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Life (Basel, Switzerland) Nov 2022The aim of our study was to determine the type and frequency of chromosomal aberrations and polymorphisms in men with different degrees of spermatogenic failure in...
The aim of our study was to determine the type and frequency of chromosomal aberrations and polymorphisms in men with different degrees of spermatogenic failure in comparison to men with normozoospermia, in order to find correlations between cytogenetic findings and the abnormal results of semen analysis. In our study, we performed cytogenetic analysis in 901 infertile men, divided into five groups according to semen analysis-normozoospermia (86), asthenozoospermia (394), oligoasthenozoospermia (182), severe male factor (100), and azoospermia (139). The frequency of polymorphisms was similar in all groups (11-16%, without significant differences). The frequency of numerical and structural aberrations increases with the degree of the spermatogenic failure (3.5% in normozoospermia, 5.6% in asthenozoospermia, 9.8% in oligoasthenozoospermia, 9% in severe male factor, and 13.5% in azoospermia). We found a significantly higher incidence of numerical chromosomal aberrations in severe male factor (7%) and azoospermia (9.3%). Oligoasthenozoospermia occured in 45% of cases with translocation, compared to 20% in the group with a normal karyotype. We revealed that chromosomal translocations are tightly associated with oligoasthenozoospermia, whereas numerical chromosomal aberrations-with severe male factor and azoospermia. The impact of chromosome polymorphisms on male infertility should be studied in greater detail.
PubMed: 36362995
DOI: 10.3390/life12111840 -
Frontiers in Endocrinology 2022Asthenozoospermia is the most common cause of male infertility. Dynein protein arms play a crucial role in the motility of sperm flagella and defects in these proteins...
Asthenozoospermia is the most common cause of male infertility. Dynein protein arms play a crucial role in the motility of sperm flagella and defects in these proteins generally impair the axoneme structure and affect sperm flagella function. In this study, we performed whole exome sequencing for a cohort of 126 infertile patients with asthenozoospermia and identified homozygous mutation in one patient from a consanguineous family. This identified homozygous mutation was verified by Sanger sequencing. analysis showed that this homozygous mutation is very rare, highly pathogenic, and very conserved. Sperm routine analysis confirmed that the motility of the spermatozoa from the patient significantly decreased. Further sperm morphology analysis showed that the spermatozoa from the patient exhibited multiple flagella morphological defects and a specific loss in the inner dynein arms. Fortunately, the patient was able to have his child intracytoplasmic sperm injection treatment. Our study is the first to demonstrate that homozygous mutation may impair the integration of axoneme structure, affect sperm motility and cause asthenoteratozoospermia in human beings.
Topics: Humans; Male; Asthenozoospermia; Axoneme; Dyneins; Mutation; Semen; Sperm Motility
PubMed: 36726469
DOI: 10.3389/fendo.2022.1058651 -
Genes May 2024Several genes are implicated in spermatogenesis and fertility regulation, and these genes are presently being analysed in clinical practice due to their involvement in... (Review)
Review
Several genes are implicated in spermatogenesis and fertility regulation, and these genes are presently being analysed in clinical practice due to their involvement in male factor infertility (MFI). However, there are still few genetic analyses that are currently recommended for use in clinical practice. In this manuscript, we reviewed the genetic causes of qualitative sperm defects. We distinguished between alterations causing reduced sperm motility (asthenozoospermia) and alterations causing changes in the typical morphology of sperm (teratozoospermia). In detail, the genetic causes of reduced sperm motility may be found in the alteration of genes associated with sperm mitochondrial DNA, mitochondrial proteins, ion transport and channels, and flagellar proteins. On the other hand, the genetic causes of changes in typical sperm morphology are related to conditions with a strong genetic basis, such as macrozoospermia, globozoospermia, and acephalic spermatozoa syndrome. We tried to distinguish alterations approved for routine clinical application from those still unsupported by adequate clinical studies. The most important aspect of the study was related to the correct identification of subjects to be tested and the correct application of genetic tests based on clear clinical data. The correct application of available genetic tests in a scenario where reduced sperm motility and changes in sperm morphology have been observed enables the delivery of a defined diagnosis and plays an important role in clinical decision-making. Finally, clarifying the genetic causes of MFI might, in future, contribute to reducing the proportion of so-called idiopathic MFI, which might indeed be defined as a subtype of MFI whose cause has not yet been revealed.
Topics: Humans; Male; Spermatozoa; Sperm Motility; Asthenozoospermia; Infertility, Male; Teratozoospermia; DNA, Mitochondrial; Genetic Testing
PubMed: 38790229
DOI: 10.3390/genes15050600 -
Reproductive Biology and Endocrinology... Dec 2019This article describes the research trends in sperm DNA fragmentation (SDF) over the past 20 years (1999-2018) using a scientometric approach. (Review)
Review
BACKGROUND
This article describes the research trends in sperm DNA fragmentation (SDF) over the past 20 years (1999-2018) using a scientometric approach.
