-
Clinical and Experimental Reproductive... Jun 2021Male infertility has a complex etiopathology, which mostly remains elusive. Although research has claimed that oxidative stress (OS) is the most likely underlying...
Male infertility has a complex etiopathology, which mostly remains elusive. Although research has claimed that oxidative stress (OS) is the most likely underlying mechanism of idiopathic male infertility, the specific treatment of OS-mediated male infertility requires further investigation. Coenzyme Q10 (CoQ10), a vitamin-like substance, has been found in measurable levels in human semen. It exhibits essential metabolic and antioxidant functions, as well as playing a vital role in mitochondrial bioenergetics. Thus, CoQ10 may be a key player in the maintenance of biological redox balance. CoQ10 concentrations in seminal plasma directly correlate with semen parameters, especially sperm count and sperm motility. Seminal CoQ10 concentrations have been shown to be altered in various male infertility states, such as varicocele, asthenozoospermia, and medical or surgical regimens used to treat male infertility. These observations imply that CoQ10 plays an important physiological role in the maintenance and amelioration of semen quality. The present article thereby aimed to review the possible mechanisms through which CoQ10 plays a role in the regulation of male reproductive function, and to concisely discuss its efficacy as an ameliorative agent in restoring semen parameters in male infertility, as well as its impact on OS markers, sperm DNA fragmentation, pregnancy, and assisted reproductive technology outcomes.
PubMed: 34078005
DOI: 10.5653/cerm.2020.04175 -
Scientific Reports Dec 2022Men in couples that have experienced pregnancy loss have a higher risk of sexual dysfunction. Semen quality impairment is common in men of couples with pregnancy loss....
Men in couples that have experienced pregnancy loss have a higher risk of sexual dysfunction. Semen quality impairment is common in men of couples with pregnancy loss. The objective of this article is to evaluate the differences in the incidence of male sexual dysfunction in a cohort of pregnancy loss couples with different types of semen quality impairment. A cross-sectional analysis of 426 men who attended our outpatient clinic for couples' pregnancy loss, those without genetic abnormalities were included in the final analysis covering June 2021 to October 2021. The patients were divided into 5 groups according to type of semen quality impairment: normozoospermia group (group normal; N = 161), high sperm DNA fragmentation group (group high-SDF; N = 87), isolated asthenozoospermia group (group iAstheno; N = 45), isolated teratozoopermia group (group iTerato; N = 44), and ≥ 2 abnormal sperm parameters group (group multiple; N = 89). All subjects underwent a complete physical inspection, including palpation of the male genitalia and semen analysis. Validated assessment tools for erectile dysfunction (the International Index of Erectile Function -IIEF-5) and anxiety (the seven-item Generalized Anxiety Disorder Scale- GAD-7) were also used. Men with high sperm DNA fragmentation and isolated teratozoopermia were associated with increased erectile dysfunction risk when compared with normozoospermic men, with an OR of 2.75 [1.49-5.09; p = 0.001] and 2.44 [1.22-5.31; p = 0.024], respectively. It is interesting to note that there was no difference in prevalence of erectile dysfunction between Group iAstheno and Group normal (20.0% vs. 18.0%; OR = 1.24 [0.52-2.97]; P = 0.625). More than half (50.6%) of the participants in Group high-SDF reported sexual intercourse less than once per week, much more than those in the normozoospermia group (23.2%, p < 0.05), followed by Group iTerato (44.4%) and Group multiple (46.1%). GAD-7 scores increased slightly but significantly among groups when compared with Group normal. Not surprisingly, GAD-7 scores remained higher in Group high-SDF. In males of pregnancy loss couples, men with high sperm DNA fragmentation and teratozoopermia suffer from a higher incidence of erectile dysfunction. This phenomenon is not significant in men with isolated asthenozoospermia. Proper counseling and treatment of impaired semen quality are warranted.
Topics: Humans; Male; Semen Analysis; Erectile Dysfunction; DNA Fragmentation; Asthenozoospermia; Cross-Sectional Studies; Semen; Spermatozoa; Infertility, Male
PubMed: 36575203
DOI: 10.1038/s41598-022-27006-z -
Frontiers in Endocrinology 2021Currently, the molecular mechanisms underlining male infertility are still poorly understood. Our previous study has demonstrated that PIWI-interacting RNAs (piRNAs) are...
