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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 -
Clinica Chimica Acta; International... Aug 2023Asthenozoospermia (AZS) is a disease characterized by decreased sperm motility induced by multiple etiologies, and the pathological mechanisms of various AZS are...
BACKGROUND
Asthenozoospermia (AZS) is a disease characterized by decreased sperm motility induced by multiple etiologies, and the pathological mechanisms of various AZS are unclear. We simultaneously analyzed the metabolic profiling of four representative AZS to provide new insights into the etiologies of AZS.
METHOD
Seminal plasma samples were collected from healthy control (HC; n = 30) and four AZS induced by varicocele (VA, n = 30), obesity (OA, n = 22), reproductive system infections (RA; n = 17) and idiopathic (IA, n = 30), respectively, and were analyzed using gas chromatography-mass spectrometry. Disturbed metabolites and metabolic pathways were compared between AZS and HC, as well as IA and the other three AZS.
RESULTS
A total of 40 different metabolites were identified in the seminal plasma of AZS and HC, of which lactic acid, fructose, citric acid, glutamine and pyruvic acid metabolic abnormalities associated with all the AZS groups, while each AZS group had unique metabolic changes. RA was significantly separated from the other three AZS, and metabolites such as cholesterol, octadecanoic acid and serine mainly contributed to the separation.
CONCLUSION
The comprehensive metabolomic analysis and comparison of four various AZS provided evidence and clues for the mechanism mining, which will benefit future etiology, diagnosis and treatment of AZS.
Topics: Humans; Male; Semen; Asthenozoospermia; Sperm Motility; Metabolomics; Citric Acid
PubMed: 37652159
DOI: 10.1016/j.cca.2023.117530 -
Biology of Reproduction Apr 2019Increasing studies have shown that specific mRNAs and miRNAs expressed in mature sperm may be related to sperm motility. However, the expression profiles and roles of...
Increasing studies have shown that specific mRNAs and miRNAs expressed in mature sperm may be related to sperm motility. However, the expression profiles and roles of lncRNAs in sperm remain unknown. In the present study, numerous lncRNAs were identified in human sperm, and some lncRNAs were expressed exclusively in sperm and testis. Compared with those in normal sperm, the lncRNA expression profiles in asthenozoospermia (AZS) sperm showed significant differences. Gene ontology and pathway analyses showed that function of differentially expressed lncRNA targets and mRNAs between AZS and normal sperm were closely linked with many processes involved in spermatogenesis and sperm function. Furthermore, among the upregulated lncRNAs in AZS sperm, lnc32058, lnc09522, and lnc98487, which exhibited specific/enriched sperm and testicular expression, increased simultaneously in the same AZS sperm samples, and their expression levels were correlated with sperm progressive motility. This is the first systematic study of lncRNA expression profiles in human mature sperm indicating an association between lncRNA expression and sperm motility. The study provides a preliminary database for identifying lncRNAs crucial for human spermatogenesis and sperm function, and new insights into our understanding of the regulation of sperm motility and causes of male infertility.
Topics: Asthenozoospermia; Cells, Cultured; Gene Expression Profiling; Humans; Infertility, Male; Male; RNA, Long Noncoding; Semen Analysis; Spermatogenesis; Spermatozoa; Transcriptome
PubMed: 30517597
DOI: 10.1093/biolre/ioy253 -
Annals of Human Genetics May 2020Multiple morphological abnormalities of the sperm flagella (MMAF) is one kind of severe asthenozoospermia, which is caused by dysplastic development of sperm flagella....
BACKGROUND
Multiple morphological abnormalities of the sperm flagella (MMAF) is one kind of severe asthenozoospermia, which is caused by dysplastic development of sperm flagella. In our study, we sought to investigate the novel gene mutations leading to severe asthenozoospermia and MMAF.
METHODS AND MATERIALS
The patient's spermatozoa were tested by Papanicolaou staining and transmission electron microscopy. Whole exome sequencing was performed on the patient with severe asthenozoospermia and MMAF. Sanger sequencing verified the mutations in the family. The expression of DNAH17 was detected by immunofluorescence and Western blot.
RESULTS
Spermatozoa sample from the patient showed severe asthenozoospermia and MMAF. We detected biallelic mutations (c.C4445T, p.A1482V and c.C6857T, and p.S2286L) in DNAH17 (MIM:610063). The protein expression of DNAH17 was almost undetectable in spermatozoa from the patient with the biallelic mutations.
CONCLUSION
These results demonstrated that DNAH17 may be involved in severe asthenozoospermia and MMAF.
Topics: Adult; Alleles; Amino Acid Sequence; Asthenozoospermia; Axonemal Dyneins; DNA Mutational Analysis; Genes, Recessive; Humans; Male; Pedigree; Sperm Tail; Spermatozoa; Exome Sequencing
PubMed: 31841227
DOI: 10.1111/ahg.12369 -
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 -
Andrology Mar 2024Although antioxidants are largely used in subfertile men with oligo-astheno-teratozoospermia (OAT), the choice among different molecules is challenged by the lack of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although antioxidants are largely used in subfertile men with oligo-astheno-teratozoospermia (OAT), the choice among different molecules is challenged by the lack of comparative head-to-head studies. The network meta-analysis (NMA) can overcome limitations of pairwise meta-analyses, since it incorporates direct and indirect evidence into a single model generating an effectiveness hierarchy.
