Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play p...Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement.Mammalian sperm-associated antigen 17(SPAG17)encodes a conserved axonemal protein of cilia and flagella,forming part of the C1a projection of the central apparatus,with functions related to ciliary/flagellar motility,skeletal growth,and male fertility.This study investigated two novel homozygous SPAG17 mutations(M1:NM_206996.2,c.829+1G>T,p.Asp212_Glu276del;and M2:c.2120del,p.Leu707*)identified in four infertile patients from two consanguineous Pakistani families.These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa.Quantitative real-time polymerase chain reaction(PCR)of patients’spermatozoa also revealed a significant decrease in SPAG17 mRNA expression,and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella.However,no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients.Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls.Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17(SPATA17),a component of the C1a projection,and sperm-associated antigen 6(SPAG6),a marker of the spring layer,revealed disrupted expression of both proteins in the patients’spermatozoa.Altogether,these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme,expanding the phenotypic spectrum of SPAG17 mutations in humans.展开更多
In Burkina Faso, as in other African countries, infertility has become a social burden for the population and a public health problem. Male infertility accounts for 30% to 40% of all infertility cases. The diagnosis o...In Burkina Faso, as in other African countries, infertility has become a social burden for the population and a public health problem. Male infertility accounts for 30% to 40% of all infertility cases. The diagnosis of male infertility or hypofertility is often made by a simple laboratory analysis of sperm to explore sperm parameters. In most African countries, such as Burkina Faso, microbiological analysis in the context of sperm analysis is still not developed, and is carried out solely based on microscopy and traditional culture, which does not allow the growth of fragile and demanding bacteria. Our study investigated the microorganisms of sperm that may be involved in male infertility, using conventional bacteriology techniques and real-time PCR. However, it did not intend to perform a multivariate statistical association analysis to estimate the association of microorganisms with abnormal semen parameters. This prospective cross-sectional pilot study was carried out on patients who visited the bacteriology laboratory of Centre MURAZ, a research Institute in Burkina Faso, for male infertility diagnosis between 2 August and 31 August 2021. Bacteria were isolated and identified using standard bacteriology techniques. In parallel, common pathogenic microorganisms known to be associated with male infertility were targeted and detected in the sperm using a multiplex real-time PCR assay. A total of 38 sperm samples were analyzed by bacteriological culture and bacteria isolated were Staphylococcus aureus (S. aureus) 5.55%, Klebsiella pneumoniae (K. pneumoniae), Enterococcus faecalis (E. faecalis), Streptococcus agalactiae (S. agalactiae) and Staphylococcus hoemalyticus (S. hoemalyticus) respectively 2.70%. Real-time PCR targeted and detected Chlamydia trachomatis (C. trachomatis) at 7.89%, Ureaplasma urealyticum (U. urealyticum) at 21.05%, Ureaplasma parvum (U. parvum) at 18.42%, Mycoplasma hominis (M. hominis) at 15.79%, Mycoplasma genitalium (M. genitalium) at 10.53% and Trichomonas vaginalis (T. vaginalis) at 2.63%. Neisseria gonorrhoeae (N. gonorrhoeae) was targeted by the real-time PCR assay and was not detected (0%) in the tested semen samples. Our study highlights critical limitations of culture performance (low sensitivity), particularly in Burkina Faso, which has a total inability to detect microorganisms (fragile and demanding microorganisms) detected by PCR-based assays. There is therefore an urgent need to at least optimize culture, procedures and algorithms for detection of microorganisms associated with male infertility in clinical laboratories of Burkina Faso. The most effective solution is the routine implementation of molecular diagnostic methods.展开更多
Varicocele(VC)is a common cause of male infertility,yet there is a lack of molecular information for VC-associated male infertility.This study investigated alterations in the seminal plasma metabolomic and lipidomic p...Varicocele(VC)is a common cause of male infertility,yet there is a lack of molecular information for VC-associated male infertility.This study investigated alterations in the seminal plasma metabolomic and lipidomic profiles of infertile male VC patients.Twenty infertile males with VC and twenty-three age-matched healthy controls(HCs)were recruited from Peking Union Medical College Hospital(Beijing,China)between October 2019 and April 2021.Untargeted metabolite and lipid profiles from seminal plasma were analyzed using mass spectrometry.Four hundred and seventy-six metabolites and seventeen lipids were significantly different in infertile male VC patients compared to HCs.The top enriched pathways among these significantly different metabolites are protein digestion and absorption,aminoacyl-transfer RNA(tRNA)biosynthesis,and biosynthesis of amino acids.Different key lipid species,including triglyceride(TG),diacylglycerol(DG),ceramides(Cer),and phosphatidylserine(PS),varied betweenVC and HC groups.The distinct metabolites and lipids were moderately correlated.DL-3-phenyllactic acid is a potential diagnostic biomarker for VC-related male infertility(area under the curve[AUC]=0.893),positively correlating with sperm count,concentration,and motility.Furthermore,DL-3-phenyllactic acid is the only metabolite shared by all four comparisons(VC vs HC,VC-induced oligoasthenospermia[OAS]vs VC-induced asthenospermia[AS],OAS vs HC,and AS vs HC).DL-3-phenyllactic acid significantly decreased in OAS than AS.Metabolite-targeting gene analysis revealed carbonic anhydrase 9(CA9)might be the strongest candidate associated with the onset and severity of VC.The seminal plasma metabolite and lipid profiles of infertile males with VC differ significantly from those of HCs.DL-3-phenyllactic acid could be a promising biomarker.展开更多
