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Showing papers on "Sperm published in 2021"


Journal ArticleDOI
TL;DR: The results indicate that the abnormal sperm quality in ICR mice caused by PS-MPS exposure is closely related to the Nrf2/HO-1/NF-κB pathway.

144 citations


Journal ArticleDOI
20 Jul 2021-JAMA
TL;DR: In this paper, the authors assessed sperm parameters before and after mRNA vaccine administration to address vaccine hesitancy based on concerns about fertility, and they found that MMR vaccine attenuated fertility.
Abstract: To address vaccine hesitancy based on concerns about fertility, this study assesses sperm parameters before and after mRNA vaccine administration.

102 citations


Journal ArticleDOI
TL;DR: This work will categorize the identified MMAF genes following the protein complexes, functions or biological processes they may be associated with, based on the current knowledge in the field.
Abstract: Spermatozoa contain highly specialized structural features reflecting unique functions required for fertilization. Among them, the flagellum is a sperm-specific organelle required to generate the motility, which is essential to reach the egg. The flagellum integrity is, therefore, critical for normal sperm function and flagellum defects consistently lead to male infertility due to reduced or absent sperm motility defined as asthenozoospermia. Multiple morphological abnormalities of the flagella (MMAF), also called short tails, is among the most severe forms of sperm flagellum defects responsible for male infertility and is characterized by the presence in the ejaculate of spermatozoa being short, coiled, absent and of irregular caliber. Recent studies have demonstrated that MMAF is genetically heterogeneous which is consistent with the large number of proteins (over one thousand) localized in the human sperm flagella. In the past 5 years, genomic investigation of the MMAF phenotype allowed the identification of 18 genes whose mutations induce MMAF and infertility. Here we will review information about those genes including their expression pattern, the features of the encoded proteins together with their localization within the different flagellar protein complexes (axonemal or peri-axonemal) and their potential functions. We will categorize the identified MMAF genes following the protein complexes, functions or biological processes they may be associated with, based on the current knowledge in the field.

94 citations


Journal ArticleDOI
TL;DR: In this paper, the connection between changes in multiple seminal biomarkers and reproductive function in male patients recovering from COVID-19 infection was addressed, and the direct experimental evidence that the male reproductive system could be targeted and damaged by the infection was provided.
Abstract: The existing evidence suggests that the human reproductive system may be potentially vulnerable to COVID-19 infection. However, little is known about the virus-host interaction of COVID-19 in sperm cells. We are the first to address the connection between changes in multiple seminal biomarkers and reproductive function in male patients recovering from COVID-19. In a prospective longitudinal cohort study, seminal ACE2 activity, markers of inflammation and oxidative stress, apoptotic variables, and semen quality parameters were evaluated at 10-day intervals for a maximum follow-up time of 60 days among male patients with laboratory-confirmed COVID-19 (n = 84) and healthy controls (CON; n = 105). At the baseline and the subsequent follow-ups, the COVID-19 group revealed significantly higher levels of seminal plasma ACE2 enzymatic activity, IL-1β, IL-6, IL-8, IL-10, TGF-β, TNF-α, IFN-α, IFN-γ, ROS, caspase-8, caspase-9, and caspase-3 activity as well as lower levels of SOD activity than those in the CON group (P < 0.05). These perturbations tended to persist over time and were correlated with significant impairments in semen volume, progressive motility, sperm morphology, sperm concentration, and the number of spermatozoa. We provide the direct experimental evidence that the male reproductive system could be targeted and damaged by the COVID-19 infection. These findings go beyond our current understanding of the disease, suggesting that the reproductive function of the patients recovering from the disease should be precisely followed and evaluated to detect and avoid more serious reproductive problems in the future, as they may develop a transient state of male subfertility like those with oligoasthenoteratozoospermia.

68 citations


Journal ArticleDOI
TL;DR: The use of next‐generation sequencing techniques has provided a better understanding of the human microbiome, and dysbiosis has been reported to impact health.
Abstract: BACKGROUND Male factor is attributable in up to 50% of cases of infertility. In vitro studies demonstrate that bacteria can negatively impact sperm function. The use of next-generation sequencing techniques has provided a better understanding of the human microbiome, and dysbiosis has been reported to impact health. Evidence regarding the impact of the semen microbiome on sperm function and fertility remains conflicting. MATERIALS AND METHODS A systematic search was conducted in accordance with the Preferred Reporting Items for Reviews and Meta-analysis (PRISMA) statement. The databases MEDLINE, OVID and PubMed were searched to identify English language studies related to the identification of bacteria in the semen of infertile and fertile men, between 1992 and 2019. Fifty-five observational studies were included, with 51 299 subjects. We included studies identifying bacteria using next-generation sequencing, culture or polymerase chain reaction. RESULTS The semen microbiome was rich and diverse in both fertile and infertile men. Three NGS studies reported clustering of the seminal microbiome with a predominant species. Lactobacillus and Prevotella were dominant in respective clusters. Lactobacillus was associated with improvements in semen parameters. Prevotella appeared to exert a negative effect on sperm quality. Bacteriospermia negatively impacted sperm concentration and progressive motility, and DNA fragmentation index (DFI; MD: 3.518, 95% CI: 0.907 to 6.129, P = .008). There was an increased prevalence of ureaplasma urealyticum in infertile men (OR: 2.25, 95% CI: 1.47-3.46). Ureaplasma urealyticum negatively impacted concentration and morphology. There was no difference in the prevalence of chlamydia trachomatis between fertile and infertile men and no significant impact on semen parameters. Enterococcus faecalis negatively impacted total motility, and Mycoplasma hominis negatively impacted concentration, PM and morphology. DISCUSSION AND CONCLUSIONS Ureaplasma urealyticum, Enterococcus faecalis, Mycoplasma hominis and Prevotella negatively impact semen parameters, whereas Lactobacillus appears to protect sperm quality. These findings may facilitate the development of novel therapies (eg probiotics), although the evidence regarding the impact of the seminal microbiome on fertility is inconclusive and further studies are needed to investigate this association.