Currently, the molecular mechanisms underlining male infertility are still poorly understood. Our previous study has demonstrated that PIWI-interacting RNAs (piRNAs) are downregulated in seminal plasma of infertile patients and can serve as molecular biomarkers for male infertility. However, the source and mechanism for the dysregulation of piRNAs remain obscure. In this study, we found that exosomes are present in high concentrations in human seminal plasma and confirmed that piRNAs are predominantly present in the exosomal fraction of seminal plasma. Moreover, we showed that piRNAs were significantly decreased in exosomes of asthenozoospermia patients compared with normozoospermic men. By systematically screening piRNA profiles in sperms of normozoospermic men and asthenozoospermia patients, we found that piRNAs were parallelly reduced during infertility. At last, we investigated the expression of some proteins that are essential for piRNAs biogenesis in sperms and therefore identified a tight correlation between the levels of spermatozoa piRNA and MitoPLD protein, suggesting that the loss-of-function of MitoPLD could cause a severe defect of piRNA accumulation in sperms. In summary, this study identified a parallel reduction of piRNAs and MitoPLD protein in sperms of asthenozoospermia patients, which may provide pathophysiological clues about sperm motility.
Topics: Adult; Asthenozoospermia; Case-Control Studies; Down-Regulation; Exosomes; Gene Expression Profiling; High-Throughput Nucleotide Sequencing; Humans; Infertility, Male; Male; Mitochondrial Proteins; Phospholipase D; RNA, Small Interfering; Semen; Semen Analysis; Sequence Analysis, RNA
PubMed: 34326815
DOI: 10.3389/fendo.2021.696121 -
Biomedicines Jan 2024VPS13A, also known as chorein, whose loss of function causes chorea-acanthocytosis (ChAc), is characterized by Huntington's-disease-like neurodegeneration and...
VPS13A, also known as chorein, whose loss of function causes chorea-acanthocytosis (ChAc), is characterized by Huntington's-disease-like neurodegeneration and neuropsychiatric symptoms in addition to acanthocytosis in red blood cells. We previously reported that ChAc-model mice with a loss of chorein function exhibited male infertility, with asthenozoospermia and mitochondrial dysmorphology in the spermatozoa. Here, we report a novel aspect of chorein dysfunction in male fertility, particularly its role in spermatogenesis and mitochondrial integrity. An increase in anti-malondialdehyde antibody immunoreaction within the testes, predominantly observed at the advanced stages of sperm formation in chorein-deficient mice, suggests oxidative stress as a contributing factor to mitochondrial dysfunction and impaired sperm maturation. The chorein immunoreactivity in spermatids of wild-type mice accentuates its significance in sperm development. ChAc-model mice exhibit mitochondrial ultrastructural abnormalities, specifically during the late stages of sperm maturation, suggesting a critical timeframe for chorein's action in spermiogenesis. We observed an increase in TOM20 protein levels, indicative of disrupted mitochondrial import mechanisms. The concurrent decrease in metabolic enzymes such as IDH3A, LDHC, PGK2, and ACAT1 suggests a complex chorein-mediated metabolic network that is essential for sperm vitality. Additionally, heightened separation of cytoplasmic droplets from sperm highlights the potential membrane instability in chorein-deficient spermatozoa. Metabolomic profiling further suggests a compensatory metabolic shift, with elevated glycolytic and TCA-cycle substrates. Our findings suggest that chorein is involved in anti-ferroptosis and the maturation of mitochondrial morphology in the late stages of spermatogenesis, and its deficiency leads to asthenozoospermia characterized by membrane instability, abnormal cytosolic glycolysis, abnormal mitochondrial function, and a disrupted TCA cycle. Further analyses are required to unravel the molecular mechanisms that directly link these findings and to elucidate the role of chorein in spermatogenesis as well as its broader implications.
