-
Genes Feb 2023Infertility is a major health problem worldwide without an effective therapy or cure. It is estimated to affect 8-12% of couples in the reproductive age group, equally... (Review)
Review
Infertility is a major health problem worldwide without an effective therapy or cure. It is estimated to affect 8-12% of couples in the reproductive age group, equally affecting both genders. There is no single cause of infertility, and its knowledge is still far from complete, with about 30% of infertile couples having no cause identified (named idiopathic infertility). Among male causes of infertility, asthenozoospermia (i.e., reduced sperm motility) is one of the most observed, being estimated that more than 20% of infertile men have this condition. In recent years, many researchers have focused on possible factors leading to asthenozoospermia, revealing the existence of many cellular and molecular players. So far, more than 4000 genes are thought to be involved in sperm production and as regulators of different aspects of sperm development, maturation, and function, and all can potentially cause male infertility if mutated. In this review, we aim to give a brief overview of the typical sperm flagellum morphology and compile some of the most relevant information regarding the genetic factors involved in male infertility, with a focus on sperm immotility and on genes related to sperm flagellum development, structure, or function.
Topics: Male; Humans; Female; Sperm Tail; Asthenozoospermia; Semen; Sperm Motility; Infertility, Male
PubMed: 36833310
DOI: 10.3390/genes14020383 -
Zhonghua Nan Ke Xue = National Journal... Jan 2015To evaluate the effect and safety of L-carnitine in the treatment of idiopathic oligoasthenozoospermia based on current clinical evidence. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the effect and safety of L-carnitine in the treatment of idiopathic oligoasthenozoospermia based on current clinical evidence.
METHODS
We searched the Cochrane Library, PubMed, MEDLINE, EMBASE, CNKI, VIP, CBM and Wanfang Database from the establishment to April 2014 for the published literature on the treatment of idiopathic oligoasthenozoospermia with L-carnitine. We conducted literature screening, data extraction, and assessment of the methodological quality of the included trials according to the inclusion and exclusion criteria, followed by statistical analysis with the RevMan 5. 2 software.
RESULTS
Seven randomized controlled trials involving 751 patients with idiopathic oligoasthenozoospermia met the inclusion criteria, and 678 of them were included in the meta-analysis. L-carnitine treatment achieved a significantly increased rate of spontaneous pregnancy as compared with the control group (RR = 3.2, 95% CI 1.74 to 5.87, P = 0.0002). After 12-16 and 24-26 weeks of medication, total sperm motility (WMD = 5.21, 95% CI 2.78 to 7.64, P < 0.0001 and WMD = 9.29, 95% CI 1.28 to 17.29, P = 0.02) and the percentage of progressively motile sperm (WMD = 12.44, 95% CI 4.58 to 20.31, P = 0.002 and WMD = 9.76, 95% CI 3.56 to 15.97, P = 0.002) were remarkably higher than those in the control group, but no statistically significant differences were observed in sperm concentration between the two groups (WMD = 4.91, 95% CI -2.63 to 12.45, P = 0.2 and WMD = 0.93, 95% CI -3.48 to 5.34, P = 0.68). After 12-16 weeks of treatment, the percentage of morphologically abnormal sperm was markedly decreased in the L-carnitine group as compared with the control (WMD = -2.48, 95% CI -4.35 to -0.61, P = 0.009), but showed no significant difference from the latter group after 24-26 weeks (WMD = -4.38, 95% CI -9.66 to 0.89, P = 0.1). No statistically significant difference was found in the semen volume between the two groups after 12-16 or 24-26 weeks of medication (WMD = -0.13, 95% CI -0.43 to 0.18, P = 0.42 and WMD = 0.28, 95% CI -0.02 to 0.58, P = 0.07). No serious L-carnitine-related adverse events were reported in 4 of the randomniized controlled trials.
CONCLUSION
The current evidence indicates that L-carnitine can improve spontaneous pregnancy and semen parameters in the treatment of idiopathic oligoasthenozoospermia, with no serious adverse reactions.