63 citations


Journal ArticleDOI
TL;DR: In this paper, a review aimed to summarize the roles of mitochondria in male fertility depending on the sperm developmental stage (from male reproductive tract to female reproductive tract) and established the new signaling pathway using previous proteomic data associated with male fertility.
Abstract: Mitochondria are structurally and functionally distinct organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS), to provide energy to spermatozoa. They can also produce reactive oxidation species (ROS). While a moderate concentration of ROS is critical for tyrosine phosphorylation in cholesterol efflux, sperm-egg interaction, and fertilization, excessive ROS generation is associated with male infertility. Moreover, mitochondria participate in diverse processes ranging from spermatogenesis to fertilization to regulate male fertility. This review aimed to summarize the roles of mitochondria in male fertility depending on the sperm developmental stage (from male reproductive tract to female reproductive tract). Moreover, mitochondria are also involved in testosterone production, regulation of proton secretion into the lumen to maintain an acidic condition in the epididymis, and sperm DNA condensation during epididymal maturation. We also established the new signaling pathway using previous proteomic data associated with male fertility, to understand the overall role of mitochondria in male fertility. The pathway revealed that male infertility is associated with a loss of mitochondrial proteins in spermatozoa, which induces low sperm motility, reduces OXPHOS activity, and results in male infertility.

62 citations


Journal ArticleDOI
TL;DR: Improved understanding of spermatozoan ion channels and transporters will help elucidate the delicate and dynamic regulation of Ca 2+ homeostasis in sperm motility and fertility.
Abstract: Mammalian sperm cells must respond to cues originating from along the female reproductive tract and from the layers of the egg in order to complete their fertilization journey. Dynamic regulation of ion signalling is, therefore, essential for sperm cells to adapt to their constantly changing environment. Over the past 15 years, direct electrophysiological recordings together with genetically modified mouse models and human genetics have confirmed the importance of ion channels, including the principal Ca2+-selective plasma membrane ion channel CatSper, for sperm activity. Sperm ion channels and membrane receptors are attractive targets for both the development of contraceptives and infertility treatment drugs. Furthermore, in this era of assisted reproductive technologies, understanding the signalling processes implicated in defective sperm function, particularly those arising from genetic abnormalities, is of the utmost importance not only for the development of infertility treatments but also to assess the overall health of a patient and his children. Future studies to improve reproductive health care and overall health care as a function of the ability to reproduce should include identification and analyses of gene variants that underlie human infertility and research into fertility-related molecules. Mammalian sperm must respond to a variety of cues, and dynamic regulation of ion signalling is, therefore, essential for sperm cells to adapt to their environment. In this Review, the authors describe the ion channels and membrane receptors controlling sperm activity, in particular the principal Ca2+-selective plasma membrane ion channel CatSper, and consider how sperm ion channels and membrane receptors are attractive targets for therapeutics and how these signalling processes might have implications for assisted reproductive technologies.

60 citations


Journal ArticleDOI
TL;DR: The results suggest that maintaining a healthy body weight is important for increasing sperm quality parameters and potentially male fertility.
Abstract: The present updated systematic review and meta-analysis aims to summarize the evidence from published studies with low risk for any important bias (based on methodological quality assessment) investigating the potential associations of adiposity with sperm quality and reproductive hormones. We conducted a systematic search of the literature published in MEDLINE-PubMed and EMBASE through June 2019. Based on the criteria in our review, 169 eligible publications were used for data abstraction. Finally, 60 articles were included in the qualitative analysis and 28 in the quantitative analysis. Our systematic review results indicated that overweight and/or obesity were associated with low semen quality parameters (i.e., semen volume, sperm count and concentration, sperm vitality and normal morphology) and some specific reproductive hormones (e.g., inhibin B, total testosterone and sex hormone-binding globulin). Overweight and/or obesity were also positively associated with high estradiol concentrations. Meta-analysis indicated that overweight and/or obesity categories were associated with lower sperm quality (i.e., semen volume, sperm count and concentration, sperm vitality, total motility and normal morphology), and underweight category was likewise associated with low sperm normal morphology. In conclusion, our results suggest that maintaining a healthy body weight is important for increasing sperm quality parameters and potentially male fertility.