Investigating the correlation between micronucleus formation and male infertility has the potential to improve clinical diagnosis and deepen our understanding of pathological progression. Our study enrolled 2252 male ...Investigating the correlation between micronucleus formation and male infertility has the potential to improve clinical diagnosis and deepen our understanding of pathological progression. Our study enrolled 2252 male patients whose semen was analyzed from March 2023 to July 2023. Their clinical data, including semen parameters and age, were also collected. Genetic analysis was used to determine whether the sex chromosome involved in male infertility was abnormal (including the increase, deletion, and translocation of the X and Y chromosomes), and subsequent semen analysis was conducted for clinical grouping purposes. The participants were categorized into five groups: normozoospermia, asthenozoospermia, oligozoospermia, oligoasthenozoospermia, and azoospermia. Patients were randomly selected for further study;41 patients with normozoospermia were included in the control group and 117 patients with non-normozoospermia were included in the study group according to the proportions of all enrolled patients. Cytokinesis-block micronucleus (CBMN) screening was conducted through peripheral blood. Statistical analysis was used to determine the differences in micronuclei (MNi) among the groups and the relationships between MNi and clinical data. There was a significant increase in MNi in infertile men, including those with azoospermia, compared with normozoospermic patients, but there was no significant difference between the genetic and nongenetic groups in azoospermic men. The presence of MNi was associated with sperm concentration, progressive sperm motility, immotile spermatozoa, malformed spermatozoa, total sperm count, and total sperm motility. This study underscores the potential utility of MNi as a diagnostic tool and highlights the need for further research to elucidate the underlying mechanisms of male infertility.展开更多
BACKGROUND Although limited clinical evidence exists,such as case reports of azoospermia treatment in humans using bone marrow aspirate concentrate(BMAC)injection,these findings provide a compelling foundation for exp...BACKGROUND Although limited clinical evidence exists,such as case reports of azoospermia treatment in humans using bone marrow aspirate concentrate(BMAC)injection,these findings provide a compelling foundation for exploring mesenchymal stem cell therapy in male infertility.AIM To evaluate the safety and efficacy of autologous BMAC injection into human testis for men with severe oligospermia or azoospermia over the existing standard of care pharmacotherapy and lifestyle modifications.METHODS We included patients diagnosed with male infertility of the age group between 35–45 years in this trial comparing BMAC injection therapy with pharmacotherapy and lifestyle modifications over a 6-month follow-up period.Semen analysis was used to evaluate the efficacy of the interventions analyzed.RESULTS We enrolled 30 patients in the trial with 10 patients in each arm of the trial.Compared to the baseline,neither the BMAC group(P=0.139)or pharmacotherapy group(P=0.056)nor the lifestyle modification group(P=0.112)demonstrated a statistically significant increase in sperm count at 6 months.However,the BMAC group demonstrated a significant increase in sperm count(mean 19.2 million;P=0.001)compared to the pharmacotherapy group(mean 3.5 million)and lifestyle modification group(mean 2.2 million)at 6 months.Significant improvement was noted in the motility grade(P<0.001)only in the BMAC group while no changes were noted in the other groups.CONCLUSION This trial highlights the potential of autologous BMAC as a promising therapeutic option for male infertility.Despite the absence of significant changes within individual treatment arms,BMAC therapy demonstrated superior efficacy in improving both sperm count and motility compared to standard pharmacotherapy and lifestyle modifications.These findings underscore the potential role of regenerative medicine in addressing severe oligospermia and azoospermia,warranting further research to solidify its clinical applicability.展开更多
Ureaplasma urealyticum(UU)is one of the most commonly occurring pathogens associated with genital tract infections in infertile males,but the impact of seminal UU infection in semen on intrauterine insemination(IUI)ou...Ureaplasma urealyticum(UU)is one of the most commonly occurring pathogens associated with genital tract infections in infertile males,but the impact of seminal UU infection in semen on intrauterine insemination(IUI)outcomes is poorly understood.We collected data from 245 infertile couples who underwent IUI at The First Affiliated Hospital of USTC(Hefei,China)between January 2021 and January 2023.The subjects were classified into two groups according to their UU infection status:the UU-positive group and the UU-negative group.We compared semen parameters,pregnancy outcomes,and neonatal birth outcomes to investigate the impact of UU infection on IUI outcomes.There were no significantly statistical differences in various semen parameters,including semen volume,sperm concentration,total and progressive motility,sperm morphology,leukocyte count,the presence of anti-sperm antibody,and sperm DNA fragmentation index(DFI),between the UU-positive and UU-negative groups of male infertile patients(all P>0.05).However,the high DNA stainability(HDS)status of sperm differed between the UU-positive and UU-negative groups,suggesting that seminal UU infection may affect sperm nuclear maturation(P=0.04).Additionally,there were no significant differences in pregnancy or neonatal birth outcomes between the two groups(all P>0.05).These results suggest that IUI remains a viable and cost-effective option for infertile couples with UU infection who are facing infertility issues.展开更多
Background: According to the World Health Organization, the worldwide prevalence of infertility is 17.5%. The male share of responsibility is undeniable. Several factors, such as smoking, alcoholism, obesity and envir...Background: According to the World Health Organization, the worldwide prevalence of infertility is 17.5%. The male share of responsibility is undeniable. Several factors, such as smoking, alcoholism, obesity and environmental pollution are sources of infertility in men. The aim of this study was to determine the spermological profile of infertile men and the factors associated with sperm parameter abnormalities. Methods: This retrospective study analysed 1000 sperm samples over an 11-year period, from January 2010 to December 2021. Results: The average age was 37.52 ± 8.66 years. Surgical history of varicocele and teratozoospermia were associated (p-value = 0.0001). Candida albicans was associated with a 2.27-fold risk of necrozoospermia and a 3.14-fold risk of oligozoospermia. The link between the reason for requesting a spermogram and the age range between 38 and 47 was significant (p-value Conclusion: Today, lifestyle and environmental pollution play a major role in sperm parameter abnormalities.展开更多
Varicocele,the most common and treatable cause of male infertility,significantly impacts fertility.The pathophysiological mechanisms of varicocele have not been fully understood yet.Recent studies have focused on the ...Varicocele,the most common and treatable cause of male infertility,significantly impacts fertility.The pathophysiological mechanisms of varicocele have not been fully understood yet.Recent studies have focused on the pathophysiology of varicocele-induced infertility,highlighting inflammation and oxidative stress as key contributing factors.We reviewed recent research on the roles of inflammation and oxidative stress in the pathophysiology of varicocele and found that they negatively impact semen parameters,spermatogenesis,and testicular and epididymal function.In addition,this article summarizes the related factors of inflammation and oxidative stress caused by varicocele.Finally,a brief consideration on the treatments to address inflammation and oxidative stress is proposed.This review may provide treatment options and targets for varicocele-induced infertility.However,the relationship between inflammation and oxidative stress in varicocele still needs further study.展开更多