Topics: Female; Humans; Male; Pregnancy; Asthenozoospermia; Carnitine; Pregnancy Rate; Randomized Controlled Trials as Topic; Semen Analysis; Sperm Count; Sperm Motility
PubMed: 25707144
DOI: No ID Found -
Andrologia Aug 2022Motility and morphology are two important characteristics of a fertile spermatozoon. CFAP44 gene encodes flagellar protein 44 involved in the formation and function of...
Motility and morphology are two important characteristics of a fertile spermatozoon. CFAP44 gene encodes flagellar protein 44 involved in the formation and function of the flagella and cilia. Long non-coding RNAs are regulatory elements involved in several processes, including reproduction. We aimed to study the alterations in the expressions of CFAP44 and CFAP44-AS1 genes in infertile men with asthenozoospermia and terato-asthenozoospermia. In this case-control study, a total of 105 subjects, including 35 TAZ patients, 34 AZ patients and 35 normozoospermic men, were enrolled. After RNA extraction from spermatozoa samples, quantitative real-time PCR was performed to compare the expression of CFAP44 and CFAP44-AS1 between the studied groups. A meaningful reduction in CFAP44 expression and a significant reduction in the expression of CFAP44-AS1 were observed. Moreover, a positive correlation between both genes' expressions and normal sperm morphology was detected in NZ, AZ and TAZ groups. Also, there was a positive relation between CFAP44 gene expression and sperm motility in AZ and TAZ groups. The expression of CFAP44-AS1 was positively correlated with sperm motility and morphology. Present results confirm the role of CFAP44 and CFAP44-AS1 in the motility and morphology of spermatozoon, and deregulation of these genes may contribute to male infertility.
Topics: Asthenozoospermia; Case-Control Studies; Humans; Male; Semen; Sperm Motility; Spermatozoa
PubMed: 35470451
DOI: 10.1111/and.14447 -
Advanced Science (Weinheim,... Apr 2022Sperm motility is a significant predictor of male fertility potential and is directly linked to fertilization success in both natural and some forms of assisted...
Sperm motility is a significant predictor of male fertility potential and is directly linked to fertilization success in both natural and some forms of assisted reproduction. Sperm motility can be impaired by both genetic and environmental factors, with asthenozoospermia being a common clinical presentation. Moreover, in the setting of assisted reproductive technology clinics, there is a distinct absence of effective and noninvasive technology to increase sperm motility without detriment to the sperm cells. Here, a new method is presented to boost sperm motility by increasing the intracellular rate of metabolic activity using high frequency ultrasound. An increase of 34% in curvilinear velocity (VCL), 10% in linearity, and 32% in the number of motile sperm cells is shown by rendering immotile sperm motile, after just 20 s exposure. A similar effect with an increase of 15% in VCL treating human sperm with the same setting is also identified. This cell level mechanotherapy approach causes no significant change in cell viability or DNA fragmentation index, and, as such, has the potential to be applied to encourage natural fertilization or less invasive treatment choices such as in vitro fertilization rather than intracytoplasmic injection.
Topics: Animals; Asthenozoospermia; Cattle; Fertilization in Vitro; Humans; Infertility, Male; Male; Sperm Motility; Spermatozoa
PubMed: 35419997
DOI: 10.1002/advs.202104362 -
Frontiers in Endocrinology 2023Asthenoteratozoospermia is one of the most common causes of male infertility. Several genes have been identified as genetic causative factors, but there is a...
INTRODUCTION
Asthenoteratozoospermia is one of the most common causes of male infertility. Several genes have been identified as genetic causative factors, but there is a considerable genetic heterogeneity underlying asthenoteratozoospermia. In this study, we performed a genetic analysis of two brothers from a consanguineous Uighur family in China to identify gene mutations causative for asthenoteratozoospermia-related male infertility.