50 citations


Journal ArticleDOI
TL;DR: In this paper, the impact of reactive oxygen species (ROS) at multiple levels in sperm: the genome, proteome, lipidome, epigenome, and epigenome was discussed.
Abstract: Besides ATP production, mitochondria are key organelles in several cellular functions, such as steroid hormone biosynthesis, calcium homoeostasis, intrinsic apoptotic pathway, and the generation of reactive oxygen species (ROS). Despite the loss of the majority of the cytoplasm occurring during spermiogenesis, mammalian sperm preserves a number of mitochondria that rearrange in a tubular structure at the level of the sperm flagellum midpiece. Although sperm mitochondria are destroyed inside the zygote, the integrity and the functionality of these organelles seem to be critical for fertilization and embryo development. The aim of this review was to discuss the impact of mitochondria-produced ROS at multiple levels in sperm: the genome, proteome, lipidome, epigenome. How diet, aging and environmental pollution may affect sperm quality and offspring health-by exacerbating oxidative stress-will be also described.

47 citations


Journal ArticleDOI
TL;DR: Greater understanding of sperm mitochondrial function and its correlation with sperm quality could provide further insights into their contribution in the assessment of the infertile male.
Abstract: Mitochondria have multiple functions, including synthesis of adenine triphosphate, production of reactive oxygen species, calcium signalling, thermogenesis and apoptosis. Mitochondria have a significant contribution in regulating the various physiological aspects of reproductive function, from spermatogenesis up to fertilisation. Mitochondrial functionality and intact mitochondrial membrane potential are a pre-requisite for sperm motility, hyperactivation, capacitation, acrosin activity, acrosome reaction and DNA integrity. Optimal mitochondrial activity is therefore crucial for human sperm function and semen quality. However, the precise role of mitochondria in spermatozoa remains to be fully explored. Defects in sperm mitochondrial function severely impair the maintenance of energy production required for sperm motility and may be an underlying cause of asthenozoospermia. Sperm mtDNA is susceptible to oxidative damage and mutations that could compromise sperm function leading to infertility. Males with abnormal semen parameters have increased mtDNA copy number and reduced mtDNA integrity. This review discusses the role of mitochondria in sperm function, along with the causes and impact of its dysfunction on male fertility. Greater understanding of sperm mitochondrial function and its correlation with sperm quality could provide further insights into their contribution in the assessment of the infertile male.

46 citations


Journal ArticleDOI
TL;DR: In this paper, the consequences of COVID-19 on sperm parameters after recovery were investigated, and the results indicated an adverse but potentially reversible consequence of the coronavirus disease on sperm quality.
Abstract: The novel coronavirus disease (COVID-19) pandemic is emerging as a global health threat and shows a higher risk for men than women. Thus far, the studies on andrological consequences of COVID-19 are limited. To ascertain the consequences of COVID-19 on sperm parameters after recovery, we recruited 41 reproductive-aged male patients who had recovered from COVID-19, and analyzed their semen parameters and serum sex hormones at a median time of 56 days after hospital discharge. For longitudinal analysis, a second sampling was obtained from 22 of the 41 patients after a median time interval of 29 days from first sampling. Compared with controls who had not suffered from COVID-19, the total sperm count, sperm concentration, and percentages of motile and progressively motile spermatozoa in the patients were significantly lower at first sampling, while sperm vitality and morphology were not affected. The total sperm count, sperm concentration, and number of motile spermatozoa per ejaculate were significantly increased and the percentage of morphologically abnormal sperm was reduced at the second sampling compared with those at first in the 22 patients examined. Though there were higher prolactin and lower progesterone levels in patients at first sampling than those in controls, no significant alterations were detected for any sex hormones examined over time following COVID-19 recovery in the 22 patients. Although it should be interpreted carefully, these findings indicate an adverse but potentially reversible consequence of COVID-19 on sperm quality.

Journal ArticleDOI
TL;DR: The escalating prevalence of male infertility and decreasing trend in sperm quality have been correlated with rapid industrialisation and the associated discharge of an excess of synthetic substances into the environment and the possible mechanisms of action are discussed.
Abstract: The escalating prevalence of male infertility and decreasing trend in sperm quality have been correlated with rapid industrialisation and the associated discharge of an excess of synthetic substances into the environment. Humans are inevitably exposed to these ubiquitously distributed environmental contaminants, which possess the ability to intervene with the growth and function of male reproductive organs. Several epidemiological reports have correlated the blood and seminal levels of environmental contaminants with poor sperm quality. Numerous in vivo and in vitro studies have been conducted to investigate the effect of various environmental contaminants on spermatogenesis, steroidogenesis, Sertoli cells, blood-testis barrier, epididymis and sperm functions. The reported reprotoxic effects include alterations in the spermatogenic cycle, increased germ cell apoptosis, inhibition of steroidogenesis, decreased Leydig cell viability, impairment of Sertoli cell structure and function, altered expression of steroid receptors, increased permeability of blood-testis barrier, induction of peroxidative and epigenetic alterations in spermatozoa resulting in poor sperm quality and function. In light of recent scientific reports, this review discusses the effects of environmental contaminants on the male reproductive function and the possible mechanisms of action.

