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European Review For Medical and... Jul 2022This study aimed at comparing sperm parameters and hormonal levels with L-carnitine vs. CoQ10 and Vitamin E therapy for patients with asthenozoospermia and... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study aimed at comparing sperm parameters and hormonal levels with L-carnitine vs. CoQ10 and Vitamin E therapy for patients with asthenozoospermia and teratozoospermia.
PATIENTS AND METHODS
A single-blind randomized controlled trial (RCT) was designed wherein patients were randomly allocated to receive L-carnitine complex nutrient treatment (study group - 15 g/bag, orally one bag at a time, twice a day) or CoQ10 (control group - 10 mg tablet orally, thrice daily) with Vitamin E (100 mg tablet orally, thrice daily) for three months. Outcome variables were sperm concentration, progressive sperm motility, normal sperm morphology, testosterone, follicle-stimulating hormone, luteinizing hormone (LH), and prolactin levels.
RESULTS
143 patients were analyzed (73 in study and 70 in control group). Compared to baseline, sperm count, progressive sperm motility, and morphology improved significantly in the study group, but only progressive sperm motility and morphology improved in the control group. Serum testosterone levels significantly increased both in the study and control groups, while LH increased only in the study but not in the control group. All sperm parameters showed significantly better improvement in the study group, compared to the control group. Testosterone and LH levels were also higher in the study group compared to the control group.
CONCLUSIONS
L-carnitine significantly improves sperm motility, morphology, and concentration, while also improving testosterone and LH levels. Use of CoQ10 and Vitamin E resulted in improvement of only sperm motility, morphology, and testosterone levels. L-carnitine was found to be superior to the combination of CoQ10 and Vitamin E in improving sperm parameters. Further studies examining clinical pregnancy rates are needed to strengthen the evidence.
Topics: Carnitine; Female; Humans; Infertility, Male; Luteinizing Hormone; Male; Pregnancy; Sperm Count; Sperm Motility; Spermatozoa; Testosterone; Ubiquinone; Vitamin E
PubMed: 35856361
DOI: 10.26355/eurrev_202207_29194 -
Journal of Assisted Reproduction and... Jan 2023Modeling methods for busulfan-induced oligoasthenozoospermia are controversial. We aimed to systematically review the modeling method of busulfan-induced oligospermia... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Modeling methods for busulfan-induced oligoasthenozoospermia are controversial. We aimed to systematically review the modeling method of busulfan-induced oligospermia and asthenozoospermia, and analyze changes in various evaluation indicators at different busulfan doses over time.
METHODS
We searched the Cochrane Library, PubMed databases, Web of Science, the Chinese National Knowledge Infrastructure, and the Chinese Biomedical Literature Service System until April 9, 2022. Animal experiments of busulfan-induced spermatogenesis dysfunction were included and screened. The model mortality and parameters of the evaluation indicators were subjected to meta-analysis.
RESULTS
Twenty-nine animal studies were included (control/model: 669/1829). The mortality of mice increased with busulfan dose. Significant spermatogenesis impairment occurred within 5 weeks, regardless of busulfan dose (10-40 mg/kg). Testicular weight (weighted mean difference [WMD]: - 0.04, 95% CI: - 0.05, - 0.03), testicular index (WMD: - 2.10, 95% CI: - 2.43, - 1.76), and Johnsen score (WMD: - 4.67, 95% CI: - 5.99, - 3.35) were significantly decreased. The pooled sperm counts of the model group were reduced by 32.8 × 10/ml (WMD: - 32.8, 95% CI: - 44.34, - 21.28), and sperm motility decreased by 37% (WMD: - 0.37, 95% CI: - 0.47, - 0.27). Sperm counts decreased slightly (WMD: - 3.03, 95% CI: - 3.42, - 2.64) in an intratesticular injection of low-dose busulfan (4 - 6 mg/kg), and the model almost returned to normal after one seminiferous cycle.
CONCLUSION
The model using low-dose busulfan (10 - 20 mg/kg) returned to normal after 10 - 15 weeks. However, in some spermatogenesis cycles, testicular weight reduction and testicular spermatogenic function damage were not proportional to busulfan dose. Sperm counts and motility results in different studies had significant heterogeneity. Standard protocols for sperm assessment in animal models were needed to reduce heterogeneity between studies.