PubMed: 38275411
DOI: 10.3390/biomedicines12010240 -
Medicine Jan 2021Infertility has affected millions of couples aged 15 to 44 years worldwide. Recently, some studies suggest that abnormal semen quality is the main cause of male...
INTRODUCTION
Infertility has affected millions of couples aged 15 to 44 years worldwide. Recently, some studies suggest that abnormal semen quality is the main cause of male infertility and asthenozoospermia accounts for 19% of the infertility of men. The situation has brought a huge burden to the patient with asthenozoospermia and society. Acupuncture is a part of traditional Chinese medicine. Electroacupuncture (EA) has gained in popularity. Although a positive effect of manual acupuncture and EA on sperm parameters has been documented in several studies, there still a lack of more solid evidence. We hope to provide a convincing study for EA.
METHODS AND ANALYSIS
The electronic databases of MEDLINE, PubMed, Web of Science, EMBASE, Cochrane Library, Clinicaltrials. org, China National Knowledge Infrastructure Database (CNKI), Wan fang Database, China Biology Medicine Database (CBM), VIP Science Technology Periodical Database, Chinese Clinical Trial Registry will be retrieved. All the randomized controlled trials of rESWT for patients with CP/CPPS will be included. We will evaluate the outcomes including NIH-CPSI, VAS, IPSS, IIEF-5, and conduct this study strictly according to the Cochrane Handbook for Systematic Reviews of Interventions.
RESULTS
The present study is a protocol for systematic review and meta-analysis without results, and data analysis will be carried out after the protocol. We will share our findings on October 31st, 2021.
CONCLUSIONS
EA for asthenospermia is a microtrauma surgery with less pain. EA can effectively improve sperm motility; however, its efficacy has not been assessed scientifically and systematically. To address this limitation, this study will inspect the efficacy and safety of the EA in patients with asthenospermia.
ETHICS AND DISSEMINATION
Formal ethical approval is not required in this protocol. We will collect and analyze data based on published studies, and since there are no patients involved in this study, individual privacy will not be under concerns. The results of this review will be disseminated to peer-reviewed journals or submit to related conferences.
PROTOCOL REGISTRATION NUMBER
INPLASY2020100071.
Topics: Adolescent; Adult; Asthenozoospermia; Electroacupuncture; Humans; Male; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Research Design; Semen Analysis; Systematic Reviews as Topic; Treatment Outcome; Young Adult
PubMed: 33530158
DOI: 10.1097/MD.0000000000023350 -
Journal of Personalized Medicine Jul 2021Infertility is one of the important problems in the modern world. Male infertility is characterized by several clinical manifestations, including low sperm production...
Infertility is one of the important problems in the modern world. Male infertility is characterized by several clinical manifestations, including low sperm production (oligozoospermia), reduced sperm motility (asthenozoospermia), and abnormal sperm morphology (teratozoospermia). known as Wuho, controls fertility in Drosophila. However, it is unclear whether is associated with clinical manifestations of male fertility in human. Here, we attempted to determine the physiological functions of gene. Two cohorts were applied to address this question. The first cohort was the general population from Taiwan Biobank. Genomic profiles from 68,948 individuals and 87 common physiological traits were applied for phenome-wide association studies (PheWAS). The second cohort comprised patients with male infertility from Wan Fang Hospital, Taipei Medical University. In total, 81 male participants were recruited for the genetic association study. Clinical records including gender, age, total testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total sperm number, sperm motility, and sperm morphology were collected. In the first cohort, results from PheWAS exhibited no associations between genetic variants and 87 common physiological traits. In the second cohort, a total of four tagging single-nucleotide polymorphisms (tSNPs) from gene (rs2298666, rs465663, rs2248490, and rs3746939) were selected for genotyping. We found that SNP rs465663 solely associated with asthenozoospermia. Functional annotations through the GTEx portal revealed the correlation between TT or TC genotype and low expression of . Furthermore, we used mouse embryonic fibroblasts cells from mwdr4 heterozygous (+/‒) mice for functional validation by western blotting. Indeed, low expression of WDR4 contributed to ROS-induced DNA fragmentation. In conclusion, our results suggest a critical role of gene variant as well as protein expression in asthenozoospermia.