Journal ArticleDOI
TL;DR: In this paper, the authors demonstrate that a folate-deficient diet exacerbates histone H3 lysine 4 trimethylation (H3K4me3) in sperm at developmental genes and putative enhancers.

Journal ArticleDOI
TL;DR: This largest study with comprehensive evaluation of semen quality and reproductive function, etiology and risk factor determination, and metabolic, cardiovascular, and osteoporosis risk assessment in men referred for fertility evaluation showed that a man's semen count is a marker of his general health.
Abstract: Background Some evidence suggests that infertile men, who are at increased risk for hypogonadism, metabolic derangements, and osteoporosis, have higher long-term morbidity and mortality than controls, but data are scarce and not conclusive. Objective We tested whether semen quality and reproductive function could represent a marker of general male health. Design, setting, and participants A retrospective study of 5177 individuals from a prospectively collected database of 11 516 males of infertile couples who had semen analysis in a tertiary university center. Outcome measurements and statistical analysis Of them, 5177 had all data for reproductive hormones, testis ultrasound, and biochemical determinations for glucose and lipid metabolism. Hypogonadism was defined as testosterone 9.4 IU/l. Individuals with a total sperm count of Results and limitations Men with a low sperm count ( Conclusions This is the largest study with comprehensive evaluation of semen quality and reproductive function, etiology and risk factor determination, and metabolic, cardiovascular, and osteoporosis risk assessment, performed in men referred for fertility evaluation. A low sperm count is associated with poorer metabolic, cardiovascular, and bone health. Hypogonadism is mainly involved in this association, but a low sperm count in itself is a marker of general health. Patient summary This large study evaluated semen quality, reproductive function, and metabolic risk in men referred for fertility evaluation, and showed that a man’s semen count is a marker of his general health. Men with low sperm counts are more likely than those with normal sperm counts to have greater body fat, higher blood pressure, higher “bad” (low-density lipoprotein) cholesterol and triglycerides, and lower “good” (high-density lipoprotein) cholesterol. They also have a higher frequency of metabolic syndrome and insulin resistance, a condition that can lead to diabetes. Men with low sperm counts had a 12-fold increased risk of hypogonadism or low testosterone levels, and half of them had osteoporosis or low bone mass. Fertility evaluation gives men the unique opportunity for health assessment and disease prevention.

Journal ArticleDOI
TL;DR: The mechanisms of DNA damage as well as its impact in different scenarios of male infertility, associated with spontaneous and assisted reproduction and the clinical applicability of sperm DNA fragmentation testing are discussed.
Abstract: Male factor is responsible for up to 50% of infertility cases in the world Semen analysis is considered the cornerstone of laboratory evaluation of male infertility, but it has its own drawbacks and fails to predict the male fertility potential with high sensitivity and specificity Different etiologies have been linked with male infertility, of which sperm DNA damage has gained significant attention with extensive research on sperm function tests The associations between sperm DNA damage and a variety of disorders such as varicocele, obesity, cancer, radiation and lifestyle factors are explored in this review Furthermore, we discuss the mechanisms of DNA damage as well as its impact in different scenarios of male infertility, associated with spontaneous and assisted reproduction Finally, we review the clinical applicability of sperm DNA fragmentation testing in the management of male infertility

Journal ArticleDOI
TL;DR: It is proposed that high concentrations of seminal leukocyte and infectious agents may affect sperm function resulting in clumping of motile spermatozoa, decreasing acrosomal functionality and also causing alterations in sperm morphology.
Abstract: Declining birth rates are one of the problems facing society today. Male counterparts are responsible for about half of the infertility cases, and genitourinary tract infections may play a contributing role in approximately 15% of male infertility cases. Leukocytospermia is an established indicator of infection in the male urogenital tract, although other microorganisms such as bacteria and virus may also be contributors to the etiology of male infertility. The pathophysiology of these infectious agents may be initiated by a local inflammatory reaction resulting in an increase in reactive oxygen species (ROS). This results in testicular injury, thereby affecting sperm morphology, sperm motility, sperm viability and elevation of the seminal leukocyte as a result of the genital tract infection. The infectious and inflammatory changes can result in male infertility. It is proposed that high concentrations of seminal leukocyte and infectious agents may affect sperm function resulting in clumping of motile spermatozoa, decreasing acrosomal functionality and also causing alterations in sperm morphology. However, the literature has poorly clarified the role of infection in male infertility, provoking further debate and research on this topic.