METHODS
A stepwise approach was adopted to retrieve scientometric data (articles per year, authors, affiliations, journals, countries) from Scopus and analyze the publication pattern of SDF with reference to key areas of research in the field of Andrology.
RESULTS
A total of 2121 articles were retrieved related to SDF. Our data revealed an increasing research trend in SDF (n = 33 to n = 173) over the past 20 years (R = 0.894). Most productive country in publications was the USA (n = 450), while Agarwal A. (n = 129) being the most productive author. Most of the articles in SDF were primarily focused on lifestyle (n = 157), asthenozoospermia (n = 135) and varicocele (130). Mechanistic studies on SDF were published twice as much as prognostic/diagnostic studies, with significant emphasis on oxidative stress. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was the most widely used technique to evaluate SDF. Publications on SDF related to assisted reproductive techniques also showed a linear increasing trend (R = 0.933).
CONCLUSIONS
Our analysis revealed an increasing trend in SDF publications predominantly investigating lifestyle, asthenozoospermia and varicocele conditions with TUNEL being the most widely used technique. A substantial increase in research is warranted to establish SDF as prognostic/diagnostic parameter to evaluate clinical scenarios and ART outcomes.
Topics: Asthenozoospermia; Biomedical Research; DNA Damage; DNA Fragmentation; Humans; In Situ Nick-End Labeling; Infertility, Male; Male; National Institutes of Health (U.S.); Publishing; Reproductive Techniques, Assisted; Spermatozoa; United States; Varicocele
PubMed: 31878936
DOI: 10.1186/s12958-019-0550-3 -
Frontiers in Endocrinology 2023In recent years, the quality of male semen has been decreasing, and the number of male infertilities caused by asthenozoospermia is increasing year by year, and the...
INTRODUCTION
In recent years, the quality of male semen has been decreasing, and the number of male infertilities caused by asthenozoospermia is increasing year by year, and the diagnosis and treatment of patients with asthenozoospermia are gradually receiving the attention of the whole society. Due to the unknown etiology and complex pathogenesis, there is no specific treatment for asthenozoospermia. Our previous study found that the administration of chestnut polysaccharide could alter the intestinal microbiota and thus improve the testicular microenvironment, and rescue the impaired spermatogenesis process by enhancing the expression of reproduction-related genes, but its exact metabolome-related repairment mechanism of chestnut polysaccharide is still unclear.
METHODS AND RESULTS
In this study, we studied the blood metabolomic changes of busulfan-induced asthenozoospermia-model mice before and after oral administration of chestnut polysaccharide with the help of metabolome, and screened two key differential metabolites (hydrogen carbonate and palmitic acid) from the set of metabolomic changes; we then analyzed the correlation between several metabolites and between different metabolites and intestinal flora by correlation analysis, and found that palmitic acid in the blood serum of mice after oral administration of chestnut polysaccharide had different degrees of correlation with various metabolites, and palmitic acid level had a significant positive correlation with the abundance of ; finally, we verified the role of palmitic acid in rescuing the damaged spermatogenesis process by using asthenozoospermia-model mice, and screened the key target gene for palmitic acid to play the rescuing effect by integrating the analysis of multiple databases.
DISCUSSION
In conclusion, this study found that chestnut polysaccharide rescued the damaged spermatogenesis in asthenozoospermia-model mice by upregulating palmitic acid level, which will provide theoretical basis and technical support for the use of chestnut polysaccharide in the treatment of asthenozoospermia.
Topics: Humans; Male; Animals; Mice; Asthenozoospermia; Palmitic Acid; Spermatogenesis; Testis; Infertility, Male; Polysaccharides
PubMed: 37484950
DOI: 10.3389/fendo.2023.1222635 -
Basic and Clinical Andrology Oct 2022At present, L-carnitine (LC) and coenzyme Q10 (CoQ10), as used clinically to treat male infertility caused by asthenozoospermia (ASZ) is still mainly administered...
Studies on improving semen quality and increasing pregnancy chances through the in vitro addition of L-carnitine and coenzyme Q10 to semen in patients with asthenozoospermia.
BACKGROUND
At present, L-carnitine (LC) and coenzyme Q10 (CoQ10), as used clinically to treat male infertility caused by asthenozoospermia (ASZ) is still mainly administered orally, but some patients with ASZ still show no significant improvement in sperm motility and spouse pregnancy rate. Prodom is a device used to assist reproduction, which is temporarily fitted onto the penis to facilitate conception by helping the wife inject a certain drug into the vagina. This study used Prodom-assisted LC/CoQ10 in the treatment of patients with ASZ and evaluated the effect of this method on sperm motility and clinical pregnancy, with the goal of finding a comfortable, low-cost, effective method.