Topics: Humans; Mice; Male; Animals; Oligospermia; Busulfan; Asthenozoospermia; Sperm Count; Sperm Motility; Semen
PubMed: 36508035
DOI: 10.1007/s10815-022-02674-y -
International Journal of Molecular... Apr 2022In mammals, sperm fertilization potential relies on efficient progression within the female genital tract to reach and fertilize the oocyte. This fundamental property is... (Review)
Review
In mammals, sperm fertilization potential relies on efficient progression within the female genital tract to reach and fertilize the oocyte. This fundamental property is supported by the flagellum, an evolutionarily conserved organelle that provides the mechanical force for sperm propulsion and motility. Importantly several functional maturation events that occur during the journey of the sperm cells through the genital tracts are necessary for the activation of flagellar beating and the acquisition of fertilization potential. Ion transporters and channels located at the surface of the sperm cells have been demonstrated to be involved in these processes, in particular, through the activation of downstream signaling pathways and the promotion of novel biochemical and electrophysiological properties in the sperm cells. We performed a systematic literature review to describe the currently known genetic alterations in humans that affect sperm ion transporters and channels and result in asthenozoospermia, a pathophysiological condition defined by reduced or absent sperm motility and observed in nearly 80% of infertile men. We also present the physiological relevance and functional mechanisms of additional ion channels identified in the mouse. Finally, considering the state-of-the art, we discuss future perspectives in terms of therapeutics of asthenozoospermia and male contraception.
Topics: Animals; Asthenozoospermia; Female; Humans; Ion Channels; Male; Mammals; Mice; Models, Animal; Sperm Motility; Spermatozoa
PubMed: 35409285
DOI: 10.3390/ijms23073926 -
Bioscience Reports Jul 2020Asthenozoospermia is one of the major causes of human male infertility. Long noncoding RNAs (lncRNAs) play critical roles in the spermatogenesis processes. The present... (Observational Study)
Observational Study
Asthenozoospermia is one of the major causes of human male infertility. Long noncoding RNAs (lncRNAs) play critical roles in the spermatogenesis processes. The present study aims to investigate the intricate regulatory network associated with asthenozoospermia. The lncRNAs expression profile was analyzed in the asthenozoospermia seminal plasma exosomes by RNA-sequencing, and the functions of differentially expressed genes (DEGs) were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and DO (Disease Ontology) enrichment analyses. Pearson's correlation test was utilized to calculate the correlation coefficients between lncRNA and mRNAs. Moreover, the lncRNA-miRNA-mRNA co-expression network was constructed with bioinformatics. From the co-expression analyses, we identified the cis regulated correlation pairs lncRNA-mRNA. To confirm sequencing results with five of the identified DElncRNAs were verified with quantitative reverse-transcription polymerase chain reaction (qRT-PCR). We identified 4228 significantly DEGs, 995 known DElncRNAs, 2338 DEmRNAs and 11,706 novel DElncRNAs between asthenozoospermia and normal group. GO and KEGG analyses showed that the DEGs were mainly associated with metabolism, transcription, ribosome and channel activity. We found 254,981 positive correlations lncRNA-mRNA pairs through correlation analysis. The detailed lncRNA-miRNA-mRNA regulatory network included 11 lncRNAs, 35 miRNAs and 59 mRNAs. From the co-expression analyses, we identified 7 cis-regulated correlation pairs lncRNA-mRNA. Additionally, the qRT-PCR analysis confirmed our sequencing results. Our study constructed the lncRNA-mRNA-miRNA regulation networks in asthenozoospermia. Therefore, the study findings provide a set of pivotal lncRNAs for future investigation into the molecular mechanisms of asthenozoospermia.
Topics: Adult; Asthenozoospermia; Case-Control Studies; Computational Biology; Exosomes; Gene Expression Profiling; Gene Regulatory Networks; Humans; Male; MicroRNAs; RNA, Long Noncoding; RNA, Messenger; Semen; Semen Analysis; Sequence Analysis, RNA
PubMed: 32614449
DOI: 10.1042/BSR20194041 -
Scientific Reports Feb 2023Asthenozoospermia (AZS) is a severe form of male infertility with no clear pathogenesis, despite numerous research efforts, there is no consensus on this. This study was...