Journal ArticleDOI
TL;DR: Exposure to polystyrene microplastics led to the damage of seminiferous tubule, resulted in apoptosis of spermatogenic cell and decreased the motility and concentration of sperm, while the abnormality of sperm was elevated and demonstrated that high-dose PS-MPs exposure may lead to the destruction of BTB integrity and the apoptosis to the activation of MAPK-Nrf2 pathway.
Abstract: As a persistent pollutant, microplastics (MPs) have been reported to induce sperm quantity decrease in mice. However, the related mechanism remains obscure. Therefore, this study is intended to explore the effects of polystyrene microplastics (PS-MPs) on male reproduction and its related mechanism of blood-testis barrier (BTB) impairment. Thirty-two adult male Wistar rats were divided randomly into four groups fed with PS-MPs for 90 days at doses of 0 mg/day (control group), 0.015 mg/day, 0.15 mg/day, and 1.5 mg/day, respectively. The present results have shown that PS-MP exposure led to the damage of seminiferous tubule, resulted in apoptosis of spermatogenic cells, and decreased the motility and concentration of sperm, while the abnormality of sperm was elevated. Meanwhile, PS-MPs could induce oxidative stress and activate the p38 MAPK pathway and thus deplete the nuclear factor erythroid-2 related factor 2 (Nrf2). Noteworthily, PS-MPs led to the BTB-related protein expression decrease. All these results demonstrated that PS-MP exposure may lead to the destruction of BTB integrity and the apoptosis of spermatogenic cells through the activation of the MAPK-Nrf2 pathway. The current study provided novelty evidence for elucidating the effects of PS-MPs on male reproductive toxicity and its potential mechanism.

Journal ArticleDOI
TL;DR: In this article, the authors investigated whether intracytoplasmic sperm injection would result in a higher live birth rate compared with conventional IVF and found that it did not improve the livebirth rate in couples with non-male factor infertility.

Journal ArticleDOI
TL;DR: CoQ10 supplementation for three months could improve semen parameters, oxidative stress markers and reduce SDF in infertile men with idiopathic OA.
Abstract: PURPOSE Oxidative stress and sperm DNA fragmentation (SDF) are potential contributing factors for idiopathic male infertility. Coenzyme Q10 (CoQ10) have been reported to be effective in the treatment of idiopathic male infertility, in general, owing to its antioxidant properties. Thus, the present study intends to investigate the effects of CoQ10 therapy on semen parameters, oxidative stress markers and SDF in infertile men, specifically with idiopathic oligoasthenozoospermia (OA). MATERIALS AND METHODS In this case-control study, sixty-five infertile patients with idiopathic OA and forty fertile men (control) were included. All participants underwent semen analysis based on the World Health Organization guidelines (5th edition, 2010). Patients received CoQ10 at the dose of 200 mg/d orally for three months. Seminal plasma CoQ10, total antioxidant capacity (TAC), total reactive oxygen species (ROS), glutathione peroxidase (GPx), and SDF levels were measured in controls (baseline) and infertile patients pre- and post-CoQ10 treatment. RESULTS CoQ10 treatment for three months significantly improved sperm concentration (p<0.05), progressive motility (p<0.05), total motility (p<0.01), seminal fluid CoQ10 concentration (p<0.001), TAC (p<0.001), and GPx (p<0.001) levels in infertile men with OA. Further, ROS level (p<0.05) and SDF percentage (p<0.001) were reduced in OA patients as compared to the baseline. CoQ10 levels also correlated positively with sperm concentration (r=0.48, p=0.01) and total motility (r=0.59, p=0.003) while a negative correlation was recorded between SDF and sperm motility (r=-0.54, p=0.006). CONCLUSIONS CoQ10 supplementation for three months could improve semen parameters, oxidative stress markers and reduce SDF in infertile men with idiopathic OA.

Journal ArticleDOI
TL;DR: A detailed overview of OMICS elements involved in sperm cryo-tolerance and freeze-thawed quality can be found in this paper, where the sperm freezability biomarkers are used to compare the sperm freezing performance.
Abstract: Sperm cryopreservation is a powerful tool for the livestock breeding program. Several technical attempts have been made to enhance the efficiency of spermatozoa cryopreservation in different farm animal species. However, it is well-recognized that mammalian spermatozoa are susceptible to cryo-injury caused by cryopreservation processes. Moreover, the factors leading to cryo-injuries are complicated, and the cryo-damage mechanism has not been methodically explained until now, which directly influences the quality of frozen-thawed spermatozoa. Currently, the various OMICS technologies in sperm cryo-biology have been conducted, particularly proteomics and transcriptomics studies. It has contributed while exploring the molecular alterations caused by cryopreservation, identification of various freezability markers and specific proteins that could be added to semen diluents before cryopreservation to improve sperm cryo-survival. Therefore, understanding the cryo-injury mechanism of spermatozoa is essential for the optimization of current cryopreservation processes. Recently, the application of newly-emerged proteomics and transcriptomics technologies to study the effects of cryopreservation on sperm is becoming a hotspot. This review detailed an updated overview of OMICS elements involved in sperm cryo-tolerance and freeze-thawed quality. While also detailed a mechanism of sperm cryo-injury and utilizing OMICS technology that assesses the sperm freezability potential biomarkers as well as the accurate classification between the excellent and poor freezer breeding candidate.

