Showing papers on "Sperm published in 2018"

Sperm-Hybrid Micromotor for Targeted Drug Delivery

Abstract: A sperm-driven micromotor is presented as a targeted drug delivery system, which is appealing to potentially treat diseases in the female reproductive tract. This system is demonstrated to be an efficient drug delivery vehicle by first loading a motile sperm cell with an anticancer drug (doxorubicin hydrochloride), guiding it magnetically, to an in vitro cultured tumor spheroid, and finally freeing the sperm cell to deliver the drug locally. The sperm release mechanism is designed to liberate the sperm when the biohybrid micromotor hits the tumor walls, allowing it to swim into the tumor and deliver the drug through the sperm–cancer cell membrane fusion. In our experiments, the sperm cells exhibited a high drug encapsulation capability and drug carrying stability, conveniently minimizing toxic side effects and unwanted drug accumulation in healthy tissues. Overall, sperm cells are excellent candidates to operate in physiological environments, as they neither express pathogenic proteins nor proliferate to...

Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs.

Abstract: The discovery of RNAs (for example, messenger RNAs, non-coding RNAs) in sperm has opened the possibility that sperm may function by delivering additional paternal information aside from solely providing the DNA 1 . Increasing evidence now suggests that sperm small non-coding RNAs (sncRNAs) can mediate intergenerational transmission of paternally acquired phenotypes, including mental stress2,3 and metabolic disorders4-6. How sperm sncRNAs encode paternal information remains unclear, but the mechanism may involve RNA modifications. Here we show that deletion of a mouse tRNA methyltransferase, DNMT2, abolished sperm sncRNA-mediated transmission of high-fat-diet-induced metabolic disorders to offspring. Dnmt2 deletion prevented the elevation of RNA modifications (m5C, m2G) in sperm 30-40 nt RNA fractions that are induced by a high-fat diet. Also, Dnmt2 deletion altered the sperm small RNA expression profile, including levels of tRNA-derived small RNAs and rRNA-derived small RNAs, which might be essential in composing a sperm RNA 'coding signature' that is needed for paternal epigenetic memory. Finally, we show that Dnmt2-mediated m5C contributes to the secondary structure and biological properties of sncRNAs, implicating sperm RNA modifications as an additional layer of paternal hereditary information.

Sperm cryopreservation: A review on current molecular cryobiology and advanced approaches.

Abstract: The cryopreservation of spermatozoa was introduced in the 1960s as a route to fertility preservation. Despite the extensive progress that has been made in this field, the biological and biochemical mechanisms involved in cryopreservation have not been thoroughly elucidated to date. Various factors during the freezing process, including sudden temperature changes, ice formation and osmotic stress, have been proposed as reasons for poor sperm quality post-thaw. Little is known regarding the new aspects of sperm cryobiology, such as epigenetic and proteomic modulation of sperm and trans-generational effects of sperm freezing. This article reviews recent reports on molecular and cellular modifications of spermatozoa during cryopreservation in order to collate the existing understanding in this field. The aim is to discuss current freezing techniques and novel strategies that have been developed for sperm protection against cryo-damage, as well as evaluating the probable effects of sperm freezing on offspring health.

Paternal diet programs offspring health through sperm- and seminal plasma-specific pathways in mice

Abstract: The association between poor paternal diet, perturbed embryonic development, and adult offspring ill health represents a new focus for the Developmental Origins of Health and Disease hypothesis However, our understanding of the underlying mechanisms remains ill-defined We have developed a mouse paternal low-protein diet (LPD) model to determine its impact on semen quality, maternal uterine physiology, and adult offspring health We observed that sperm from LPD-fed male mice displayed global hypomethylation associated with reduced testicular expression of DNA methylation and folate-cycle regulators compared with normal protein diet (NPD) fed males Furthermore, females mated with LPD males display blunted preimplantation uterine immunological, cell signaling, and vascular remodeling responses compared to controls These data indicate paternal diet impacts on offspring health through both sperm genomic (epigenetic) and seminal plasma (maternal uterine environment) mechanisms Extending our model, we defined sperm- and seminal plasma-specific effects on offspring health by combining artificial insemination with vasectomized male mating of dietary-manipulated males All offspring derived from LPD sperm and/or seminal plasma became heavier with increased adiposity, glucose intolerance, perturbed hepatic gene expression symptomatic of nonalcoholic fatty liver disease, and altered gut bacterial profiles These data provide insight into programming mechanisms linking poor paternal diet with semen quality and offspring health

Cannabinoid exposure and altered DNA methylation in rat and human sperm.