METHODS
Two related patients with asthenoteratozoospermia from a large consanguineous family were sequenced by whole-exome sequencing and Sanger sequencing to identify disease-causing genes. Scanning and transmission electron microscopy analysis revealed ultrastructural abnormalities of spermatozoa. Quantitative real-time PCR (qRT-PCR) analysis and immunofluorescence (IF) analysis were used to assess the expression of the mutant messenger RNA (mRNA) and protein.
RESULTS
A novel homozygous frameshift mutation (c.2823dupT, p.Val942Cysfs*21) in was identified in both affected individuals and was predicted to be pathogenic. Papanicolaou staining and electron microscopy revealed multiple morphological and ultrastructural abnormalities of affected spermatozoa. qRT-PCR and IF analysis showed abnormal expression of DNAH6 in affected sperm, probably due to premature termination code and decay of abnormal 3' untranslated region (UTR) region of mRNA. Furthermore, intracytoplasmic sperm injection could achieve successful fertilization in infertile men with mutations.
DISCUSSION
The novel frameshift mutation identified in DNAH6 may contribute to asthenoteratozoospermia. These findings expand the spectrum of genetic mutations and phenotypes associated with asthenoteratozoospermia and may be useful for genetic and reproductive counseling in male infertility.
Topics: Humans; Male; Asthenozoospermia; Frameshift Mutation; Infertility, Male; RNA, Messenger; Semen; Sperm Tail; Dyneins
PubMed: 37424858
DOI: 10.3389/fendo.2023.1122004 -
American Journal of Human Genetics Mar 2023Primate-specific genes (PSGs) tend to be expressed in the brain and testis. This phenomenon is consistent with brain evolution in primates but is seemingly contradictory...
Primate-specific genes (PSGs) tend to be expressed in the brain and testis. This phenomenon is consistent with brain evolution in primates but is seemingly contradictory to the similarity of spermatogenesis among mammals. Here, using whole-exome sequencing, we identified deleterious variants of X-linked SSX1 in six unrelated men with asthenoteratozoospermia. SSX1 is a PSG expressed predominantly in the testis, and the SSX family evolutionarily expanded independently in rodents and primates. As the mouse model could not be used for studying SSX1, we used a non-human primate model and tree shrews, which are phylogenetically similar to primates, to knock down (KD) Ssx1 expression in the testes. Consistent with the phenotype observed in humans, both Ssx1-KD models exhibited a reduced sperm motility and abnormal sperm morphology. Further, RNA sequencing indicated that Ssx1 deficiency influenced multiple biological processes during spermatogenesis. Collectively, our experimental observations in humans and cynomolgus monkey and tree shrew models highlight the crucial role of SSX1 in spermatogenesis. Notably, three of the five couples who underwent intra-cytoplasmic sperm injection treatment achieved a successful pregnancy. This study provides important guidance for genetic counseling and clinical diagnosis and, significantly, describes the approaches for elucidating the functions of testis-enriched PSGs in spermatogenesis.
Topics: Animals; Male; Asthenozoospermia; Macaca fascicularis; Primates; Semen; Sperm Motility; Tupaia; Tupaiidae
PubMed: 36796361
DOI: 10.1016/j.ajhg.2023.01.016 -
Cells Jul 2021The etiology of human asthenozoospermia is multifactorial. The need to unveil molecular mechanisms underlying this state of infertility is, thus, impelling. Circular...
The etiology of human asthenozoospermia is multifactorial. The need to unveil molecular mechanisms underlying this state of infertility is, thus, impelling. Circular RNAs (circRNAs) are involved in microRNA (miRNA) inhibition by a sponge activity to protect mRNA targets. All together they form the competitive endogenous RNA network (ceRNET). Recently, we have identified differentially expressed circRNAs (DE-circRNAs) in normozoospermic and asthenozoospermic patients, associated with high-quality (A-spermatozoa) and low-quality (B-spermatozoa) sperm. Here, we carried out a differential analysis of , and mRNA expression in good quality (A-spermatozoa) and low quality (B-spermatozoa) sperm fractions collected from both normozoospermic volunteers and asthenozoospermic patients. These sperm fractions are usually separated on the basis of morphology and motility parameters by a density gradient centrifugation. B-spermatozoa showed low levels of mRNAs. Thus, we identified the possible ceRNET responsible for regulating their expression by focusing on circTRIM2, circEPS15 and circRERE. With the idea that motility perturbations could be rooted in quantitative changes of transcripts in sperm, we evaluated circRNA and mRNA modulation in A-spermatozoa and B-spermatozoa after an oral amino acid supplementation known to improve sperm motility. The profiles of CRISP2, CATSPER1 and PATE1 proteins in the same fractions of sperm well matched with the transcript levels. Our data may strengthen the role of circRNAs in asthenozoospermia and shed light on the molecular pathways linked to sperm motility regulation.