Journal ArticleDOI
TL;DR: In this article, male and female C57BL/6 mice were exposed to saline or 0.1 mg/d polystyrene microplastics for 30 days or 44 days to determine the effects of MPs on reproductive systems, following which some of the mice were caged for 10 days to mate to test fertility.

Journal ArticleDOI
TL;DR: For example, this article found that sustained cannabis abstinence significantly reduced the number of sperm showing cannabis-associated alterations at genes important for early development, including cardiogenesis and neurodevelopment.
Abstract: Cannabis use alters sperm DNA methylation, but the potential reversibility of these changes is unknown. Semen samples from cannabis users and non-user controls were collected at baseline and again following a 77-day period of cannabis abstinence (one spermatogenic cycle). Users and controls did not significantly differ by demographics or semen analyses. Whole-genome bisulfite sequencing identified 163 CpG sites with significantly different DNA methylation in sperm between groups (P < 2.94 × 10-9). Genes associated with altered CpG sites were enriched with those involved in development, including cardiogenesis and neurodevelopment. Many of the differences in sperm DNA methylation between groups were diminished after cannabis abstinence. These results indicate that sustained cannabis abstinence significantly reduces the number of sperm showing cannabis-associated alterations at genes important for early development.

Journal ArticleDOI
TL;DR: A multicenter study is promoted to assess the CDUS characteristics of healthy fertile men (HFM) to obtain normative parameters to obtain standardization parameters.
Abstract: Background Scrotal color Doppler ultrasound (CDUS) still suffers from lack of standardization. Hence, the European Academy of Andrology (EAA) has promoted a multicenter study to assess the CDUS characteristics of healthy fertile men (HFM) to obtain normative parameters. Objectives To report and discuss the scrotal organs CDUS reference ranges and characteristics in HFM and their associations with clinical, seminal, and biochemical parameters. Methods A cohort of 248 HFM (35.3 ± 5.9years) was studied, evaluating, on the same day, clinical, biochemical, seminal, and scrotal CDUS following Standard Operating Procedures. Results The CDUS reference range and characteristics of the scrotal organs of HFM are reported here. CDUS showed a higher accuracy than physical examination in detecting scrotal abnormalities. Prader orchidometer (PO)- and US-measured testicular volume (TV) were closely related. The US-assessed TV with the ellipsoid formula showed the best correlation with the PO-TV. The mean TV of HFM was ~ 17 ml. The lowest reference limit for right and left testis was 12 and 11 ml, thresholds defining testicular hypotrophy. The highest reference limit for epididymal head, tail, and vas deferens was 12, 6, and 4.5 mm, respectively. Mean TV was associated positively with sperm concentration and total count and negatively with gonadotropins levels and pulse pressure. Subjects with testicular inhomogeneity or calcifications showed lower sperm vitality and concentration, respectively, than the rest of the sample. Sperm normal morphology and progressive motility were positively associated with epididymal head size/vascularization and vas deferens size, respectively. Increased epididymis and vas deferens sizes were associated with MAR test positivity. Decreased epididymal tail homogeneity/vascularization were positively associated with waistline, which was negatively associated with intratesticular vascularization. CDUS varicocele was detected in 37.2% of men and was not associated with seminal or hormonal parameters. Scrotal CDUS parameters were not associated with time to pregnancy, number of children, history of miscarriage. Conclusions The present findings will help in better understanding male infertility pathophysiology, improving its management.

Journal ArticleDOI
31 Mar 2021-Nature
TL;DR: This paper showed that the endopeptidases ECS1 and ESC2 are secreted to the extracellular space from a cortical network located at the apical domain of the Arabidopsis egg cell after successful fertilization.
Abstract: Upon gamete fusion, animal egg cells secrete proteases from cortical granules to establish a fertilization envelope as a block to polyspermy1–4. Fertilization in flowering plants is more complex and involves the delivery of two non-motile sperm cells by pollen tubes5,6. Simultaneous penetration of ovules by multiple pollen tubes (polytubey) is usually avoided, thus indirectly preventing polyspermy7,8. How plant egg cells regulate the rejection of extra tubes after successful fertilization is not known. Here we report that the aspartic endopeptidases ECS1 and ECS2 are secreted to the extracellular space from a cortical network located at the apical domain of the Arabidopsis egg cell. This reaction is triggered only after successful fertilization. ECS1 and ECS2 are exclusively expressed in the egg cell and transcripts are degraded immediately after gamete fusion. ECS1 and ESC2 specifically cleave the pollen tube attractor LURE1. As a consequence, polytubey is frequent in ecs1 ecs2 double mutants. Ectopic secretion of these endopeptidases from synergid cells led to a decrease in the levels of LURE1 and reduced the rate of pollen tube attraction. Together, these findings demonstrate that plant egg cells sense successful fertilization and elucidate a mechanism as to how a relatively fast post-fertilization block to polytubey is established by fertilization-induced degradation of attraction factors. Fertilized Arabidopsis egg cells secrete endopeptidases into the extracellular space that cleave the pollen tube attractor LURE1, preventing polytubey.