Abstract: Little is known about the reproductive effects of paternal cannabis exposure. We evaluated associations between cannabis or tetrahydrocannabinol (THC) exposure and altered DNA methylation in sperm ...

Decline in sperm count in European men during the past 50 years.

Abstract: Purpose:To investigate whether the sperm concentration of European men is deteriorating over the past 50 years of time.Materials and Methods:We analysed the data published in English language artic...

Molecular Basis of Human Sperm Capacitation.

Abstract: In the early 1950s, Austin and Chang independently described the changes that are required for the sperm to fertilize oocytes in vivo. These changes were originally grouped under name of "capacitation" and were the first step in the development of in vitro fertilization (IVF) in humans. Following these initial and fundamental findings, a remarkable number of observations led to characterization of the molecular steps behind this process. The discovery of certain sperm-specific molecules and the possibility to record ion currents through patch-clamp approaches helped to integrate the initial biochemical observation with the activity of ion channels. This is of particular importance in the male gamete due to the fact that sperm are transcriptionally inactive. Therefore, sperm must control all these changes that occur during their transit through the male and female reproductive tracts by complex signaling cascades that include post-translational modifications. This review is focused on the principal molecular mechanisms that govern human sperm capacitation with particular emphasis on comparing all the reported pieces of evidence with the mouse model.

Zinc is an Essential Element for Male Fertility: A Review of Zn Roles in Men's Health, Germination, Sperm Quality, and Fertilization.

Abstract: Zinc (Zn) is the second most abundant trace element in human, which can't be stored in the body, thus regular dietary intake is required. This review explained the physiological and pathogenesis roles of zinc in men's health and its potentials in germination, quality of sperm, and fertilization. Our investigation showed that Zn contained many unique properties in human, especially males. The antioxidant quality is one of them. Also, the increased reactive oxygen species levels in the seminal plasma of men who are both infertile and smokers influence the Zn content of seminal plasma in a way that physiology of spermatozoa can be affected as well. Moreover, Zn acts as a toxic repercussionagainst heavy metals and cigarette inflammatory agents. Zinc as a hormone balancer helps hormones such as testosterone, prostate and sexual healthand functions as an antibacterial agent in men's urea system. It plays a role in epithelial integrity, showing that Zn is essential for maintaining the lining of the reproductive organs and may have a regulative role in the progress of capacitation and acrosome reaction. In contrast, Zn deficiency impedes spermatogenesis and is a reason for sperm abnormalities and has a negative effect on serum testosterone concentration. Based on these findings, Zn microelement is very essential for male fertility. It could be considered as a nutrient marker with many potentials in prevention, diagnosis, and treatment of male infertility.

Transcription factor DUO1 generated by neo-functionalization is associated with evolution of sperm differentiation in plants

Abstract: Evolutionary mechanisms underlying innovation of cell types have remained largely unclear. In multicellular eukaryotes, the evolutionary molecular origin of sperm differentiation is unknown in most lineages. Here, we report that in algal ancestors of land plants, changes in the DNA-binding domain of the ancestor of the MYB transcription factor DUO1 enabled the recognition of a new cis-regulatory element. This event led to the differentiation of motile sperm. After neo-functionalization, DUO1 acquired sperm lineage-specific expression in the common ancestor of land plants. Subsequently the downstream network of DUO1 was rewired leading to sperm with distinct morphologies. Conjugating green algae, a sister group of land plants, accumulated mutations in the DNA-binding domain of DUO1 and lost sperm differentiation. Our findings suggest that the emergence of DUO1 was the defining event in the evolution of sperm differentiation and the varied modes of sexual reproduction in the land plant lineage.

The contribution of human sperm proteins to the development and epigenome of the preimplantation embryo.