OBJECTIVE
To assess with a NMA the effects of antioxidants in improving seminal parameters in idiopathic OAT.
MATERIALS AND METHODS
PubMed, Scopus, Cinahl, and Cochrane Library databases were searched for randomized controlled trials (RCTs) comparing any antioxidant treatment to each other or placebo in men with at least one idiopathic seminal abnormality. Data were included in a random-effects NMA, where efficacy of treatments was ranked by surface under the cumulative ranking curve (SUCRA).
RESULTS
29 RCTs provided information on 2045 men (mean age: 33.5 years) with idiopathic OAT and 19 antioxidant preparations. Compared to placebo, l-carnitine, especially in combination with l-acetyl-carnitine (LAC), had the highest SUCRA for sperm concentration, progressive motility, and morphology. Folate was the only other compound effective on sperm concentration. Vitamin E+selenium or zinc had the highest SUCRA for total motility. A contribution on progressive motility was revealed for pentoxifylline and vitamin E+CoQ10.
Topics: Male; Humans; Adult; Antioxidants; Semen; Network Meta-Analysis; Spermatozoa; Asthenozoospermia; Vitamin E; Sperm Motility
PubMed: 37495550
DOI: 10.1111/andr.13498 -
Reproduction & Fertility Apr 2022Sperm motility varies between ejaculates from different men and from individual men. We studied normozoospermic and asthenozoospermic ejaculates after density-gradient...
UNLABELLED
Sperm motility varies between ejaculates from different men and from individual men. We studied normozoospermic and asthenozoospermic ejaculates after density-gradient centrifugation washing (DCG, 80/40%) and compared high- (80%) and low (40%)-motility sperm populations within the same sample. Our objective was to identify differences in endogenous metabolomes and energy metabolism in relation to sperm motility. H-Nuclear Magnetic Resonance spectroscopy (NMR) measured the endogenous metabolome of live human sperm. Incubating sperm with C-labelled substrates detected energy metabolism by C-NMR. The study examined 850 ejaculates and diagnosed asthenozoospermia in 6.1%. DGC was used to wash 160 normozoospermic (N) and 52 asthenozoospermic (A) ejaculates to recover high-motility sperm from the pellet (80N/80A) and low motility from the interface (40N/40A). H-NMR spectra, 45(N) and 15(A), were binned and the integrals normalised by sperm concentration. Sperm from 126(N) and 36(A) ejaculates were incubated with either C-glucose, C-fructose or C-pyruvate. C-NMR lactate and bicarbonate integrals were normalised by motile or vital sperm concentrations. H-NMR spectra choline integrals from the 80A population were significantly lower than the 80N, < 0.0001. C-substrate conversion to lactate was significantly higher for 40A sperm than 80A sperm when normalised by motile sperm concentration. Bicarbonate integrals were sporadically observed. Sperm from asthenozoospermic ejaculates had similar glycolytic requirements to normozoospermic ones, with larger differences observed between 40 and 80% sperm populations. Higher lactate levels produced by 40% sperm may indicate that impaired sperm motility is due to dysregulated energy metabolism. The alteration in choline metabolism provides opportunities to understand the aetiology of asthenozoospermia.
LAY SUMMARY
How well sperm swim (motility) varies between ejaculates from different men? Normal sperm motility is beneficial to conception and some men diagnosed with infertility have low sperm motility. Sperm metabolise molecules to produce the energy required for motility. We measured concentrations of molecules within sperm and metabolism of molecules given to sperm and related these to the proportion of motile sperm. The study examined 850 sperm samples and found low motility in 6.1%. Metabolism of molecules given to sperm was similar between low and normal motility sperm samples. However, when the most motile sperm were separated from the rest, they were more efficient in metabolising these molecules to achieve motility. Lower concentrations of a molecule called choline were found in low-motility sperm samples compared to normal samples. Choline is associated with cell membranes, energy metabolism and oxidative stress, which may give opportunities to understand the causes of low motility.
Topics: Asthenozoospermia; Bicarbonates; Choline; Humans; Lactates; Magnetic Resonance Spectroscopy; Male; Semen; Sperm Motility; Spermatozoa
PubMed: 35514541
DOI: 10.1530/RAF-21-0101 -
Asian Journal of Andrology 2022Large numbers of microbes can be present in seminal fluid, and there are differences in the semen microbiota between normal and abnormal semen samples. To evaluate the...