Journal ArticleDOI
TL;DR: Treatment with coenzyme Q10 or selenium could improve sperm concentration, motility, and antioxidant status in infertile men with idiopathic OAT with CoQ10 providing the higher improvement.
Abstract: Oxidative stress (OS) is a key contributing factor in 30–80% of male infertility cases To date, several antioxidant treatments have been put forth to manage OS-induced male infertility This study intended to elucidate the impact of coenzyme Q10 (CoQ10) and selenium on seminal fluid parameters and antioxidant status in infertile men with idiopathic oligoasthenoteratospermia (OAT) In this prospective study, 70 patients with idiopathic OAT were randomly allocated to receive CoQ10 (200 mg/day) or selenium (200 μg/day) for 3 months Semen quality parameters (following WHO guidelines, 5th edition), total antioxidant capacity (TAC), catalase (CAT), and superoxide dismutase (SOD) activities were compared before and after the treatment The results of the study showed an increase in sperm concentration with CoQ10 treatment (p < 001) as well as increased progressive sperm motility (p < 001 and p < 005) and total sperm motility (p < 001 and p < 005) with CoQ10 and selenium treatment respectively There was also a significant improvement in TAC (p < 001 and p < 005) and SOD (p < 001 and p < 005) following treatment with CoQ10 and selenium respectively while CAT improved only with CoQ10 therapy (p < 005) Sperm concentration, motility, and morphology also correlated significantly with TAC, SOD, and CAT (r = 037–076) In conclusion, treatment with CoQ10 (200 mg) or selenium (200 μg) could improve sperm concentration, motility, and antioxidant status in infertile men with idiopathic OAT with CoQ10 providing the higher improvement

Journal ArticleDOI
TL;DR: A review of sperm DNA base oxidation and its associated genetic and epigenetic consequences can be found in this paper, with the focus on single-and double-strand paternal DNA breaks.
Abstract: One important reason for male infertility is oxidative stress and its destructive effects on sperm structures and functions. The particular composition of the sperm membrane, rich in polyunsaturated fatty acids, and the easy access of sperm DNA to oxidative damage due to sperm cell specific cytologic and metabolic features (no cytoplasm left and cells unable to mount stress responses) make it the cell type in metazoans most susceptible to oxidative damage. In particular, oxidative damage to the spermatozoa genome is an important issue and a cause of male infertility, usually associated with single- or double-strand paternal DNA breaks. Various methods of detecting sperm DNA fragmentation have become important diagnostic tools in the prognosis of male infertility and such assays are available in research laboratories and andrology clinics. However, to date, there is not a clear consensus in the community as to their respective prognostic value. Nevertheless, it is important to understand that the effects of oxidative stress on the sperm genome go well beyond DNA fragmentation alone. Oxidation of paternal DNA bases, particularly guanine and adenosine residues, the most sensitive residues to oxidative alteration, is the starting point for DNA damage in spermatozoa but is also a danger for the integrity of the embryo genetic material independently of sperm DNA fragmentation. Due to the lack of a spermatozoa DNA repair system and, if the egg is unable to correct the sperm oxidized bases, the risk of de novo mutation transmission to the embryo exists. These will be carried on to every cell of the future individual and its progeny. Thus, in addition to affecting the viability of the pregnancy itself, oxidation of the DNA bases in sperm could be associated with the development of conditions in young and future adults. Despite these important issues, sperm DNA base oxidation has not attracted much interest among clinicians due to the lack of simple, reliable, rapid and consensual methods of assessing this type of damage to the paternal genome. In addition to these technical issues, another reason explaining why the measurement of sperm DNA oxidation is not included in male fertility is likely to be due to the lack of strong evidence for its role in pregnancy outcome. It is, however, becoming clear that the assessment of DNA base oxidation could improve the efficiency of assisted reproductive technologies and provide important information on embryonic developmental failures and pathologies encountered in the offspring. The objective of this work is to review relevant research that has been carried out in the field of sperm DNA base oxidation and its associated genetic and epigenetic consequences.