Abstract: Background Knowledge of the proteomic composition of the gametes is essential to understand reproductive functions. Most of the sperm proteins are related to spermatogenesis and sperm function, but less abundant protein groups with potential post-fertilization roles have also been detected. The current data are challenging our understanding of sperm biology and functionality, demanding an integrated analysis of the proteomic and RNA-seq datasets available for spermatozoa, oocytes and early embryos, in order to unravel the impact of the male gamete on the generation of the new individual. Objective and rationale The aim of this review is to compile human sperm proteins and to identify and infer their origin and discuss their relevance during oocyte fecundation, preimplantation embryogenesis and epigenetic inheritance. Search methods The scientific literature was comprehensively searched for proteomic studies on human sperm, oocytes, embryos, and additional reproductive cells and fluids. Proteins were compiled and functionally classified according to Gene Ontology annotations and the mouse phenotypes integrated into the Mouse Genome Informatics database. High-throughput RNA datasets were used to decipher the origin of embryo proteins. The tissue origin of sperm proteins was inferred on the basis of RNA-seq and protein data available in the Human Protein Atlas database. Outcomes So far, 6871 proteins have been identified and reported in sperm, 1376 in the oocyte and 1300 in blastocyst. With a deeper analysis of the sperm proteome, 103 proteins with known roles in the processes of fertilization and 93 with roles in early embryo development have been identified. Additionally, 560 sperm proteins have been found to be involved in modulating gene expression by regulation of transcription, DNA methylation, histone post-translational modifications and non-coding RNA biogenesis. Some of these proteins may be critical for gene expression regulation after embryo genome activation, and therefore, may be potentially involved in epigenetic transmission of altered phenotypes. Furthermore, the integrative analysis of the sperm, oocyte and blastocyst proteomes and transcriptomes revealed a set of embryo proteins with an exclusive paternal origin, some of which are crucial for correct embryogenesis and, possibly, for modulation of the offspring phenotype. The analysis of the expression of sperm proteins, at both RNA and protein levels, in tissues not only from the male reproductive tract but also from peripheral organs, has suggested a putative extra-testicular origin for some sperm proteins. These proteins could be imported into sperm from the accessory sex glands and other tissues, most likely through exosomes. Wider implications These integrative proteome and transcriptome analyses focused on specific groups of proteins, rather than on enriched pathways, identified important sperm proteins which may be involved in early embryogenesis and provided evidence which could support the hypothesis of paternal epigenetic inheritance. The putative extra-testicular origin of some sperm proteins suggests not only the involvement of accessory sex glands in fertilization and epigenetic information transmission, but also that some proteins from additional organs could possibly contribute information to the offspring phenotype. These findings should stimulate further research in the field.

Reduced levels of miRNAs 449 and 34 in sperm of mice and men exposed to early life stress

Abstract: Exposure of male mice to early life stress alters the levels of specific sperm miRNAs that promote stress-associated behaviors in their offspring. To begin to evaluate whether similar phenomena occur in men, we searched for sperm miRNA changes that occur in both mice and men exposed to early life stressors that have long-lasting effects. For men, we used the Adverse Childhood Experience (ACE) questionnaire. It reveals the degree of abusive and/or dysfunctional family experiences when young, which increases risks of developing future psychological and physical disorders. For male mice, we used adolescent chronic social instability (CSI) stress, which not only enhances sociability defects for >1 year, but also anxiety and defective sociability in female offspring for multiple generations through the male lineage. Here we found a statistically significant inverse correlation between levels of multiple miRNAs of the miR-449/34 family and ACE scores of Caucasian males. Remarkably, we found members of the same sperm miRNA family are also reduced in mice exposed to CSI stress. Thus, future studies should be designed to directly test whether reduced levels of these miRNAs could be used as unbiased indicators of current and/or early life exposure to severe stress. Moreover, after mating stressed male mice, these sperm miRNA reductions persist in both early embryos through at least the morula stage and in sperm of males derived from them, suggesting these miRNA changes contribute to transmission of stress phenotypes across generations. Since offspring of men exposed to early life trauma have elevated risks for psychological disorders, these findings raise the possibility that a portion of this risk may be derived from epigenetic regulation of these sperm miRNAs.

Absence of CFAP69 Causes Male Infertility due to Multiple Morphological Abnormalities of the Flagella in Human and Mouse.