Topics: Adult; Amino Acids; Asthenozoospermia; Calcium Channels; Case-Control Studies; Cell Adhesion Molecules; Dietary Supplements; Gene Expression Regulation, Developmental; Humans; Male; Membrane Proteins; MicroRNAs; RNA, Circular; Semen; Sperm Motility; Spermatozoa; Time Factors; Treatment Outcome; Young Adult
PubMed: 34440724
DOI: 10.3390/cells10081956 -
Advances in Medical Sciences Mar 2017C-type natriuretic peptide (CNP) is a proinflammatory peptide. The highest concentration of CNP is found in male reproductive organs. This study aims to analyze the role...
PURPOSE
C-type natriuretic peptide (CNP) is a proinflammatory peptide. The highest concentration of CNP is found in male reproductive organs. This study aims to analyze the role of N-terminal C-type natriuretic propeptide (NT-proCNP) as a new indicator of asthenozoospermia.
MATERIAL/METHODS
Semen was collected after 3-5 days of sexual abstinence from 86 men. The participants were between 25 and 38 years old, 51 of which had asthenozoospermia and 35 of which had normal sperm motility. Semen was analyzed for the concentrations of NT-proCNP, spermatozoa, percentages of live sperm, and sperm exhibiting a specific type of movement. The laboratory tests and analyses were performed using accepted methods and under appropriate conditions.
RESULTS
A significant difference in the concentration and motility of spermatozoa was observed between the focus and control groups. The concentration of spermatozoa in the focus group was significantly lower than in the control group (median: 38.5 vs. 69.8mln/ml [p=0.016] respectively). The progressive motility of spermatozoa demonstrated a significantly lower performance in the focus group than in the control group (median: 10.4% vs. 45% respectively). The concentration of NT-proCNP was significantly higher in the focus group (median: 29.1 vs. 17.9pmol/l; p<0.001). The Area under the Receiver Operating Characteristic (AUROC) curve for the concentration of NT-proCNP - as an indicator of asthenozoospermia - was 0.733. Participants with a concentration of NT-proCNP higher than 28.8pmol/l had asthenozoospermia with 52.9% sensitivity and 94.3% specificity.
CONCLUSIONS
NT-proCNP - an indicator of inflammatory reaction - should be evaluated as an indicator of asthenozoospermia.
Topics: Adult; Asthenozoospermia; Biomarkers; Case-Control Studies; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, C-Type; Prognosis; Semen; Sperm Motility
PubMed: 28189122
DOI: 10.1016/j.advms.2016.04.002 -
Cell Death & Disease Feb 2023The axonemal dynein arms (outer (ODA) and inner dynein arms (IDAs)) are multiprotein structures organized by light, intermediate, light intermediate (LIC), and heavy...
DNALI1 deficiency causes male infertility with severe asthenozoospermia in humans and mice by disrupting the assembly of the flagellar inner dynein arms and fibrous sheath.