Circular RNAs(circRNAs)are key regulators of reproductive biology.However,limited information is available regarding circRNA expression profiles in seminal plasma samples from individuals with male infertility.The pre...Circular RNAs(circRNAs)are key regulators of reproductive biology.However,limited information is available regarding circRNA expression profiles in seminal plasma samples from individuals with male infertility.The present study aimed to identify circRNAs associated with infertility in seminal plasma samples and to clarify their potential as biomarkers,as well as the possible molecular mechanisms underlying their functions.Nextgeneration RNA sequencing was conducted to analyze circRNA profiles in seminal plasma from healthy controls,oligoasthenospermia(OAZ)patients,and non-obstructive azoospermia(NOA)patients.Bioinformatics analysis revealed that 637 circRNAs were differentially expressed between OAZ and control subjects,and 272 circRNAs were differentially expressed between NOA and control subjects.The expression of key circRNAs(hsa-SAP130_0002,hsa-TRPC1_0001,hsa-FBRS_0001,hsa-ACACA_0025,hsa-UTRN_0042,and hsa-ZNF532_0023)was then validated by qPCR,and their diagnostic accuracy for infertility was confirmed through receiver operating characteristic curve analysis.Additionally,a possible circRNA-miRNA-mRNA regulatory network was constructed for these candidate biomarkers.Collectively,this study identifies a novel set of circRNAs with potential as diagnostic biomarkers for male infertility and provides molecular insights that may facilitate both diagnostic and therapeutic efforts.展开更多
Objective:To investigate the levels of seminal plasma exosomes and the expression of the SRD5A2 gene in Iraqi men with different types of male infertility(asthenozoospermia,oligozoospermia,and azoospermia),and to expl...Objective:To investigate the levels of seminal plasma exosomes and the expression of the SRD5A2 gene in Iraqi men with different types of male infertility(asthenozoospermia,oligozoospermia,and azoospermia),and to explore the regulatory role of selected microRNAs(miRNAs)in the modulation of SRD5A2 gene expression.Methods:A total of 90 male participants were categorized into four groups:asthenozoospermia(n=24),oligozoospermia(n=24),azoospermia(n=18),and normozoospermia(n=24).Seminal plasma exosome levels were quantified using ELISA.RNA,including miRNAs,was extracted,followed by cDNA synthesis.The expression of SRD5A2 mRNA and five selected miRNAs(miR-6090,hsa-miR-5189-5p,miR-23a-5p,miR-1914-3p,and miR-4540)was evaluated using qRT-PCR.Correlation analyses were conducted between exosome levels,miRNA expression,and SRD5A2 expression.Results:Infertile men exhibited significantly lower seminal exosome levels than normozoospermic men(P<0.01).The expression of SRD5A2 mRNA was decreased in asthenozoospermic and oligozoospermic men but elevated in azoospermic men.Elevated levels of hsa-miR-5189-5p,miR-6090,and miR-23a-5p were observed in infertile groups.Correlation analysis revealed a significant negative relationship between these miRNAs and SRD5A2 expression in asthenozoospermic and oligozoospermic men,but a positive correlation in azoospermic men.Exosome levels were also significantly correlated with the expression of these miRNAs,suggesting their role as molecular carriers in regulating gene expression.Conclusions:This study highlights the potential role of seminal exosomes and specific miRNAs in regulating SRD5A2 gene expression among infertile men.The altered levels of exosomes and dysregulated miRNA expression,particularly hsa-miR-5189-5p and miR-6090,may serve as novel biomarkers for the diagnosis and management of male infertility.Further research is warranted to validate these findings and explore their therapeutic implications.展开更多
Multiple morphological abnormalities of sperm flagella(MMAF)is a severe form of asthenoteratozoospermia,characterized by morphological abnormalities and reduced motility of sperm,causing male infertility.Although appr...Multiple morphological abnormalities of sperm flagella(MMAF)is a severe form of asthenoteratozoospermia,characterized by morphological abnormalities and reduced motility of sperm,causing male infertility.Although approximately 60%of MMAF cases can be explained genetically,the etiology of the remaining cases is unclear.Here,we identified two novel compound heterozygous variants in the gene,dynein axonemal heavy chain 10(DNAH10),in three patients from two unrelated Pakistani families using whole-exome sequencing(WES),including one compound heterozygous mutation(DNAH10:c.9409C>A[p.P3137T];c.12946G>C[p.D4316H])in family 1 and another compound heterozygous mutation(DNAH10:c.8849G>A[p.G2950D];c.11509C>T[p.R3687W])in family 2.All the identified variants are absent or rare in public genome databases and are predicted to have deleterious effects according to multiple bioinformatic tools.Sanger sequencing revealed that these variants follow an autosomal recessive mode of inheritance.Hematoxylin and eosin(H&E)staining revealed MMAF,including sperm head abnormalities,in the patients.In addition,immunofluorescence staining revealed loss of DNAH10 protein signals along sperm flagella.These findings broaden the spectrum of DNAH10 variants and expand understanding of the genetic basis of male infertility associated with the MMAF phenotype.展开更多
In recent years, social research surrounding the consequences of infertility has increasingly focused on the male perspective;however, a gap exists in the understanding of men’s experiences of male infertility treatm...In recent years, social research surrounding the consequences of infertility has increasingly focused on the male perspective;however, a gap exists in the understanding of men’s experiences of male infertility treatment. This review aims to synthesize theexisting evidence concerning the psychological, social, and sexual burden of male infertility treatment on men, as well as patientneeds during clinical care. A systematic search identified 12 studies that are diverse in design, setting, and methods. Psychologicalevaluations have found that urological surgery may have a lasting impact on infertility-specific stress, and treatment failure canlead to feelings of depression, grief, and inadequacy. Men tended to have an avoidant coping mechanism throughout fertilitytreatment, and their self-esteem, relationship quality, and sexual functions can be tied to outcomes of treatment. Partner bonds canbe strengthened by mutual support and enhanced communication;couple separation, however, has been noted as a predominantreason for discontinuing male infertility treatment and may be associated with difficult circumstances surrounding severe maleinfertility. Surgical treatments can affect the sexual functioning of infertile men;however, the impact of testicular sperm extractionoutcomes appears to be psychologically driven whereas the improvements after microsurgical varicocelectomy are only evident inhypogonadal men. Clinically, there is a need for better inclusion, communication, education, and resource provision, to addressreported issues of marginalization and uncertainty in men. Routine psychosocial screening in cases of severe male infertility andfollow-up in cases of surgical treatment failure are likely beneficial.展开更多
Infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family. Despite this, the molecular and genetic factors underlying the cause of infertility remain large...Infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family. Despite this, the molecular and genetic factors underlying the cause of infertility remain largely undiscovered. Nevertheless, more and more genetic factors associated with infertility are being identified. This review will focus on our current understanding of the chromosomal basis of male infertility specifically： chromosomal aneuploidy, structural and numerical karyotype abnormalities and Y chromosomal microdeletions. Chromosomal aneuploidy is the leading cause of pregnancy loss and developmental disabilities in humans. Aneuploidy is predominantly maternal in origin, but concerns have been raised regarding the safety of intracytoplasmic sperm injection as infertile men have significantly higher levels of sperm aneuploidy compared to their fertile counterparts. Males with numerical or structural karyotype abnormalities are also at an increased risk of producing aneuploid sperm. Our current understanding of how sperm aneuploidy translates to embryo aneuploidy will be reviewed, as well as the application of preimplantation genetic diagnosis （PGD） in such cases. Clinical recommendations where possible will be made, as well as discussion of the use of emerging array technology in PGD and its potential applications in male infertility.展开更多
While we may be comfortable with an allopathic approach to male infertility, we are also responsible for knowledge about lifestyle modifications and holistic, complementary, and alternative therapies that are used by ...While we may be comfortable with an allopathic approach to male infertility, we are also responsible for knowledge about lifestyle modifications and holistic, complementary, and alternative therapies that are used by many of our patients. This paper provides an evidence-based review separating fact from fiction for several of these therapies. There is sufficient literature to support weight reduction by diet and exercise, smoking cessation, and alcohol moderation. Supplements that have demonstrated positive effects on male fertility on small randomized controlled trial （RCT） include aescin, coenzyme Qlo, glutathione, Korean red ginseng, L-carnitine, nigella sativa, omega-3, selenium, a combination of zinc and folate, and the Menevit antioxidant. There is no support for the use of Vitamin C, Vitamin E, or saffron. The data for Chinese herbal medications, acupuncture, mind-body practice, scrotal cooling, and faith-based healing are sparse or inconclusive.展开更多
Human papillomavirus （HPV） is one of the most common sexually transmitted diseases which comprises a group of small DNA viruses that infect both cutaneous and mucous squamous epithelia. Liquid bead microarray techno...Human papillomavirus （HPV） is one of the most common sexually transmitted diseases which comprises a group of small DNA viruses that infect both cutaneous and mucous squamous epithelia. Liquid bead microarray technology （LBMA） were used to evaluate 24 HPV genotypes in confirmed fertile and infertile males of North China so that the effects of HPV infection on semen parameters and relationship with male infertility could be discussed. A total of 1138 subjects were recruited in this study; 142 were HPV-positive （12.48%）. Among 523 confirmed fertile males, only 35 were HPV-positive （6.70%）, and two of them had multiple infections. Among 615 infertile males, 107 were HPV-positive （17.4%）, and 29 of them had multiple infections. Infertile males had a relatively high HPV infection rate compared with confirmed fertile males. Sperm progressive motility （PR） and the normal morphology rate were significantly decreased in HPV-positive subjects. HPV-45, HPV-52, HPV-18, HPV-59 and HPV-16 infections were more frequently in infertile males. Hence, HPV infection is closely related to male infertility which will decrease sperm PR and morphology. HPV-45, HPV-52, HPV-18, HPV-59 and HPV-16 infection seems to be major risk factors.展开更多
Multiplex polymerase chain reaction （PCR） has been widely used to detect Y-chromosome micredeletions, which is one of the major causes of male infertility. Both the European Academy of Andrology （EAA） and the Euro...Multiplex polymerase chain reaction （PCR） has been widely used to detect Y-chromosome micredeletions, which is one of the major causes of male infertility. Both the European Academy of Andrology （EAA） and the European Molecular Genetics Quality Network （EMQN） have recommended the use of sY84 and sY86 markers for the detection of azoospermia factor a （AZFa） microdeletion during DNA testing for male infertility. In this study, a large-scale analysis of AZF microdeletion in a total of 630 Chinese males, including healthy semen donors （n=200）, infertile males with normal sperm count （n=226） and patients with either nonobstructive azoospermia or severe oligozoospermia （n=204）, was performed. A series of nine sequence-tagged site （STS） markers from the AZF region of the Y chromosome was used to detect microdeletions. All primers were designed based on the recommendations of the National Center for Biotechnology Information. An unusually high incidence （73/630, 11.6%） of sY84-absent but sY86-present genotypes was observed in the AZFa microdeletion screening. Sequencing the sY84-flanking region revealed a total of 73 patients with sY84-absent but sY86-present genotypes have a T-to-G transversion at the fifth base from the 5＇ end of the reverse sY84 primer. These prevalent false positives, which were not only observed in infertile men, but also observed in donors, resulted from a single-nucleotide polymorphism （SNP） named rs72609647 in the targeting sequence of the reverse sY84 primer. Our study suggests that a pre-screening of existence of rs72609647 polymorphism can prevent the frequent false positive results of AZFa microdeletions detection in the infertile Chinese males. Given the SNP rs72609647 was recently found in a deep sequencing of a Chinese individual, the current EAA and EMQN standards may need to be scrutinized among different populations to avoid the potential genetic variations in the primer binding sequences.展开更多