Abstract: The multiple morphological abnormalities of the flagella (MMAF) phenotype is among the most severe forms of sperm defects responsible for male infertility. The phenotype is characterized by the presence in the ejaculate of immotile spermatozoa with severe flagellar abnormalities including flagella being short, coiled, absent, and of irregular caliber. Recent studies have demonstrated that MMAF is genetically heterogeneous, and genes thus far associated with MMAF account for only one-third of cases. Here we report the identification of homozygous truncating mutations (one stop-gain and one splicing variant) in CFAP69 of two unrelated individuals by whole-exome sequencing of a cohort of 78 infertile men with MMAF. CFAP69 encodes an evolutionarily conserved protein found at high levels in the testis. Immunostaining experiments in sperm from fertile control individuals showed that CFAP69 localized to the midpiece of the flagellum, and the absence of CFAP69 was confirmed in both individuals carrying CFPA69 mutations. Additionally, we found that sperm from a Cfap69 knockout mouse model recapitulated the MMAF phenotype. Ultrastructural analysis of testicular sperm from the knockout mice showed severe disruption of flagellum structure, but histological analysis of testes from these mice revealed the presence of all stages of the seminiferous epithelium, indicating that the overall progression of spermatogenesis is preserved and that the sperm defects likely arise during spermiogenesis. Together, our data indicate that CFAP69 is necessary for flagellum assembly/stability and that in both humans and mice, biallelic truncating mutations in CFAP69 cause autosomal-recessive MMAF and primary male infertility.

Microfluidic sorting selects sperm for clinical use with reduced DNA damage compared to density gradient centrifugation with swim-up in split semen samples

Abstract: STUDY QUESTION Does microfluidic sorting improve the selection of sperm with lower DNA fragmentation over standard density-gradient centrifugation? SUMMARY ANSWER Microfluidic sorting of unprocessed semen allows for the selection of clinically usable, highly motile sperm with nearly undetectable levels of DNA fragmentation. WHAT IS KNOWN ALREADY Microfluidic devices have been explored to sort motile and morphologically normal sperm from a raw sample without centrifugation; however, it is uncertain whether DNA damage is reduced in this process. STUDY DESIGN, SIZE, DURATION This is a blinded, controlled laboratory study of differences in standard semen analysis parameters and the DNA fragmentation index (DFI) in split samples from infertile men (n = 70) that were discarded after routine semen analysis at an academic medical center. PARTICIPANTS/MATERIALS, SETTING, METHODS Sperm concentration, progressive motility and forward progression were assessed by microscopic examination. For each sample, the unprocessed semen was tested for DNA fragmentation and split for processing by density-gradient centrifugation with swim-up or sorting by a microfluidic chip. DNA fragmentation was assessed in unprocessed and processed samples by sperm chromatin dispersion assay. The DFI was calculated, from up to 300 cells per slide, as the number of cells with fragmented DNA divided by the number of cells counted per slide. MAIN RESULTS AND THE ROLE OF CHANCE The median DFI in unprocessed samples was 21% (interquartile range (IQR): 14-30). In paired analyses of all samples, those processed by the microfluidic chip demonstrated significantly decreased DFI compared to those processed by density-gradient centrifugation (P = 0.0029) and unprocessed samples (P < 0.0001). The median DFI for chip specimens was 0% (IQR: 0-2.4) while those processed by density-gradient centrifugation had a median DFI of 6% (IQR: 2-11). Unprocessed samples in the highest DFI quartile (DFI range: 31-40%) had a median DFI of 15% (IQR: 11-19%) after density-gradient centrifugation and DFI of 0% (IQR: 0-1.9%) after processing with the microfluidic chip (P = 0.02). LIMITATIONS, REASONS FOR CAUTION While a high DFI has been associated with poor outcomes with IVF/ICSI, there are limited data illustrating improvements in clinical outcomes with a reduction in DFI. As this study utilized discarded, non-clinical samples, clinical outcomes data are not available. WIDER IMPLICATIONS OF THE FINDINGS While microfluidic sorting of unprocessed semen allowed for the selection of clinically usable, highly motile sperm with nearly undetectable levels of DNA fragmentation, standard processing by density-gradient centrifugation with swim-up did not increase DNA fragmentation in an infertile population. The proposed microfluidic technology offers a flow-free approach to sort sperm, requiring no peripheral equipment or filtration step, while minimizing hands-on time. STUDY FUNDING/COMPETING INTEREST(S) No external funding to declare. Utkan Demirci, PhD is the Co-founder and Scientific Advisor for DxNow Inc., LevitasBio Inc. and Koek Biotech. Mitchell Rosen, MD is a member of the Clinical Advisory Board for DxNow Inc.