Asthenozoospermia (AZS) is a severe form of male infertility with no clear pathogenesis, despite numerous research efforts, there is no consensus on this. This study was to investigate the expression of gene-associated with retinoid-interferon-induced mortality 19 (GRIM-19) in the sperm of patients with asthenozoospermia and the regulation of GC-2 spd cell proliferation, apoptosis and migration. We analyzed the sperm samples from 82 asthenozoospermia and normal patients were collected in the First People's Hospital of Shangqiu and the First Affiliated Hospital of Zhengzhou University. Immunofluorescence, western blots and RT-qPCR analyses were used to verify the expressions of GRIM-19. MTT assays were used to assess cell proliferations, flow cytometry was performed to assess cell apoptosis, wound‑healing was performed to measure cell migration. Immunofluorescence showed that GRIM-19 is predominantly expressed in the sperm mid-piece, the mRNA expressions of GRIM-19 in sperms of the asthenozoospermia group were significantly low, relative to the normal group (OR 0.266; 95% CI = 0.081-0.868; P = 0.028). The protein expressions of GRIM-19 in sperms of the asthenozoospermia group were significantly lower than that of the normal group as well (GRIM-19/GAPDH: 0.827 ± 0.063 vs 0.458 ± 0.033; P < 0.001). GRIM-19 overexpression promotes GC-2 spd cell proliferation and migration and reduces apoptosis, while GRIM-19-silenced reduces GC-2 spd cell proliferation and migration and increased apoptosis. GRIM-19 is closely related to the occurrence of asthenozoospermia and promotes GC-2 spd cell proliferation and migration and reduces apoptosis.
Topics: Humans; Male; Asthenozoospermia; Semen; Apoptosis; Apoptosis Regulatory Proteins; Cell Proliferation
PubMed: 36813832
DOI: 10.1038/s41598-023-29775-7 -
Medicine Apr 2021According to the World Health Organization, the global incidence of infertility is about 15%, and more than 50% of infertility cases are caused by male infertility....
BACKGROUND
According to the World Health Organization, the global incidence of infertility is about 15%, and more than 50% of infertility cases are caused by male infertility. Asthenozoospermia is caused by male fertility decline and male infertility. Due to work pressure, environmental pollution, sexual diseases, and other factors, the number of patients with asthenozoospermia has increased in recent years. It has been confirmed that acupuncture has a certain effect on patients with asthenozoospermia. Acupuncture and moxibustion can be an adjuvant treatment plan for the treatment of asthenozoospermia in addition to drug treatment.
METHODS
Randomized controlled trials of acupuncture for asthenozoospermia will be searched in the relevant database, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), and Chinese Scientific Journal Database (VIP database). The studies of electronic searches will be exported to EndNote V.9.1 software. We will run meta-analyses using the Review Manager (RevMan) V.5.3 software. Any disagreements will be solved in consultation with a third reviewer.
RESULTS
Our study aims to explore the efficacy of acupuncture for asthenozoospermia and to provide up-to-date evidence for clinical of asthenozoospermia.
CONCLUSION
This study will perform a comprehensive systematic review and meta-analysis on the efficacy of acupuncture for asthenozoospermia, making up for the lack of relevant evidence of the clinical use of acupuncture.
INPLASY REGISTRATION NUMBER
INPLASY 202140032.
Topics: Acupuncture Therapy; Asthenozoospermia; Humans; Male; Meta-Analysis as Topic; Moxibustion; Research Design; Systematic Reviews as Topic; Treatment Outcome
PubMed: 33907155
DOI: 10.1097/MD.0000000000025711 -
Journal of Lasers in Medical Sciences 2022About 50% of infertility problems are related to male factors and reduced sperm motility. The important factor that affects the structure and function of sperm is... (Review)
Review
About 50% of infertility problems are related to male factors and reduced sperm motility. The important factor that affects the structure and function of sperm is reactive oxygen species (ROS), and over-concentration of ROS reduces the quality and motility of sperm. Photobiomodulation therapy (PBMT) using red to near-infrared (NIR) light is useful in oxidative stress restoration. It plays a therapeutic role in disorders such as asthenospermia, oligospermia cases, and cryopreserved sperm. It also enhances the metabolic capacity of sperm and increases the low-level and non-harmful intracellular content of Ca, nitric oxide (NO), and ROS in the stressed cells. Likewise, it modulates survival intracellular pathways and maintains the motility, viability, DNA, and acrosome integrity of sperm. This article reviews the state-of-the-art preclinical and clinical evidence regarding the efficacy of semen PBMT.