The Y chromosome evolves from an autochromosome and accumulates male-related genes including sex-determining region of Y-chromosome （SRY） and several spermatogenesis-related genes. The human Y chromosome （60 Mb lon...The Y chromosome evolves from an autochromosome and accumulates male-related genes including sex-determining region of Y-chromosome （SRY） and several spermatogenesis-related genes. The human Y chromosome （60 Mb long） is largely composed of repetitive sequences that give it a heterochromatic appearance, and it consists of pseudoautosomal, euchromatic, and heterochromatic regions. Located on the two extremities of the Y chromosome, pseudoautosomal regions 1 and 2 （PAR1 and PAR2, 2.6 Mb and 320 bp long, respectively） are homologs with the termini of the X chromosome. The euchromatic region and some of the repeat-rich heterochromatic parts of the Y chromosome are called ＂male-specific Y＂ （MSY）, which occupy more than 95% of the whole Y chromosome. After evolution, the Y chromosome becomes the smallest in size with the least number of genes but with the most number of copies of genes that are mostly spermatogenesis-related. The Y chromosome is characterized by highly repetitive sequences （including direct repeats, inverted repeats, and palindromes） and high polymorphism. Several gene rearrangements on the Y chromosome occur during evolution owing to its specific gene structure. The consequences of such rearrangements are not only loss but also gain of specific genes. One hundred and fifty three haplotypes have been discovered in the human Y chromosome. The structure of the Y chromosome in the GenBank belongs to haplotype R1. There are 220 genes （104 coding genes, 111 pseudogenes, and 5 other uncategorized genes） according to the most recent count. The 104 coding genes encode a total of about 48 proteins/protein families （including putative proteins/protein families）. Among them, 16 gene products have been discovered in the azoospermia factor region （AZF） and are related to spermatogenesis. It has been discovered that one subset of gene rearrangements on the Y chromosome, ＂micro-deletions＂, is a major cause of male infertility in some populations. However, controversies exist about different Y chromosome haplotypes. Six AZFs of the Y chromosome have been discovered including AZFa, AZFb, AZFc, and their combinations AZFbc, AZFabc, and partial AZFc called AZFc/gr/gr. Different deletions in AZF lead to different content spermatogenesis loss from teratozoospermia to infertility in different populations depending on their Y haplotypes. This article describes the structure of the human Y chromosome and investigates the causes of micro-deletions and their relationship with male infertility from the view of chromosome evolution. After analysis of the relationship between AZFc and male infertility, we concluded that spermatogenesis is controlled by a network of genes, which may locate on the Y chromosome, the autochromosomes, or even on the X chromosome. Further investigation of the molecular mechanisms underlying male fertility/infertility will facilitate our knowledge of functional genomics.展开更多
<abstract>During spermiogenesis, the protamine proteins play an integral role in spermatid chromatin compaction. Recent research has focused on many facets of protamine biology, including protamine gene and prot...<abstract>During spermiogenesis, the protamine proteins play an integral role in spermatid chromatin compaction. Recent research has focused on many facets of protamine biology, including protamine gene and protein structure/ function relationships, mechanisms of protamine expression regulation and involvement of the protamines in male fertility. In this paper, we review our current understanding of the structure and function of the protamine-1 (P1) and protamine-2 (P2) proteins and genes, the expression and regulation of these genes and the relationship between the protamines and male fertility. In addition, we offer a brief outlook on future investigation into protamine proteins.展开更多
Excessive amounts of reactive oxygen species （ROS） cause a state of oxidative stress, which result in sperm membrane lipid peroxidation, DNA damage and apoptosis, leading to decreased sperm viability and motility. E...Excessive amounts of reactive oxygen species （ROS） cause a state of oxidative stress, which result in sperm membrane lipid peroxidation, DNA damage and apoptosis, leading to decreased sperm viability and motility. Elevated levels of ROS are a major cause of idiopathic male factor infertility, which is an increasingly common problem today. Lycopene, the most potent singlet oxygen quencher of all carotenoids, is a possible treatment option for male infertility because of its antioxidant properties. By reacting with and neutralizing free radicals, lycopene could reduce the incidence of oxidative stress and thus, lessen the damage that would otherwise be inflicted on spermatozoa. It is postulated that lycopene may have other beneficial effects via nonoxidative mechanisms in the testis, such as gap junction communication, modulation of gene expression, regulation of the cell cycle and immunoenhancement. Various lycopene supplementation studies conducted on both humans and animals have shown promising results in alleviating male infertility--lipid peroxidation and DNA damage were decreased, while sperm count and viability, and general immunity were increased. Improvement of these parameters indicates a reduction in oxidative stress, and thus the spermatozoa is less vulnerable to oxidative damage, which increases the chances of a normal sperm fertilizing the egg. Human trials have reported improvement in sperm parameters and pregnancy rates with supplementation of 4-8 mg of lycopene daily for 3-12 months. However, further detailed and extensive research is still required to determine the dosage and the usefulness of lycopene as a treatment for male infertility.展开更多
Male factor contributes to 50%-60% of overall infertility but is solely responsible in only 20% of couples. Although most male factor infertility is ascertained from an abnormal semen analysis, other male factors can ...Male factor contributes to 50%-60% of overall infertility but is solely responsible in only 20% of couples. Although most male factor infertility is ascertained from an abnormal semen analysis, other male factors can be contributory especially if the sample returns normal. Male infertility can be due to identifiable hormonal or anatomical etiologies that may be reversible or irreversible. This manuscript will highlight existing guidelines and our recommendations for hormone evaluation for male infertility and empiric therapies including multivitamins, estrogen receptor modulators （clomiphene）, estrogen conversion blockers （anastrozole）, and hormone replacement.展开更多
基金supported by the National Natural Science Foundation of China(No.82171599 and No.32270901)the National Key Research and Developmental Program of China(2022YFC2702601 and 2022YFA0806303)the Global Select Project(DJKLX-2022010)of the Institute of Health and Medicine,Hefei Comprehensive National Science Center.