RESULTS
During the trial period, 232 cases completed the trial, while 25 cases did not. During in vitro testing, the progressive sperm motility in the LC group, CoQ10 group, LC combined with CoQ10 group, and the semen blank control group was 24.3 ± 4.6% and 38.1 ± 5.1%, 23.0 ± 4.8% and 36.9 ± 4.4%, 28.4 ± 5.0% and 43.8 ± 5.4%, 19.7 ± 4.4% and 26.0 ± 4.9%, respectively. There were statistically significant differences in progressive sperm motility among the groups (all P values < 0.05). The pregnancy rates of the Prodom-assisted LC treatment group, Prodom-assisted CoQ10 treatment group, Prodom-assisted LC combined with CoQ10 treatment group, and oral LC combined with CoQ10 treatment group in the clinical treatment stage were 38.2, 35.4, 57.1, and 30.3%, respectively; the time to conception was 6.1 ± 1.8, 6.2 ± 1.8, 3.4 ± 0.9, and 7.9 ± 2.0, months respectively; and the treatment costs were $2350 ± 457, $2455 ± 434, $1348 ± 411, and $2684 ± 334, respectively. The differences in pregnancy rate, time to conception, and treatment costs among the groups were statistically significant (all P values < 0.05).
CONCLUSIONS
The supplementation of in vitro semen with LC/CoQ10 can improve sperm motility. LC/CoQ10 injected into the spouse's vagina with the assistance of a Prodom can increase the pregnancy rate, shorten the time to conception, and reduce the cost of treatment in patients with ASZ.
TRIAL REGISTRATION
ChiCTR2000040349 (registry: http://www.chictr.org.cn/ ). Date of registration: November 28, 2020.
PubMed: 36192679
DOI: 10.1186/s12610-022-00167-7 -
Medicine Jul 2023Asthenozoospermia (AZS) is the commonest cause of male-related infertility. The patients with AZS easily exhibit infertility, with their wives having spontaneous... (Observational Study)
Observational Study
Asthenozoospermia (AZS) is the commonest cause of male-related infertility. The patients with AZS easily exhibit infertility, with their wives having spontaneous miscarriages or seeking assisted reproductive treatment. Reciprocal chromosomal translocation (RCT) is an important chromosome structural abnormality and has been reported to affect sperm motility. Genetic counseling for male RCT patients with AZS is still a challenge. This study reported 4 RCT carriers, which were 46,XY,t(1;6) (p36.1;p21), 46,XY,t (6;10) (p21;q11.2), 46,XY,t (6;11) (p21;p15), and 46,XY,t (6;17) (p21;q21), respectively. The association between chromosome 6p21 translocation and AZS is discussed, considering 19 published cases as well. In 6 patients with available semen parameters and 4 patients in this study, all of them were diagnosed with AZS. The SLC26A8 gene and the DNAH8 gene located on chromosome 6p21 are closely related to AZS by gene search using OMIM. For the chromosome 6p21 breakpoint, 72 pathogenic genes were found through the DECIPHER search. Gene ontology analysis showed that these target genes have several molecular functions and are strongly involved in various biological processes. The proteins expressed by these genes are involved in multiple cellular components. These results suggest that the breakpoint of chromosome 6p21 in male RCT carriers is closely related to AZS. The breakpoint may disrupt the structure and function of related genes, resulting in reduced sperm motility. Karyotype analysis should be recommended for AZS patients. Chromosomes and breakpoints involved in RCT should be paid attention to in genetic counseling for patients.
Topics: Male; Humans; Asthenozoospermia; Translocation, Genetic; Infertility, Male; Chromosome Aberrations; Karyotype
PubMed: 37417617
DOI: 10.1097/MD.0000000000034318 -
The Journal of Experimental Medicine Feb 2020Asthenozoospermia is a common cause of male infertility, but its etiology remains incompletely understood. We recruited three Pakistani infertile brothers, born to...
Asthenozoospermia is a common cause of male infertility, but its etiology remains incompletely understood. We recruited three Pakistani infertile brothers, born to first-cousin parents, displaying idiopathic asthenozoospermia but no ciliary-related symptoms. Whole-exome sequencing identified a missense variant (c.G5408A, p.C1803Y) in DNAH17, a functionally uncharacterized gene, recessively cosegregating with asthenozoospermia in the family. DNAH17, specifically expressed in testes, was localized to sperm flagella, and the mutation did not alter its localization. However, spermatozoa of all three patients showed higher frequencies of microtubule doublet(s) 4-7 missing at principal piece and end piece than in controls. Mice carrying a homozygous mutation (Dnah17M/M) equivalent to that in patients recapitulated the defects in patients' sperm tails. Further examinations revealed that the doublets 4-7 were destabilized largely due to the storage of sperm in epididymis. Altogether, we first report that a homozygous DNAH17 missense variant specifically induces doublets 4-7 destabilization and consequently causes asthenozoospermia, providing a novel marker for genetic counseling and diagnosis of male infertility.
Topics: Adult; Animals; Asthenozoospermia; Axonemal Dyneins; Cell Line, Tumor; Disease Models, Animal; Female; Genotype; HEK293 Cells; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutation, Missense; Sperm Tail; Spermatozoa; Testis; Transfection
PubMed: 31658987
DOI: 10.1084/jem.20182365 -
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 -
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