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Human Reproduction Update 2016Extracellular vesicles (EVs) are membrane-bound vesicles, found in biofluids, that carry and transfer regulatory molecules, such as microRNAs (miRNAs) and proteins, and... (Review)
Review
BACKGROUND
Extracellular vesicles (EVs) are membrane-bound vesicles, found in biofluids, that carry and transfer regulatory molecules, such as microRNAs (miRNAs) and proteins, and may mediate intercellular communication between cells and tissues. EVs have been isolated from a wide variety of biofluids, including plasma, urine, and, relevant to this review, seminal, follicular and uterine luminal fluid. We conducted a systematic search of the literature to review and present the currently available evidence on the possible roles of EVs in follicular growth, resumption of oocyte development and maturation (meiosis), sperm maturation, fertilization and embryo implantation.
METHODS
MEDLINE, Embase and Web of Science databases were searched using keywords pertaining to EVs, including 'extracellular vesicles', 'microvesicles', 'microparticles' and 'exosomes', combined with a range of terms associated with the period of development between fertilization and implantation, including 'oocyte', 'sperm', 'semen', 'fertilization', 'implantation', 'embryo', 'follicular fluid', 'epididymal fluid' and 'seminal fluid'. Relevant research articles published in English (both animal and human studies) were reviewed with no restrictions on publication date (i.e. from earliest database dates to July 2015). References from these articles were used to obtain additional articles.
RESULTS
A total of 1556 records were retrieved from the three databases. After removing duplicates and irrelevant titles, we reviewed the abstracts of 201 articles, which included 92 relevant articles. Both animal and human studies unequivocally identified various types of EVs in seminal, follicular and ULFs. Several studies provided evidence for the roles of EVs in these biofluids. In men, EVs in seminal fluid were linked with post-testicular sperm maturation, including sperm motility acquisition and reduction of oxidative stress. In women, EVs in follicular fluid were shown to contain miRNAs with potential roles in follicular growth, resumption of oocyte meiosis, steroidogenesis and prevention of polyspermy after fertilization. EVs were also detected in the media of cultured embryos, suggesting that EVs released from embryos and the uterus may mediate embryo-endometrium cross-talk during implantation. It is important to note that many of the biologically plausible functions of EVs in reproduction discussed in the current literature have not yet been substantiated by conclusive experimental evidence.
CONCLUSIONS
A detailed understanding of the contributions of EVs in the series of events from gametogenesis to fertilization and then on to implantation, in both normal and pathological cases, may enable the development of valuable tools to advance reproductive health. Because of the early stage of the field, it is unsurprising that the current literature includes not only growing experimental evidence, but also as-yet unproven hypotheses pertaining to the roles of EVs in key reproductive processes. In this review, we present a comprehensive survey of the rapidly expanding literature on this subject, highlighting both relevant findings and gaps in knowledge.
Topics: Animals; Cell Communication; Embryo Implantation; Extracellular Vesicles; Female; Fertilization; Humans; Male; Oocytes; Oogenesis; Pregnancy; Semen; Spermatogenesis
PubMed: 26663221
DOI: 10.1093/humupd/dmv055 -
Biomolecules Jun 2017Various studies have revealed the effects of vitamin B12, also named cobalamin, on semen quality and sperm physiology; however, these studies collectively are still... (Review)
Review
Various studies have revealed the effects of vitamin B12, also named cobalamin, on semen quality and sperm physiology; however, these studies collectively are still unsummarized. Here, we systematically discuss and summarize the currently understood role of vitamin B12 on semen quality and sperm physiology. We searched the Web of Science, PubMed, and Scopus databases for only English language articles or abstracts from September 1961 to March 2017 (inclusive) using the key words "vitamin B12" and "cobalamin" versus "sperm". Certain relevant references were included to support the empirical as well as the mechanistic discussions. In conclusion, the mainstream published work demonstrates the positive effects of vitamin B12 on semen quality: first, by increasing sperm count, and by enhancing sperm motility and reducing sperm DNA damage, though there are a few in vivo system studies that have deliberated some adverse effects. The beneficial effects of vitamin B12 on semen quality may be due to increased functionality of reproductive organs, decreased homocysteine toxicity, reduced amounts of generated nitric oxide, decreased levels of oxidative damage to sperm, reduced amount of energy produced by spermatozoa, decreased inflammation-induced semen impairment, and control of nuclear factor-κB activation. However, additional research, mainly clinical, is still needed to confirm these positive effects.