Rapid genome shrinkage in a self-fertile nematode reveals sperm competition proteins

Abstract: To reveal impacts of sexual mode on genome content, we compared chromosome-scale assemblies of the outcrossing nematode Caenorhabditis nigoni to its self-fertile sibling species, C. briggsae . C. nigoni ’s genome resembles that of outcrossing relatives but encodes 31% more protein-coding genes than C. briggsae . C. nigoni genes lacking C. briggsae orthologs were disproportionately small and male-biased in expression. These include the male secreted short ( mss ) gene family, which encodes sperm surface glycoproteins conserved only in outcrossing species. Sperm from mss -null males of outcrossing C. remanei failed to compete with wild-type sperm, despite normal fertility in noncompetitive mating. Restoring mss to C. briggsae males was sufficient to enhance sperm competitiveness. Thus, sex has a pervasive influence on genome content that can be used to identify sperm competition factors.

The enigmatic seminal plasma: a proteomics insight from ejaculation to fertilization.

Abstract: The ‘omics’ approach for a noninvasive diagnosis of male reproductive system disorders has gained momentum during the last decade, particularly from a screening and prognosis point of view. Due to the rapid development in assisted reproductive technologies (ART) over the years, the major focus of proteomic studies has been around the ejaculated spermatozoa. Although seminal plasma is not a requirement for ART, the question arose whether the role of seminal plasma is merely to transport spermatozoa. Seminal plasma (SP) contains a large diversity of proteins that are essential not only for sperm transport, but also for sperm protection and maturation. Most of the proteins bind to sperm surface through exosomes (epididymosomes and prostasomes), modulating sperm function, interaction with the female reproductive tract and finally fertilization. This review focuses on the state-of-art discoveries regarding SP proteome and its role in fertilization. Tissue-specific proteins in the SP have emerged as fundamental contributors for protein biomarker discovery. This is important for a noninvasive diagnosis of male infertility and development of new therapeutic approaches. Moreover, ART success rates may be improved by taking into account the critical role of seminal proteome in fertilization.

Diabetes Mellitus and Infertility: Different Pathophysiological Effects in Type 1 and Type 2 on Sperm Function.

Abstract: Although the prevalence of sub-infertility in diabetic patients in childbearing age is known, the mechanisms by which diabetes mellitus (DM) causes male infertility are not completely explained. This detrimental effect is achieved with a variety of mechanisms that include pre-testicular, testicular, and post-testicular pathogenetic moments and can be different in type 1 diabetes mellitus (DM1) and type 2 diabetes mellitus (DM2) patients because of type of diabetes, duration of disease, and glycemic metabolic compensation. Aim of this study was to evaluate whether diabetic disease can be considered a risk factor for infertility considering the etiopathogenetic differences between DM1 and DM2 on sperm function. We enrolled 38 DM1 patients and 55 DM2 patients with idiopathic infertility history >12 months, and 100 healthy fertile subjects. The following outcomes were evaluated in optical microscopy and flow cytometry: sperm function (by conventional and biofunctional sperm parameters) and signs of urogenital infection/inflammation (by sperm leukocyte concentrations and indices of oxidative stress). Moreover, an andrological evaluation (by didymo-epididymal ultrasound evaluation, serum total testosterone, LH, and FSH measurements) was performed in DM1 and DM2 patients compared to controls. Diabetic patients showed a higher risk of becoming infertile and the pathophysiological mechanisms of damage were different in DM1 and DM2. Conventional sperm parameters of diabetic patients are worse than controls (p < 0.05). The DM2 caused an inflammatory condition with increased oxidative stress resulting in decreased sperm vitality and increased sperm DNA fragmentation. DM1 altered epididymal voiding causing low ejaculate volume and mitochondrial damage resulting in decreased sperm motility. These findings and evidences support the contention that DM could be regarded as cause of male infertility suggesting that the prevention of diabetic disease in DM2 and the follow-up of seminal parameters in DM1 could prevent fertility decline in these categories of patients.

Sperm form and function: what do we know about the role of sexual selection?

Abstract: Sperm morphological variation has attracted considerable interest and generated a wealth of predominantly descriptive studies over the past three centuries. Yet, apart from biophysical studies linking sperm morphology to swimming velocity, surprisingly little is known about the adaptive significance of sperm form and the selective processes underlying its tremendous diversification throughout the animal kingdom. Here, we first discuss the challenges of examining sperm morphology in an evolutionary context and why our understanding of it is far from complete. Then, we review empirical evidence for how sexual selection theory applies to the evolution of sperm form and function, including putative secondary sexual traits borne by sperm.