文摘Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement.Mammalian sperm-associated antigen 17(SPAG17)encodes a conserved axonemal protein of cilia and flagella,forming part of the C1a projection of the central apparatus,with functions related to ciliary/flagellar motility,skeletal growth,and male fertility.This study investigated two novel homozygous SPAG17 mutations(M1:NM_206996.2,c.829+1G>T,p.Asp212_Glu276del;and M2:c.2120del,p.Leu707*)identified in four infertile patients from two consanguineous Pakistani families.These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa.Quantitative real-time polymerase chain reaction(PCR)of patients’spermatozoa also revealed a significant decrease in SPAG17 mRNA expression,and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella.However,no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients.Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls.Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17(SPATA17),a component of the C1a projection,and sperm-associated antigen 6(SPAG6),a marker of the spring layer,revealed disrupted expression of both proteins in the patients’spermatozoa.Altogether,these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme,expanding the phenotypic spectrum of SPAG17 mutations in humans.
文摘In Burkina Faso, as in other African countries, infertility has become a social burden for the population and a public health problem. Male infertility accounts for 30% to 40% of all infertility cases. The diagnosis of male infertility or hypofertility is often made by a simple laboratory analysis of sperm to explore sperm parameters. In most African countries, such as Burkina Faso, microbiological analysis in the context of sperm analysis is still not developed, and is carried out solely based on microscopy and traditional culture, which does not allow the growth of fragile and demanding bacteria. Our study investigated the microorganisms of sperm that may be involved in male infertility, using conventional bacteriology techniques and real-time PCR. However, it did not intend to perform a multivariate statistical association analysis to estimate the association of microorganisms with abnormal semen parameters. This prospective cross-sectional pilot study was carried out on patients who visited the bacteriology laboratory of Centre MURAZ, a research Institute in Burkina Faso, for male infertility diagnosis between 2 August and 31 August 2021. Bacteria were isolated and identified using standard bacteriology techniques. In parallel, common pathogenic microorganisms known to be associated with male infertility were targeted and detected in the sperm using a multiplex real-time PCR assay. A total of 38 sperm samples were analyzed by bacteriological culture and bacteria isolated were Staphylococcus aureus (S. aureus) 5.55%, Klebsiella pneumoniae (K. pneumoniae), Enterococcus faecalis (E. faecalis), Streptococcus agalactiae (S. agalactiae) and Staphylococcus hoemalyticus (S. hoemalyticus) respectively 2.70%. Real-time PCR targeted and detected Chlamydia trachomatis (C. trachomatis) at 7.89%, Ureaplasma urealyticum (U. urealyticum) at 21.05%, Ureaplasma parvum (U. parvum) at 18.42%, Mycoplasma hominis (M. hominis) at 15.79%, Mycoplasma genitalium (M. genitalium) at 10.53% and Trichomonas vaginalis (T. vaginalis) at 2.63%. Neisseria gonorrhoeae (N. gonorrhoeae) was targeted by the real-time PCR assay and was not detected (0%) in the tested semen samples. Our study highlights critical limitations of culture performance (low sensitivity), particularly in Burkina Faso, which has a total inability to detect microorganisms (fragile and demanding microorganisms) detected by PCR-based assays. There is therefore an urgent need to at least optimize culture, procedures and algorithms for detection of microorganisms associated with male infertility in clinical laboratories of Burkina Faso. The most effective solution is the routine implementation of molecular diagnostic methods.
基金supported by the National Key Research and Development Program of China(No.2018YFE0207300)Beijing Natural Science Foundation(No.M23008)+1 种基金the National High Level Hospital Clinical Research Funding(No.2022-PUMCH-B-124)the National High Level Hospital Clinical Research Funding(No.2022-PUMCH-A-057)。
文摘Varicocele(VC)is a common cause of male infertility,yet there is a lack of molecular information for VC-associated male infertility.This study investigated alterations in the seminal plasma metabolomic and lipidomic profiles of infertile male VC patients.Twenty infertile males with VC and twenty-three age-matched healthy controls(HCs)were recruited from Peking Union Medical College Hospital(Beijing,China)between October 2019 and April 2021.Untargeted metabolite and lipid profiles from seminal plasma were analyzed using mass spectrometry.Four hundred and seventy-six metabolites and seventeen lipids were significantly different in infertile male VC patients compared to HCs.The top enriched pathways among these significantly different metabolites are protein digestion and absorption,aminoacyl-transfer RNA(tRNA)biosynthesis,and biosynthesis of amino acids.Different key lipid species,including triglyceride(TG),diacylglycerol(DG),ceramides(Cer),and phosphatidylserine(PS),varied betweenVC and HC groups.The distinct metabolites and lipids were moderately correlated.DL-3-phenyllactic acid is a potential diagnostic biomarker for VC-related male infertility(area under the curve[AUC]=0.893),positively correlating with sperm count,concentration,and motility.Furthermore,DL-3-phenyllactic acid is the only metabolite shared by all four comparisons(VC vs HC,VC-induced oligoasthenospermia[OAS]vs VC-induced asthenospermia[AS],OAS vs HC,and AS vs HC).DL-3-phenyllactic acid significantly decreased in OAS than AS.Metabolite-targeting gene analysis revealed carbonic anhydrase 9(CA9)might be the strongest candidate associated with the onset and severity of VC.The seminal plasma metabolite and lipid profiles of infertile males with VC differ significantly from those of HCs.DL-3-phenyllactic acid could be a promising biomarker.