Topics: Animals; Humans; Semen; Semen Analysis; Vitamin B 12
PubMed: 28598359
DOI: 10.3390/biom7020042 -
Theriogenology Oct 2019Recently numerous proteomic approaches have been undertaken to identify sperm and seminal plasma (SP) proteins that can be used as potential biomarkers for sperm... (Review)
Review
Recently numerous proteomic approaches have been undertaken to identify sperm and seminal plasma (SP) proteins that can be used as potential biomarkers for sperm function, including fertilization ability. This review aims firstly to briefly introduce the proteomic technologies and workflows that can be successfully applied for sperm and SP proteomic analysis. Secondly, we summarize the current knowledge about boar SP and the sperm proteome, focusing mainly on its relevance to sperm preservation procedures (liquid storage or cryopreservation) and their outcomes in terms of sperm function and fertility.
Topics: Animals; Male; Proteomics; Semen; Semen Preservation; Spermatozoa; Swine
PubMed: 31208776
DOI: 10.1016/j.theriogenology.2019.05.033 -
Animal Reproduction Science Dec 2022Animal studs that provide extended semen for breeding have a significant contribution to reproductive outcomes. This report highlights several biological and chemical...
Animal studs that provide extended semen for breeding have a significant contribution to reproductive outcomes. This report highlights several biological and chemical contaminants in extended semen that were found to be the causative agent for disturbances to herd reproductive performance, along with the diagnostic approach used in contaminant identification. Biological contaminants of concern include bacteria, viruses, and molds. From our investigations, opportunistic bacteria of mammalian and purified water origin appeared to be the most common biologic contaminant in stud operations. Chemical contaminants were another major cause of disrupted herd subfertility. A variety of chemical contaminants with spermatoxic activities were identified, with their source being residual detergents and disinfectants, inferior semen extender (e.g., inclusion errors, impurities, inferior ingredients), reconstitution water quality, and plastic toxicity. Success in contaminant identification was best achieved through the combined use of objective pre-use data on the extended semen product along with post-use fecundity data from the breeding farm(s). Using a temporal overlayment and point of time determination, targeted in vitro diagnostics were employed, including spermiogram analyses, microbiological methodologies, and analytical chemistry. Investigation outcomes included establishing robust stud hygiene and sanitation procedures, implementation of scientifically-based quality assurance/quality control programs that use sperm-safe screening to validate quality and consistency of supplies prior to acceptance and use, and stud-specific input monitoring practices.
Topics: Swine; Male; Animals; Semen; Semen Preservation; Spermatozoa; Bacteria; Reproduction; Mammals
PubMed: 36191426
DOI: 10.1016/j.anireprosci.2022.107086 -
Current Biology : CB Jun 2017Seminal fluid does more than transport sperm. Hopkins et al., describe the diverse features and functions of seminal fluid, and its role in evolution and medicine.
Seminal fluid does more than transport sperm. Hopkins et al., describe the diverse features and functions of seminal fluid, and its role in evolution and medicine.
Topics: Animals; Biological Evolution; Humans; Male; Semen; Sexual Behavior, Animal; Species Specificity; Spermatozoa
PubMed: 28586660
DOI: 10.1016/j.cub.2017.03.063 -
Chemical Communications (Cambridge,... Jul 2018Amyloid fibrils are linear polypeptide aggregates with a cross-β structure. These fibrils are best known for their association with neurodegenerative diseases, such as... (Review)
Review
Amyloid fibrils are linear polypeptide aggregates with a cross-β structure. These fibrils are best known for their association with neurodegenerative diseases, such as Alzheimer's or Parkinson's, but they may also be used by living organisms as functional units, e.g. in the synthesis of melanin or in the formation of bacterial biofilms. About a decade ago, in a search for semen factors that modulate infection by HIV-1 (a sexually transmitted virus and the causative agent of the acquired immune deficiency syndrome (AIDS)), it was demonstrated that semen harbors amyloid fibrils capable of markedly increasing HIV infection rates. This discovery not only created novel opportunities to prevent sexual HIV-1 transmission but also stimulated research to unravel the natural role of these factors. We discuss here the identification of these intriguing structures, their molecular properties, and their effects on both sexually transmitted diseases and reproductive health. Moreover, we review strategies to antagonize semen amyloid to prevent sexual transmission of viruses.