Paternal factors contributing to embryo quality

Abstract: Advancing maternal and paternal age leads to a decrease in fertility, and hence, many infertile couples opt for assisted reproductive technologies [ART] to achieve biological parenthood. One of the key determinants of achieving a live outcome of ART, embryo quality, depends on both the quality of the oocyte and sperm that have created the embryo. Several studies have explored the effect of oocyte parameters on embryo quality, but the effects of sperm quality on the embryo have not been comprehensively evaluated. In this review, we assess the effect of various genetic factors of paternal origin on the quality and development of the embryo. The effects of sperm aneuploidy, sperm chromatin structure, deoxyribonucleic acid [DNA] fragmentation, role of protamines and histones, sperm epigenetic profile, and Y chromosome microdeletions were explored and found to negatively affect embryo quality. We propose that careful assessment of spermatozoal parameters is essential to achieve embryo development and a healthy live birth. However, the heterogeneity in test results and the different approaches of assessing a single sperm parameter highlight the need for more research and the development of standardized protocols to assess the role of sperm factors affecting embryo quality.

Sperm-borne phospholipase C zeta-1 ensures monospermic fertilization in mice.

Abstract: Sperm entry in mammalian oocytes triggers intracellular Ca2+ oscillations that initiate resumption of the meiotic cell cycle and subsequent activations. Here, we show that phospholipase C zeta 1 (PLCζ1) is the long-sought sperm-borne oocyte activation factor (SOAF). Plcz1 gene knockout (KO) mouse spermatozoa fail to induce Ca2+ changes in intracytoplasmic sperm injection (ICSI). In contrast to ICSI, Plcz1 KO spermatozoa induced atypical patterns of Ca2+ changes in normal fertilizations, and most of the fertilized oocytes ceased development at the 1–2-cell stage because of oocyte activation failure or polyspermy. We further discovered that both zona pellucida block to polyspermy (ZPBP) and plasma membrane block to polyspermy (PMBP) were delayed in oocytes fertilized with Plcz1 KO spermatozoa. With the observation that polyspermy is rare in astacin-like metalloendopeptidase (Astl) KO female oocytes that lack ZPBP, we conclude that PMPB plays more critical role than ZPBP in vivo. Finally, we obtained healthy pups from male mice carrying human infertile PLCZ1 mutation by single sperm ICSI supplemented with Plcz1 mRNA injection. These results suggest that mammalian spermatozoa have a primitive oocyte activation mechanism and that PLCζ1 is a SOAF that ensures oocyte activation steps for monospermic fertilization in mammals.

Review: Spermatogenesis in the bull

Abstract: Spermatogenesis is a finely regulated process of germ cell multiplication and differentiation leading to the production of spermatozoa in the seminiferous tubules. Spermatogenesis can be divided into three parts: spermatocytogenesis, meiosis and spermiogenesis. During spermatocytogenesis, germ cells engage in a cycle of several mitotic divisions that increases the yield of spermatogenesis and to renew stem cells and produce spermatogonia and primary spermatocytes. Meiosis involves duplication and exchange of genetic material and two cell divisions that reduce the chromosome number and yield four haploid round spermatids. Spermiogenesis involves the differentiation of round spermatids into fully mature spermatozoa released into the lumin of seminiferous tubules. The seminiferous epithelium is composed of several generations of germ cells due to the fact that new generations of sperm cells engage in the spermatogenic process without waiting for the preceding generations to have completed their evolution and to have disappeared as spermatozoa into the lumen of the tubules. In bulls, the duration of the seminiferous epithelium cycle is 13.5 days. The total duration of spermatogenesis is 61 days, that is 4.5 times the duration of the cycle of the seminiferous epithelium. The spermatogenetic wave is used to describe the spatial arrangement of cell associations along the tubules. Several theories have been described to explain the renewal of spermatogonia. Depending on the model, there are five or six spermatogonial mitoses explaining the renewal of stem cells and the proliferation of spermatogonia. Daily sperm production and germ cell degeneration can be quantified from numbers of germ cells in various steps of development throughout spermatogenesis. Bulls have a lower efficiency of spermatogenesis than most species examined, but higher than that of humans.

Effect of metabolic and antioxidant supplementation on sperm parameters in oligo-astheno-teratozoospermia, with and without varicocele: A double-blind placebo-controlled study.