PubMed: 37041786
DOI: 10.34172/jlms.2022.75 -
Human Reproduction (Oxford, England) Aug 2021What are the causative genetic variants in patients with male infertility due to severe sperm motility disorders?
STUDY QUESTION
What are the causative genetic variants in patients with male infertility due to severe sperm motility disorders?
SUMMARY ANSWER
We identified high confidence disease-causing variants in multiple genes previously associated with severe sperm motility disorders in 10 out of 21 patients (48%) and variants in novel candidate genes in seven additional patients (33%).
WHAT IS KNOWN ALREADY
Severe sperm motility disorders are a form of male infertility characterised by immotile sperm often in combination with a spectrum of structural abnormalities of the sperm flagellum that do not affect viability. Currently, depending on the clinical sub-categorisation, up to 50% of causality in patients with severe sperm motility disorders can be explained by pathogenic variants in at least 22 genes.
STUDY DESIGN, SIZE, DURATION
We performed exome sequencing in 21 patients with severe sperm motility disorders from two different clinics.
PARTICIPANTS/MATERIALS, SETTING, METHOD
Two groups of infertile men, one from Argentina (n = 9) and one from Australia (n = 12), with clinically defined severe sperm motility disorders (motility <5%) and normal morphology values of 0-4%, were included. All patients in the Argentine cohort were diagnosed with DFS-MMAF, based on light and transmission electron microscopy. Sperm ultrastructural information was not available for the Australian cohort. Exome sequencing was performed in all 21 patients and variants with an allele frequency of <1% in the gnomAD population were prioritised and interpreted.
MAIN RESULTS AND ROLE OF CHANCE
In 10 of 21 patients (48%), we identified pathogenic variants in known sperm assembly genes: CFAP43 (3 patients); CFAP44 (2 patients), CFAP58 (1 patient), QRICH2 (2 patients), DNAH1 (1 patient) and DNAH6 (1 patient). The diagnostic rate did not differ markedly between the Argentinian and the Australian cohort (55% and 42%, respectively). Furthermore, we identified patients with variants in the novel human candidate sperm motility genes: DNAH12, DRC1, MDC1, PACRG, SSPL2C and TPTE2. One patient presented with variants in four candidate genes and it remains unclear which variants were responsible for the severe sperm motility defect in this patient.
LARGE SCALE DATA
N/A.
LIMITATIONS, REASONS FOR CAUTION
In this study, we described patients with either a homozygous or two heterozygous candidate pathogenic variants in genes linked to sperm motility disorders. Due to unavailability of parental DNA, we have not assessed the frequency of de novo or maternally inherited dominant variants and could not determine the parental origin of the mutations to establish in all cases that the mutations are present on both alleles.
WIDER IMPLICATIONS OF THE FINDINGS
Our results confirm the likely causal role of variants in six known genes for sperm motility and we demonstrate that exome sequencing is an effective method to diagnose patients with severe sperm motility disorders (10/21 diagnosed; 48%). Furthermore, our analysis revealed six novel candidate genes for severe sperm motility disorders. Genome-wide sequencing of additional patient cohorts and re-analysis of exome data of currently unsolved cases may reveal additional variants in these novel candidate genes.
STUDY FUNDING/COMPETING INTEREST(S)
This project was supported in part by funding from the Australian National Health and Medical Research Council (APP1120356) to M.K.O.B., J.A.V. and R.I.M.L., The Netherlands Organisation for Scientific Research (918-15-667) to J.A.V., the Royal Society and Wolfson Foundation (WM160091) to J.A.V., as well as an Investigator Award in Science from the Wellcome Trust (209451) to J.A.V. and Grants from the National Research Council of Argentina (PIP 0900 and 4584) and ANPCyT (PICT 9591) to H.E.C. and a UUKi Rutherford Fund Fellowship awarded to B.J.H.