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TL;DR: In this paper, a prospective cohort study was conducted at a single large tertiary centre in Israel between February and March of 2021, where semen samples from 75 fertile men were analyzed 1-2 months following their second dose of Pfizer's COVID-19 vaccine.
Abstract: Research question Does Pfizer's coronavirus disease 2019 (COVID-19) vaccination detrimentally affect semen analysis parameters? Design A prospective cohort study was conducted at a single large tertiary centre in Israel between February and March of 2021. Semen samples from 75 fertile men were analysed 1–2 months following their second dose of Pfizer's COVID-19 vaccine. The semen parameters were compared with the World Health Organization (WHO) reference ranges. The primary outcome was the percentage of abnormal semen parameters in those who were vaccinated, i.e. the rates of oligozoospermia, reduced percentage of motile spermatozoa and abnormal sperm morphology. Results The interval from the time of the second vaccination to the date of participation was on average 37 days, with most subjects describing either mild or no side effects after the first or second dose. The mean sperm concentration was 63.2 ± 33.6 × 106/ml, with only a single participant (1.3%) with a sperm count of 12.5 × 106/ml, considered by the WHO to be oligozoospermic. The mean sperm motility percentage was 64.5 ± 16.7%, with only a single man (1.3%) displaying reduced motility. No notable morphological abnormalities were observed. This constituted a lower percentage of abnormal semen parameters compared with the 5% rates reported in fertile men by the WHO. Conclusions The semen parameters following COVID-19 vaccination were predominantly within the normal reference ranges as set by the WHO and do not reflect any causative detrimental effect from COVID-19 vaccination. The results strengthen the notion that the Pfizer's severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine is safe and should be recommended to men wishing to conceive.

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TL;DR: In this paper, the authors integrate single-molecule long-read sequencing with short read sequencing to detect sperm intact RNAs (spiRNAs) and identify 3440 spiRNA species in mice and 4100 in humans.
Abstract: Sperm contributes diverse RNAs to the zygote. While sperm small RNAs have been shown to impact offspring phenotypes, our knowledge of the sperm transcriptome, especially the composition of long RNAs, has been limited by the lack of sensitive, high-throughput experimental techniques that can distinguish intact RNAs from fragmented RNAs, known to abound in sperm. Here, we integrate single-molecule long-read sequencing with short-read sequencing to detect sperm intact RNAs (spiRNAs). We identify 3440 spiRNA species in mice and 4100 in humans. The spiRNA profile consists of both mRNAs and long non-coding RNAs, is evolutionarily conserved between mice and humans, and displays an enrichment in mRNAs encoding for ribosome. In sum, we characterize the landscape of intact long RNAs in sperm, paving the way for future studies on their biogenesis and functions. Our experimental and bioinformatics approaches can be applied to other tissues and organisms to detect intact transcripts.

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25 Jan 2021-eLife
TL;DR: Borg et al. as discussed by the authors examined the epigenetics of pollen in Arabidopsis thaliana, a widely studied plant and common weed, and revealed how the loss of DNA and histone methylation are important for plants to reproduce sexually via pollen.
Abstract: Each pollen grain from a flowering plant houses sperm, which contain half of the genes needed to make a new plant, and a companion or vegetative cell (VC) that serves to deliver sperm to the egg. The genes in the vegetative cell and those in the sperm are identical to the genes of the plant they come from, so how can this set of identical genetic information produce such different cells? Both DNA and histones, the proteins that pack and order DNA, can be chemically modified locally through a process called methylation. The location of these modifications can affect how genetic information in the DNA is read to make different types of cells. The use of processes like methylation to regulate whether genes are switched on or off is called epigenetics. So what role does epigenetics play in plant pollen? To answer this question, Borg et al. examined the epigenetics of pollen in Arabidopsis thaliana, a widely studied plant and common weed. In vegetative cells, DNA methylation is lost together with a different methylation mark (H3K9me2), which unlocks several genes needed for pollen to transport sperm. By contrast, sperm loses an entirely different methylation mark, called H3K27me3, which unlocks a different set of genes that help to prepare development of a new plant once sperm fertilizes the egg. Through these different set of epigenetic changes, activity increases at different groups of genes that are important for shaping the function of each pollen cell type. These results reveal how the loss of DNA and histone methylation are important for plants to reproduce sexually via pollen. This offers insights into the evolution of plants and other related life forms. Learning about plant reproduction may also help to increase food production by improving crop yields.

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TL;DR: This synthesized group of artificial octoploids provides a unique case to explore the effect of sex determination system incorporation on reproduction mode transition from unisexual gynogenesis to sexual reproduction along with genome synthesis of recurrent polyploidy in vertebrates.
Abstract: Polyploids in vertebrates are generally associated with unisexual reproduction, but the direct consequences of polyploidy on sex determination system and reproduction mode remain unknown. Here, we synthesized a group of artificial octoploids between unisexual gynogenetic hexaploid Carassius gibelio and sexual tetraploid Carassius auratus. The synthetic octoploids were revealed to have more than 200 chromosomes, in which 50 chromosomes including the X/Y sex determination system were identified to transfer from sexual tetraploid C. auratus into the unisexual gynogenetic hexaploid C. gibelio. Significantly, a few synthetic octoploid males were found to be fertile, and one octoploid male was confirmed to regain sexual reproduction ability, which exhibits characteristics that are the same to sexual reproduction tetraploid males, such as 1:1 sex ratio occurrence, meiosis completion and euploid sperm formation in spermatogenesis, as well as normal embryo development and gene expression pattern during embryogenesis. Therefore, the current finding provides a unique case to explore the effect of sex determination system incorporation on reproduction mode transition from unisexual gynogenesis to sexual reproduction along with genome synthesis of recurrent polyploidy in vertebrates.