Abstract: Since sperm require high energy levels to perform their specialised function, it is vital that essential nutrients are available for spermatozoa when they develop, capacitate and acquire motility. However, they are vulnerable to a lack of energy and excess amounts of reactive oxygen species, which can impair sperm function, lead to immotility, acrosomal reaction impairment, DNA fragmentation and cell death. This monocentric, randomised, double-blind, placebo-controlled trial investigated the effect of 6 months of supplementation with l-carnitine, acetyl-l-carnitine and other micronutrients on sperm quality in 104 subjects with oligo- and/or astheno- and/or teratozoospermia with or without varicocele. In 94 patients who completed the study, sperm concentration was significantly increased in supplemented patients compared to the placebo (p = .0186). Total sperm count also increased significantly (p = .0117) in the supplemented group as compared to the placebo group. Both, progressive and total motility were higher in supplemented patients (p = .0088 and p = .0120, respectively). Although pregnancy rate was not an endpoint of the study, of the 12 pregnancies that occurred during the follow-up, 10 were reported in the supplementation group. In general, all these changes were more evident in varicocele patients. In conclusion, supplementation with metabolic and antioxidant compounds could be efficacious when included in strategies to improve fertility.

Zinc ion flux during mammalian sperm capacitation.

Abstract: Sperm capacitation, the ultimate maturation event preparing mammalian spermatozoa for fertilization, was first described in 1951, yet its regulatory mechanisms remain poorly understood. The capacitation process encompasses an influx of bicarbonate and calcium ions, removal of decapacitating factors, changes of pH and sperm proteasomal activities, and the increased protein tyrosine phosphorylation. Here, we document a novel biological phenomenon of a unique zinc (Zn2+) ion redistribution associated with mammalian sperm in vitro capacitation (IVC). Using image-based flow cytometry (IBFC), we identified four distinct types of sperm zinc ion distribution patterns (further zinc signature) and their changes during IVC. The zinc signature was altered after sperm capacitation, reduced by proteasomal inhibitors, removed by zinc chelators, and maintained with addition of external ZnCl2. These findings represent a fundamental shift in the understanding of mammalian fertilization, paving the way for improved semen analysis, in vitro fertilization (IVF), and artificial insemination (AI).

Sperm acrosome reaction: its site and role in fertilization

Abstract: Manner and roles of sperm acrosome reaction in a variety of animals were compared.Summary Sentence

Heavy Chronic Intermittent Ethanol Exposure Alters Small Noncoding RNAs in Mouse Sperm and Epididymosomes.

Abstract: While the risks of maternal alcohol abuse during pregnancy are well-established, several preclinical studies suggest that chronic preconception alcohol consumption by either parent may also have significance consequences for offspring health and development. Notably, since isogenic male mice used in these studies are not involved in gestation or rearing of offspring, the cross-generational effects of paternal alcohol exposure suggest a germline-based epigenetic mechanism. Many recent studies have demonstrated that the effects of paternal environmental exposures such as stress or malnutrition can be transmitted to the next generation via alterations to small noncoding RNAs in sperm. Therefore, we used high throughput sequencing to examine the effect of preconception ethanol on small noncoding RNAs in sperm. We found that chronic intermittent ethanol exposure altered several small noncoding RNAs from three of the major small RNA classes in sperm, tRNA-derived small RNA (tDR), mitochondrial small RNA, and microRNA. Six of the ethanol-responsive small noncoding RNAs were evaluated with RT-qPCR on a separate cohort of mice and five of the six were confirmed to be altered by chronic ethanol exposure, supporting the validity of the sequencing results. In addition to altered sperm RNA abundance, chronic ethanol exposure affected post-transcriptional modifications to sperm small noncoding RNAs, increasing two nucleoside modifications previously identified in mitochondrial tRNA. Furthermore, we found that chronic ethanol reduced epididymal expression of a tRNA methyltransferase, Nsun2, known to directly regulate tDR biogenesis. Finally, ethanol-responsive sperm tDR are similarly altered in extracellular vesicles of the epididymis (i.e., epididymosomes), supporting the hypothesis that alterations to sperm tDR emerge in the epididymis and that epididymosomes are the primary source of small noncoding RNAs in sperm. These results add chronic ethanol to the growing list of paternal exposures that can affect small noncoding RNA abundance and nucleoside modifications in sperm. As small noncoding RNAs in sperm have been shown to causally induce heritable phenotypes in offspring, additional research is warranted to understand the potential effects of ethanol-responsive sperm small noncoding RNAs on offspring health and development.