Topics: Amyloidogenic Proteins; Animals; HIV Infections; HIV-1; Humans; Immunity, Innate; Male; Protein Aggregates; Protein Multimerization; Semen; Seminal Plasma Proteins
PubMed: 29873340
DOI: 10.1039/c8cc01491d -
Investigative and Clinical Urology Mar 2021As age increases, oxidative stress increases, sperm motility decreases, and DNA fragmentation increases. To date, reports of age-related effects on semen have focused on...
PURPOSE
As age increases, oxidative stress increases, sperm motility decreases, and DNA fragmentation increases. To date, reports of age-related effects on semen have focused on reactive oxygen species (ROS) or total antioxidant capacity (TAC) as indicators of oxidative stress. However, assessments of ROS and TAC must be considered within a more comprehensive context in order to correctly evaluate oxidative stress and interpret findings. In this regard, the purpose of this study was to investigate the relationship between the static oxidation reduction potential (sORP) and paternal age with the goal of using the sORP as an indicator of semen oxidative stress.
MATERIALS AND METHODS
Semen samples from 173 men were analyzed for the following parameters: volume, motility, and beat cross frequency (BCF). The sORP was measured by using the MiOXSYS™ system. The correlation between semen parameters and the sORP level was analyzed as a function of age. The rate of sORP positivity was compared between men <34 and ≥34 years of age, with a positive sORP defined as a level ≥1.38.
RESULTS
Volume, motility, and BCF were negatively correlated with age (p<0.001). The semen sORP level was positively correlated with age (p<0.05). The rate of sORP positivity was significantly increased in men ≥34 years of age compared with that in men <34 years of age (33% compared with 12%, respectively; p<0.01).
CONCLUSIONS
The sORP may play a role in age-related decreases in semen parameters (volume, motility, and BCF). The rate of sORP positivity increased significantly after 34 years of age.
Topics: Adult; Age Factors; Aging; Humans; Male; Middle Aged; Oxidative Stress; Semen; Young Adult
PubMed: 33660452
DOI: 10.4111/icu.20200066 -
Physiological Reviews Jul 2020Seminal fluid is often assumed to have just one function in mammalian reproduction, delivering sperm to fertilize oocytes. But seminal fluid also transmits signaling... (Review)
Review
Seminal fluid is often assumed to have just one function in mammalian reproduction, delivering sperm to fertilize oocytes. But seminal fluid also transmits signaling agents that interact with female reproductive tissues to facilitate conception and .pregnancy. Upon seminal fluid contact, female tissues initiate a controlled inflammatory response that affects several aspects of reproductive function to ultimately maximize the chances of a male producing healthy offspring. This effect is best characterized in mice, where the female response involves several steps. Initially, seminal fluid factors cause leukocytes to infiltrate the female reproductive tract, and to selectively target and eliminate excess sperm. Other signals stimulate ovulation, induce an altered transcriptional program in female tract tissues that modulates embryo developmental programming, and initiate immune adaptations to promote receptivity to implantation and placental development. A key result is expansion of the pool of regulatory T cells that assist implantation by suppressing inflammation, mediating tolerance to male transplantation antigens, and promoting uterine vascular adaptation and placental development. Principal signaling agents in seminal fluid include prostaglandins and transforming growth factor-β. The balance of male signals affects the nature of the female response, providing a mechanism of ‟cryptic female choiceˮ that influences female reproductive investment. Male-female seminal fluid signaling is evident in all mammalian species investigated including human, and effects of seminal fluid in invertebrates indicate evolutionarily conserved mechanisms. Understanding the female response to seminal fluid will shed new light on infertility and pregnancy disorders and is critical to defining how events at conception influence offspring health.