Topics: Australia; Exome; Humans; Infertility, Male; Male; Sperm Motility; Sperm Tail; Spermatozoa; Exome Sequencing
PubMed: 34089056
DOI: 10.1093/humrep/deab099 -
Frontiers in Cell and Developmental... 2020With the continued steep rise of the global human population, and the paucity of safe and practical contraceptive options available to men, the need for development of... (Review)
Review
With the continued steep rise of the global human population, and the paucity of safe and practical contraceptive options available to men, the need for development of effective and reversible non-hormonal methods of male fertility control is widely recognized. Currently there are several contraceptive options available to men, however, none of the non-hormonal alternatives have been clinically approved. To advance progress in the development of a safe and reversible contraceptive for men, further identification of novel reproductive tract-specific druggable protein targets is required. Here we provide an overview of genes/proteins identified in the last decade as specific or highly expressed in the male reproductive tract, with deletion phenotypes leading to complete male infertility in mice. These phenotypes include arrest of spermatogenesis and/or spermiogenesis, abnormal spermiation, abnormal spermatid morphology, abnormal sperm motility, azoospermia, globozoospermia, asthenozoospermia, and/or teratozoospermia, which are all desirable outcomes for a novel male contraceptive. We also consider other associated deletion phenotypes that could impact the desirability of a potential contraceptive. We further discuss novel contraceptive targets underscoring promising leads with the objective of presenting data for potential druggability and whether collateral effects may exist from paralogs with close sequence similarity.
PubMed: 32161754
DOI: 10.3389/fcell.2020.00061 -
Theranostics 2021Idiopathic asthenozoospermia (iAZS) is one of the major causes of male infertility and has no effective therapeutic treatment. Understanding the potential mechanisms...
Idiopathic asthenozoospermia (iAZS) is one of the major causes of male infertility and has no effective therapeutic treatment. Understanding the potential mechanisms that cause it may be helpful in seeking novel targets and treatment strategies for overcoming the problem of low sperm motility in iAZS individuals. Computer-assisted semen analysis (CASA) was utilized to assess the sperm motility. RT-qPCR, Western blot, immunofluorescence staining, and calcium imaging analysis were performed to examine the expression and function of CatSper channels. Hyperactivation and acrosome reaction were used to evaluate the functional characteristics of epididymal sperm. fertility assay was applied to determine the fertility of rats. CatSper1 knockdown and overexpression experiments were performed to confirm the roles of CatSper channels in the pathogenesis of iAZS and the therapeutic effects of electroacupuncture (EA) treatment on AZS model rats. Here, we reported a functional down-regulation of CatSper channel from CatSper1 to CatSper 4 in the sperm of both iAZS patients and ornidazole (ORN)-induced AZS model rats, and an impaired sperm function characterized by a reduction of protein tyrosine phosphorylation, hyperactivation, and acrosome reaction in the epididymal sperm of AZS rats. Knockdown of CatSper1 in the testis tissues is sufficient to induce AZS in normal rats, and this action was validated by the reversal effects of CatSper1 overexpression. Transcutaneous electrical acupoint stimulation (TEAS) and electroacupuncture (EA) at 2 Hz frequency improve the sperm motility via enhancing the functional expression of CatSper channels in the sperm. Gene silencing in the sperm abolishes the therapeutic effects of 2 Hz-EA treatment on AZS rats. We conclude that a functional down-regulation of CatSper channel in the sperm may be a contributor or a downstream indicator for a portion of AZS, especially iAZS, while 2 Hz-TEAS or EA treatment has a therapeutic effect on iAZS through inducing the functional up-regulation of CatSper channels in the sperm. This study provides a novel mechanism for the pathogenesis of some AZS especially iAZS, and presents a potential therapeutic target of CatSper for iAZS treatment. Acupuncture treatment like TEAS may be used as a promising complementary and alternative medicine (CAM) therapy for male infertility caused by iAZS in clinical practice.
Topics: Acrosome Reaction; Acupuncture Therapy; Adult; Animals; Asthenozoospermia; Calcium Channels; Down-Regulation; Humans; Male; Middle Aged; Rats; Sperm Motility; Spermatozoa; Young Adult
PubMed: 33456575
DOI: 10.7150/thno.51869