The axonemal dynein arms (outer (ODA) and inner dynein arms (IDAs)) are multiprotein structures organized by light, intermediate, light intermediate (LIC), and heavy chain proteins. They hydrolyze ATP to promote ciliary and flagellar movement. Till now, a variety of dynein protein deficiencies have been linked with asthenospermia (ASZ), highlighting the significance of these structures in human sperm motility. Herein, we detected bi-allelic DNALI1 mutations [c.663_666del (p.Glu221fs)], in an ASZ patient, which resulted in the complete loss of the DNALI1 in the patient's sperm. We identified loss of sperm DNAH1 and DNAH7 rather than DNAH10 in both DNALI1 patient and Dnali1 mice, demonstrating that mammalian DNALI1 is a LIC protein of a partial IDA subspecies. More importantly, we revealed that DNALI1 loss contributed to asymmetries in the most fibrous sheath (FS) of the sperm flagellum in both species. Immunoprecipitation revealed that DNALI1 might interact with the cytoplasmic dynein complex proteins in the testes. Furthermore, DNALI1 loss severely disrupted the transport and assembly of the FS proteins, especially AKAP3 and AKAP4, during flagellogenesis. Hence, DNALI1 may possess a non-classical molecular function, whereby it regulates the cytoplasmic dynein complex that assembles the flagella. We conclude that a DNALI deficiency-induced IDAs injury and an asymmetric FS-driven tail rigid structure alteration may simultaneously cause flagellum immotility. Finally, intracytoplasmic sperm injection (ICSI) can effectively resolve patient infertility. Collectively, we demonstrate that DNALI1 is a newly causative gene for AZS in both humans and mice, which possesses multiple crucial roles in modulating flagellar assembly and motility.
Topics: Animals; Humans; Male; Mice; A Kinase Anchor Proteins; Asthenozoospermia; Axonemal Dyneins; Cytoplasmic Dyneins; Dyneins; Infertility, Male; Mammals; Mutation; Proteins; Semen; Sperm Motility; Sperm Tail
PubMed: 36792588
DOI: 10.1038/s41419-023-05653-y -
Andrology Jan 2023The cellular and molecular mechanisms of the events that help spermatozoa acquire their fertilizing capability during capacitation and acrosome reaction are not...
BACKGROUND
The cellular and molecular mechanisms of the events that help spermatozoa acquire their fertilizing capability during capacitation and acrosome reaction are not completely understood.
OBJECTIVE
This study was performed with a postulation that the identification of sperm proteins and their changes during in vitro capacitation and acrosome reaction will unravel unknown molecular aspects of fertilization that impact male fertility.
MATERIALS AND METHODS
Spermatozoa collected from sequential conditions, that is, separation of ejaculated spermatozoa by Percoll gradient centrifugation, in vitro capacitation, and acrosome reaction were processed for tandem mass spectrometric analysis, followed by protein identification, label-free quantitation, and statistical analysis.
RESULTS AND DISCUSSION
Collectively, a total of 1088 sperm proteins were identified. In comparison to ejaculated spermatozoa, 44 and 141 proteins were differentially expressed in capacitated and acrosome reacted spermatozoa, respectively. A large number of proteins were found downregulated, including clusterin, pyruvate dehydrogenase E1 component, semenogelin-1 and 2, heat shock protein 90, beta-microseminoprotein, and keratin. It was expected as sperm-membrane-associated proteins are removed during capacitation. There were significant proteomic alterations in asthenozoospermia compared to normozoospermia; however, variation was more noticeable among proteins of acrosome reacted spermatozoa and those released during the acrosome reaction. The processes enriched among downregulated proteins in asthenozoospermia included acrosome assembly, binding of spermatozoa to zona pellucida, nucleosome assembly, flagellated sperm motility, protein folding, oxidative phosphorylation, tricarboxylic acid cycle, chromatin silencing, gluconeogenesis, glycolytic process, and glycolysis.
CONCLUSION
The dynamic information generated about proteomic alterations in spermatozoa during capacitation and acrosome reaction and their variability in asthenozoospermia will contribute not only to enhancing our understanding of processes that prepare spermatozoa to acquire fertilization capability but also help in deciphering novel factors of male infertility.
Topics: Male; Humans; Acrosome Reaction; Sperm Capacitation; Asthenozoospermia; Sperm Motility; Proteomics; Semen; Spermatozoa; Acrosome
PubMed: 36057948
DOI: 10.1111/andr.13289