PubMed: 34442404
DOI: 10.3390/jpm11080760 -
Basic and Clinical Andrology Apr 2022Severe or complete asthenozoospermia is a rare entity that can lead to male infertility. In this study, we explored whether different extents of severe or complete...
BACKGROUND
Severe or complete asthenozoospermia is a rare entity that can lead to male infertility. In this study, we explored whether different extents of severe or complete asthenozoospermia could affect intracytoplasmic sperm injection (ICSI) outcomes and compared the ICSI outcomes using testicular spermatozoa with those using ejaculated spermatozoa in couples with complete asthenozoospermia.
RESULTS
Ninety-seven couples with severe or complete asthenozoospermia who underwent ICSI between January 2014 and December 2018 were included. According to the sperm category used in ICSI, patients were categorized into four groups: ejaculated progressive motile sperm group (Ep-group), ejaculated non-progressive motile sperm group (En-group), ejaculated immotile sperm group (Ei-group), and testicular sperm group (TESE-group). We compared the baseline characteristics, hormone profile, semen parameters, normal fertilization, good-quality embryos on day 3, transferred embryos, and ICSI outcomes in the four groups. The clinical pregnancy rate was significantly increased in the Ep-group (65.4%, P = 0.019) and TESE-group (63.6%, P = 0.035) compared with that in the Ei-group (23.1%). The ongoing pregnancy rate in the Ei-group was significantly lower than that in the Ep-group (23.1% vs. 61.5%, P = 0.041). Moreover, the biochemical pregnancy rate, ongoing pregnancy rate, and live birth rate were much lower in the Ei-group than in the TESE-group (30.8% vs. 63.6%, 23.1% vs. 40.4% and 23.1% vs. 40.4%, respectively).
CONCLUSIONS
In couples with complete asthenozoospermia, testicular spermatozoa should be preferred to ejaculated spermatozoa for obtaining a better ICSI outcome. With the appropriate selection of testicular spermatozoa, the extent of severe or complete asthenozoospermia may not affect the ICSI outcomes. Future studies with a larger sample size are warranted to validate these findings.
PubMed: 35382740
DOI: 10.1186/s12610-022-00155-x -
Frontiers in Endocrinology 2020The role of circRNA in reproduction is under investigation. CircRNAs are expressed in human testis, spermatozoa (SPZ), and seminal plasma. Their involvement in embryo...
The role of circRNA in reproduction is under investigation. CircRNAs are expressed in human testis, spermatozoa (SPZ), and seminal plasma. Their involvement in embryo development has also been suggested. Asthenozoospermia, a common cause of male infertility, is characterized by reduced or absent sperm motility in fresh ejaculate. While abnormal mitochondrial function, altered sperm tail, and genomic causes have been deeply investigated, the epigenetic signature of asthenozoospermic derived SPZ still remains unexplored. CircRNAs may take part in the repertoire of differentially expressed molecules in infertile men. Considering this background, we carried out a circRNA microarray, identifying a total of 9,138 transcripts, 22% of them novel based and 83.5% with an exonic structure. Using KEGG analysis, we evaluated the circRNA contribution in pathways related to mitochondrial function and sperm motility. In order to discriminate circRNAs with a differential expression in SPZ with differential morphological parameters, we separated sperm cells by Percoll gradient and analyzed their differential circRNA payload. A bioinformatic approach was then utilized to build a circRNA/miRNA/mRNA network. With the aim to demonstrate a dynamic contribution of circRNAs to the sperm epigenetic signature, we verified their modulation as a consequence of an oral amino acid supplementation, efficacious in improving SPZ motility.
Topics: Adult; Asthenozoospermia; Computational Biology; Gene Expression; Humans; Male; Microarray Analysis; RNA, Circular; Sperm Motility; Spermatozoa
PubMed: 32754116
DOI: 10.3389/fendo.2020.00395 -
Ecotoxicology and Environmental Safety May 2021Many endocrine disruptors may interfere with sperm motility, hyperactivation, and capacitation, thereby leading to male infertility. In the current study, we screened 14...