Topics: Animals; Female; Genitalia, Female; Inflammation; Male; Reproduction; Semen; Signal Transduction
PubMed: 31999507
DOI: 10.1152/physrev.00013.2018 -
PloS One 2019Egg yolk is a common ingredient of mammalian semen extender to protect sperm against initial cold shock. However, egg yolk has biosecurity risks. Our main objectives... (Comparative Study)
Comparative Study
Egg yolk is a common ingredient of mammalian semen extender to protect sperm against initial cold shock. However, egg yolk has biosecurity risks. Our main objectives were to cryopreserve bull semen without egg yolk using exogenous cholesterol and to study the protective role of glycerol in egg yolk-free semen extender. Other objectives were to compare protein profiles and in vitro fertilization potential of bull sperm frozen with and without egg yolk. In first experiment, semen was either diluted in conventional tris-egg yolk glycerol (TEYG control) extender or first treated with cholesterol-cyclodextrin complex (CC, 2 mg/ml semen) followed by dilution in egg yolk-free tris-glycerol (TG) extender (collectively called as "CC+TG") at 22°C or 4°C, and frozen. Post-thaw sperm motion characteristics were similar between CC+TG and TEYG control extenders, and temperature of glycerol addition. In second experiment, semen was frozen in CC+TG extender varying in glycerol concentration (7 to 0%; v/v). Post-thaw sperm quality decreased with the decline in glycerol concentration in TG extender, even higher concentration of CC complex (3 or 4 mg/ml semen) could not protect sperm in the absence of glycerol in TG extender. In third experiment, SDS electrophoresis of proteins from fresh sperm and sperm frozen in CC+TG, and TEYG control extenders was conducted. Protein profiles in fresh sperm and CC+TG frozen sperm were almost similar. Egg yolk proteins bound tightly with sperm plasma membrane. In fourth experiment, in vitro fertilization potentials of sperm frozen in TEYG control and CC+TG extenders were tested. Cleavage and blastocyst rates of semen frozen in CC+TG and TEYG control extenders were similar. In conclusion, cholesterol-cyclodextrin replaced egg yolk from the semen extender; glycerol remained essential for egg yolk-free sperm cryopreservation; and CC+TG extender did not modify sperm plasma membrane CC+TG whereas egg yolk extender changed the plasma membrane composition of bull sperm.
Topics: Animals; Cattle; Cell Differentiation; Cryopreservation; Cryoprotective Agents; Egg Yolk; Fertilization in Vitro; Glycerol; Male; Semen; Semen Preservation
PubMed: 31613900
DOI: 10.1371/journal.pone.0223977 -
Andrology Sep 2018Seminal cytokines were previously reported to adversely affect process of spermatogenesis and ultimately induce poor semen quality. However, association between both...
Seminal cytokines were previously reported to adversely affect process of spermatogenesis and ultimately induce poor semen quality. However, association between both IL-6 and TNF-α and leukocytospermia was not yet settled. The aim of this study was to evaluate the association between leukocytospermia and levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in semen of infertile men. This cross-sectional study included 100 age-matched (≥18-45 years.) men. Participants were divided into four groups with 25 patients in each group: Group (A) - infertile patients with leukocytospermia and normal other semen parameters; Group (B) - infertile patients with leukocytospermia and abnormal semen parameters; Group (C) - infertile patients with oligospermia and/or asthenospermia and/or teratospermia but with no leukocytospermia; Group (D) - fertile patients with normal semen parameters and without leukocytospermia. All patients were assessed by detailed medical, sexual, fertility history, and complete physical examination. Laboratory assessment included hormonal and semen analysis and assessment of IL-6 and TNF-α in semen plasma. There were significant differences among the study groups regarding total sperm count, sperm concentration, and progressive motility (p < 0.05 for each). There was significant increase in semen WBC counts in groups A and B vs. groups C and D (p = 0.003). There were significant associations between increase levels of WBCs ≥ 5/HPF and decrease levels of total sperm count (p = 0.023), sperm concentration (p = 0.001), and sperm progressive motility (p = 0.02). There were significant upregulations in mean level of IL-6 (p = 0.001) and mean level of TNF-α (p = 0.003) in groups A and B vs. groups C and D. Overall, leukocytospermia is associated with reduction in sperm count, progressive motility and further upregulation of seminal IL-6 and TNF-α. The effect of treatment of leukocytospermia on the level of seminal cytokines is important point of future research.
Topics: Adolescent; Adult; Cross-Sectional Studies; Humans; Infertility, Male; Interleukin-6; Leukocytes; Male; Middle Aged; Semen; Semen Analysis; Tumor Necrosis Factor-alpha; Young Adult
PubMed: 29981212
DOI: 10.1111/andr.12513