基金supported by the National Natural Science Foundation of China(No.32070582)the Joint Foundation of He Lin Academical Workstation of the Third Affiliated Hospital of Guangzhou Medical University(2023HLLH01)the Plan on enhancing scientific research in GMU(2024SRP125).
文摘Investigating the correlation between micronucleus formation and male infertility has the potential to improve clinical diagnosis and deepen our understanding of pathological progression. Our study enrolled 2252 male patients whose semen was analyzed from March 2023 to July 2023. Their clinical data, including semen parameters and age, were also collected. Genetic analysis was used to determine whether the sex chromosome involved in male infertility was abnormal (including the increase, deletion, and translocation of the X and Y chromosomes), and subsequent semen analysis was conducted for clinical grouping purposes. The participants were categorized into five groups: normozoospermia, asthenozoospermia, oligozoospermia, oligoasthenozoospermia, and azoospermia. Patients were randomly selected for further study;41 patients with normozoospermia were included in the control group and 117 patients with non-normozoospermia were included in the study group according to the proportions of all enrolled patients. Cytokinesis-block micronucleus (CBMN) screening was conducted through peripheral blood. Statistical analysis was used to determine the differences in micronuclei (MNi) among the groups and the relationships between MNi and clinical data. There was a significant increase in MNi in infertile men, including those with azoospermia, compared with normozoospermic patients, but there was no significant difference between the genetic and nongenetic groups in azoospermic men. The presence of MNi was associated with sperm concentration, progressive sperm motility, immotile spermatozoa, malformed spermatozoa, total sperm count, and total sperm motility. This study underscores the potential utility of MNi as a diagnostic tool and highlights the need for further research to elucidate the underlying mechanisms of male infertility.
文摘BACKGROUND Although limited clinical evidence exists,such as case reports of azoospermia treatment in humans using bone marrow aspirate concentrate(BMAC)injection,these findings provide a compelling foundation for exploring mesenchymal stem cell therapy in male infertility.AIM To evaluate the safety and efficacy of autologous BMAC injection into human testis for men with severe oligospermia or azoospermia over the existing standard of care pharmacotherapy and lifestyle modifications.METHODS We included patients diagnosed with male infertility of the age group between 35–45 years in this trial comparing BMAC injection therapy with pharmacotherapy and lifestyle modifications over a 6-month follow-up period.Semen analysis was used to evaluate the efficacy of the interventions analyzed.RESULTS We enrolled 30 patients in the trial with 10 patients in each arm of the trial.Compared to the baseline,neither the BMAC group(P=0.139)or pharmacotherapy group(P=0.056)nor the lifestyle modification group(P=0.112)demonstrated a statistically significant increase in sperm count at 6 months.However,the BMAC group demonstrated a significant increase in sperm count(mean 19.2 million;P=0.001)compared to the pharmacotherapy group(mean 3.5 million)and lifestyle modification group(mean 2.2 million)at 6 months.Significant improvement was noted in the motility grade(P<0.001)only in the BMAC group while no changes were noted in the other groups.CONCLUSION This trial highlights the potential of autologous BMAC as a promising therapeutic option for male infertility.Despite the absence of significant changes within individual treatment arms,BMAC therapy demonstrated superior efficacy in improving both sperm count and motility compared to standard pharmacotherapy and lifestyle modifications.These findings underscore the potential role of regenerative medicine in addressing severe oligospermia and azoospermia,warranting further research to solidify its clinical applicability.
基金supported by the National Natural Science Foundation of China(No.82301800 and No.82101685).
文摘Ureaplasma urealyticum(UU)is one of the most commonly occurring pathogens associated with genital tract infections in infertile males,but the impact of seminal UU infection in semen on intrauterine insemination(IUI)outcomes is poorly understood.We collected data from 245 infertile couples who underwent IUI at The First Affiliated Hospital of USTC(Hefei,China)between January 2021 and January 2023.The subjects were classified into two groups according to their UU infection status:the UU-positive group and the UU-negative group.We compared semen parameters,pregnancy outcomes,and neonatal birth outcomes to investigate the impact of UU infection on IUI outcomes.There were no significantly statistical differences in various semen parameters,including semen volume,sperm concentration,total and progressive motility,sperm morphology,leukocyte count,the presence of anti-sperm antibody,and sperm DNA fragmentation index(DFI),between the UU-positive and UU-negative groups of male infertile patients(all P>0.05).However,the high DNA stainability(HDS)status of sperm differed between the UU-positive and UU-negative groups,suggesting that seminal UU infection may affect sperm nuclear maturation(P=0.04).Additionally,there were no significant differences in pregnancy or neonatal birth outcomes between the two groups(all P>0.05).These results suggest that IUI remains a viable and cost-effective option for infertile couples with UU infection who are facing infertility issues.
文摘Background: According to the World Health Organization, the worldwide prevalence of infertility is 17.5%. The male share of responsibility is undeniable. Several factors, such as smoking, alcoholism, obesity and environmental pollution are sources of infertility in men. The aim of this study was to determine the spermological profile of infertile men and the factors associated with sperm parameter abnormalities. Methods: This retrospective study analysed 1000 sperm samples over an 11-year period, from January 2010 to December 2021. Results: The average age was 37.52 ± 8.66 years. Surgical history of varicocele and teratozoospermia were associated (p-value = 0.0001). Candida albicans was associated with a 2.27-fold risk of necrozoospermia and a 3.14-fold risk of oligozoospermia. The link between the reason for requesting a spermogram and the age range between 38 and 47 was significant (p-value Conclusion: Today, lifestyle and environmental pollution play a major role in sperm parameter abnormalities.