Many endocrine disruptors may interfere with sperm motility, hyperactivation, and capacitation, thereby leading to male infertility. In the current study, we screened 14 endocrine disruptors, including plant ingredients, cigarette ingredients, minerals, insecticides and fungicides, plastics, and plasticizers, to inhibit human sperm motility and forward motility. Only ziram, a dithiocarbamate fungicide, can effectively inhibit sperm motility, forward motility, hyperactivation, capacitation, and spontaneous acrosome reaction of normal human spermatozoa. Its half maximum inhibitory concentration (IC) values were less than 4 μM. Ziram also inhibited sperm motility and forward motility of asthenozoospermia spermatozoa and IC values were about 6-8 μM. In addition, ziram inhibited normal sperm motility, calcium influx, reactive oxygen species, and mitochondrial membrane potential at 2.5 and/or 5 μM, with IC values exceeding 100 μM, although it did not affect sperm DNA fragmentation up to 5 μM. Ziram-mediated inhibition of sperm motility and forward motility was irreversible. Forskolin, 8Br-cAMP, pentoxifylline, progesterone, vitamin E, and A23187 cannot prevent ziram-mediated inhibition of sperm motility and forward motility. Further studies have shown that ziram inhibited the level of tyrosine protein kinase with an IC value of about 10 μM, without affecting p21-activated kinase 4, and it caused damage to the mitochondrial structure of normal spermatozoa at 2.5 and 5 μM. In conclusion, ziram irreversibly inhibits human sperm motility, forward motility, and capacitation by reducing the level of tyrosine protein kinase and damaging the ultrastructure of mitochondria.
PubMed: 33984659
DOI: 10.1016/j.ecoenv.2021.112281 -
PloS One 2021The present study sought to investigate the common abnormalities and mtDNA mutations in the sperm of Ghanaian men attending the fertility Clinic at the Korle-Bu Teaching...
PURPOSE
The present study sought to investigate the common abnormalities and mtDNA mutations in the sperm of Ghanaian men attending the fertility Clinic at the Korle-Bu Teaching Hospital (KBTH). The study therefore provides a baseline data mtDNA mutations in a cross-section of Ghanaian men on referral to the fertility clinic at the KBTH.
MATERIALS AND METHODS
The semen of 55 men attending the fertility clinic were collected from the Urology and the Obstetrics and Gynaecology Departments of the KBTH. Demographic and clinical data were also collected using questionnaires. Semen analyses were performed and were followed by amplification and purification of mtDNA from total DNA extracted from the semen. Sequencing of the mtDNA amplicons was performed using the next generation sequencer (Illumina-MiSeq).
RESULTS
Asthenozoospermia, oligospermia and oligoasthenoteratozoospermia were observed in 1.79%, 5.36% and 28.57%, respectively, of the study participants. There was no association between drinking and/or smoking and history of gonorrhea infection on sperm status/morphology. A total of 785 point mutations were detected in the non-coding control regions, rRNA genes, tRNA genes and the coding regions of the mtDNA samples from the participants. Amongst these mutations, 16 transition mutations were predominantly detected in the mtDNA samples. Missense mutations that were present in only specific sperm abnormalities were identified and they may contribute to infertility in the study population.
CONCLUSION
The present study has identified various abnormal sperm phenotypes that are prevalent in the study population and provided a baseline data on mtDNA mutations in the spermatozoa of the patients. A wide range of sperm abnormalities were detected in the study population with no association with life style or history of gonorrhea infection. The mtDNA point mutations detected in the selected genes that were analysed were mostly transition mutations. These transition mutations might be critical for the development of abnormal sperm phenotypes underlying male infertility in the Ghanaian population.
Topics: Adult; Cross-Sectional Studies; DNA, Mitochondrial; Fertility Clinics; Ghana; High-Throughput Nucleotide Sequencing; Humans; Infertility, Male; Male; Middle Aged; Mitochondria; Mutation, Missense; Sequence Analysis, DNA; Spermatozoa; Young Adult
PubMed: 34129647
DOI: 10.1371/journal.pone.0252923