov 2022The insulin-protamine interaction is at the core of the mode of action in many insulin formulations (Zn + insulin + protamine) and to treat diabetes, in which protamine...
The insulin-protamine interaction is at the core of the mode of action in many insulin formulations (Zn + insulin + protamine) and to treat diabetes, in which protamine is added to the stable form of hexameric insulin (Zn-insulin). However, due to the unavailability of quantitative data and a high-resolution structure, the binding mechanism of the insulin-protamine complex remains unknown. In this study, it was observed that Zn-insulin experiences destabilization as observed by the loss of secondary structure in circular dichroism (CD), and reduction in thermal stability in melting study, upon protamine binding. In isothermal titration calorimetry (ITC), it was found that the interactions were mostly enthalpically driven. This is in line with the positive Δ value (+880 cal mol), indicating the role of hydrophilic interactions in the complex formation, with the exposure of hydrophobic residues to the solvent, which was firmly supported by the 8-anilino-1-naphthalene sulfonate (ANS) binding study. The stoichiometry () value in ITC suggests the multiple insulin molecules binding to the protamine chain, which is consistent with the picture of the condensation of insulin in the presence of protamine. Atomic force microscopy (AFM) suggested the formation of a heterogeneous Zn-insulin-protamine complex. In fluorescence, Zn-insulin experiences strong Tyr quenching, suggesting that the location of the protamine-binding site is near Tyr, which is also supported by the molecular docking study. Since Tyr is critical in the stabilization of insulin self-assembly, its interaction with protamine may impair insulin's self-association ability and thermodynamic stability while at the same time promoting its flexible conformation desired for better biological activity.
PubMed: 36406544
DOI: 10.1021/acsomega.2c04419