Large numbers of microbes can be present in seminal fluid, and there are differences in the semen microbiota between normal and abnormal semen samples. To evaluate the semen microbiota in patients with leukocytospermia, 87 seminal fluid samples, including 33 samples with a normal seminal leukocyte count and 54 samples with leukocytospermia, were obtained for a cross-sectional analysis. Twenty samples with a normal seminal leukocyte count had normal sperm parameters (Control group), and 13 samples with a normal seminal leukocyte count were from asthenozoospermia patients (Ast group). However, 32 samples with leukocytospermia were from asthenozoospermia patients (LA group), and only 22 samples with leukocytospermia had normal sperm parameters (Leu group). The 16S ribosomal RNA (rRNA) gene sequencing method was used to sequence the microbiota in the seminal fluid, and multiple bioinformatics methods were utilized to analyze the data. Finally, the results showed that the worse sperm parameters were observed in the leukocytospermia-related groups. Semen microbiota analysis found that there was increased alpha diversity in the leukocytospermia-related groups. Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes were the primary phyla in the seminal fluid. Two microbiota profiles, namely, Lactobacillus-enriched and Streptococcus-enriched groups, were identified in this study. The majority of the samples in the groups with a normal seminal leukocyte count could be categorized as Lactobacillus-enriched, whereas the majority of the leukocytospermia samples could be categorized as Streptococcus-enriched. Our study indicated that males with leukocytospermia have worse sperm parameters and a different semen microbiota composition compared to males with a normal seminal leukocyte count.
Topics: Asthenozoospermia; Cross-Sectional Studies; Humans; Infertility, Male; Male; Microbiota; Semen; Spermatozoa
PubMed: 34916474
DOI: 10.4103/aja202172 -
Experimental and Molecular Pathology Dec 2020Long non-coding RNAs (lncRNAs) have a particular expression in the testicular tissue and exhibit a regulatory function on the reproduction system. ANO1-AS2 (linc02584),...
Long non-coding RNAs (lncRNAs) have a particular expression in the testicular tissue and exhibit a regulatory function on the reproduction system. ANO1-AS2 (linc02584), as an lncRNA is located near the anoctamin1 (ANO1) gene. ANO1 is an important component of the transmembrane system exhibiting expression modifications in the idiopathic infertile men. Therefore, the present study was conducted to investigate the relationship between ANO1-AS2 and ANO1 gene expression with sperm motility and morphology in the patients with asthenozoospermia (AZ) and terato- asthenozoospermia (TAZ). The study population included 32 patients with AZ, 35 patients with TAZ, and 34 people with normozoospermia (NZ, control). The expression levels of ANO1 gene and ANO1-AS2 in the spermatozoa were measured by the quantitative real-time polymerase chain reaction (PCR). Docking analysis was performed to investigate the interactions of the ANO1 gene promoter and intermediate elements with ANO1-AS2. ANO1 gene expression was significantly (P < 0.05) downregulated in the patients however; ANO1-AS2 expression was significantly upregulated (P < 0.05). The subsequent analysis confirmed the inverse correlation between ANO1 and ANO1-AS2. ANO1 gene expression level was significantly positively correlated with sperm motility and morphology (P < 0.05). Moreover, ANO1-AS2 expression showed an inverse correlation with sperm motility and morphology (P < 0.05). Docking analysis confirmed that ANO1-AS2 could stably interact with ANO1 gene promoter. In conclusion, ANO1-AS2 is likely to downregulate the ANO1 gene by interacting with ANO1 gene promoter, which can influence the sperm motility and morphology.
Topics: Adult; Anoctamin-1; Asthenozoospermia; Gene Expression Regulation, Developmental; Humans; Infertility, Male; Male; Neoplasm Proteins; RNA, Long Noncoding; Sperm Motility; Spermatozoa
PubMed: 32916161
DOI: 10.1016/j.yexmp.2020.104528 -
Andrologia Apr 2017The association of dietary nutrient patterns and sperm motility is not yet well elucidated, and previous studies have just focused on the isolated nutrients. This...
The association of dietary nutrient patterns and sperm motility is not yet well elucidated, and previous studies have just focused on the isolated nutrients. This case-control study examined the association of nutrient patterns with asthenozoospermia among Iranian men. In total, 107 incident asthenozoospermic men and 235 age-matched controls were interviewed through the infertility clinics in Tehran, Iran, from January 2012 to November 2013. Semen quality data were analysed according to the fifth edition of WHO guideline. Nutrient patterns were identified using principal component analysis based on semiquantitative 168-item food frequency questionnaires. All nutrient intakes were energy-adjusted by the residual method. In principal component analysis, three dietary patterns emerged. The first pattern, which was high in vitamin E, vitamin D, vitamin C, zinc, folate, total fibre, selenium and polyunsaturated fatty acids, was significantly associated with lower risk of asthenozoospermia. After adjustment for potential confounders, participants in the highest tertile of the first pattern scores had 51% lower risk of asthenozoospermia compared with those in the lowest (p-trend: .004). Our findings suggest that adherence to the pattern comprising mainly of antioxidant nutrients may be inversely associated with asthenozoospermia.
Topics: Adult; Antioxidants; Asthenozoospermia; Case-Control Studies; Diet; Food; Humans; Iran; Male; Risk; Sperm Motility; Surveys and Questionnaires; Young Adult
PubMed: 27246740
DOI: 10.1111/and.12624