文摘Varicocele,the most common and treatable cause of male infertility,significantly impacts fertility.The pathophysiological mechanisms of varicocele have not been fully understood yet.Recent studies have focused on the pathophysiology of varicocele-induced infertility,highlighting inflammation and oxidative stress as key contributing factors.We reviewed recent research on the roles of inflammation and oxidative stress in the pathophysiology of varicocele and found that they negatively impact semen parameters,spermatogenesis,and testicular and epididymal function.In addition,this article summarizes the related factors of inflammation and oxidative stress caused by varicocele.Finally,a brief consideration on the treatments to address inflammation and oxidative stress is proposed.This review may provide treatment options and targets for varicocele-induced infertility.However,the relationship between inflammation and oxidative stress in varicocele still needs further study.
基金funded by the National Key R&D Program of China(Grant No.2022YFC2702800 to Y.C.)the National Natural Science Foundation of China(Grant No.82122025 to Y.Y.)the National Key R&D Program of China(Grant No.2021YFC2700200 to Y.C.).
文摘Circular RNAs(circRNAs)are key regulators of reproductive biology.However,limited information is available regarding circRNA expression profiles in seminal plasma samples from individuals with male infertility.The present study aimed to identify circRNAs associated with infertility in seminal plasma samples and to clarify their potential as biomarkers,as well as the possible molecular mechanisms underlying their functions.Nextgeneration RNA sequencing was conducted to analyze circRNA profiles in seminal plasma from healthy controls,oligoasthenospermia(OAZ)patients,and non-obstructive azoospermia(NOA)patients.Bioinformatics analysis revealed that 637 circRNAs were differentially expressed between OAZ and control subjects,and 272 circRNAs were differentially expressed between NOA and control subjects.The expression of key circRNAs(hsa-SAP130_0002,hsa-TRPC1_0001,hsa-FBRS_0001,hsa-ACACA_0025,hsa-UTRN_0042,and hsa-ZNF532_0023)was then validated by qPCR,and their diagnostic accuracy for infertility was confirmed through receiver operating characteristic curve analysis.Additionally,a possible circRNA-miRNA-mRNA regulatory network was constructed for these candidate biomarkers.Collectively,this study identifies a novel set of circRNAs with potential as diagnostic biomarkers for male infertility and provides molecular insights that may facilitate both diagnostic and therapeutic efforts.
文摘Objective:To investigate the levels of seminal plasma exosomes and the expression of the SRD5A2 gene in Iraqi men with different types of male infertility(asthenozoospermia,oligozoospermia,and azoospermia),and to explore the regulatory role of selected microRNAs(miRNAs)in the modulation of SRD5A2 gene expression.Methods:A total of 90 male participants were categorized into four groups:asthenozoospermia(n=24),oligozoospermia(n=24),azoospermia(n=18),and normozoospermia(n=24).Seminal plasma exosome levels were quantified using ELISA.RNA,including miRNAs,was extracted,followed by cDNA synthesis.The expression of SRD5A2 mRNA and five selected miRNAs(miR-6090,hsa-miR-5189-5p,miR-23a-5p,miR-1914-3p,and miR-4540)was evaluated using qRT-PCR.Correlation analyses were conducted between exosome levels,miRNA expression,and SRD5A2 expression.Results:Infertile men exhibited significantly lower seminal exosome levels than normozoospermic men(P<0.01).The expression of SRD5A2 mRNA was decreased in asthenozoospermic and oligozoospermic men but elevated in azoospermic men.Elevated levels of hsa-miR-5189-5p,miR-6090,and miR-23a-5p were observed in infertile groups.Correlation analysis revealed a significant negative relationship between these miRNAs and SRD5A2 expression in asthenozoospermic and oligozoospermic men,but a positive correlation in azoospermic men.Exosome levels were also significantly correlated with the expression of these miRNAs,suggesting their role as molecular carriers in regulating gene expression.Conclusions:This study highlights the potential role of seminal exosomes and specific miRNAs in regulating SRD5A2 gene expression among infertile men.The altered levels of exosomes and dysregulated miRNA expression,particularly hsa-miR-5189-5p and miR-6090,may serve as novel biomarkers for the diagnosis and management of male infertility.Further research is warranted to validate these findings and explore their therapeutic implications.
基金supported by the National Natural Science Foundation of China(No.32100689)the National Key Research and Development Program of China(No.2021YFC2700202,No.2022YFA0806303,and No.2022YFC2702601)+1 种基金the Global Select Project(No.DJK-LX-2022010)of the Institute of Health and MedicineHefei Comprehensive National Science Center,and the Joint Fund for New Medicine of USTC(No.YD9100002034).
文摘Multiple morphological abnormalities of sperm flagella(MMAF)is a severe form of asthenoteratozoospermia,characterized by morphological abnormalities and reduced motility of sperm,causing male infertility.Although approximately 60%of MMAF cases can be explained genetically,the etiology of the remaining cases is unclear.Here,we identified two novel compound heterozygous variants in the gene,dynein axonemal heavy chain 10(DNAH10),in three patients from two unrelated Pakistani families using whole-exome sequencing(WES),including one compound heterozygous mutation(DNAH10:c.9409C>A[p.P3137T];c.12946G>C[p.D4316H])in family 1 and another compound heterozygous mutation(DNAH10:c.8849G>A[p.G2950D];c.11509C>T[p.R3687W])in family 2.All the identified variants are absent or rare in public genome databases and are predicted to have deleterious effects according to multiple bioinformatic tools.Sanger sequencing revealed that these variants follow an autosomal recessive mode of inheritance.Hematoxylin and eosin(H&E)staining revealed MMAF,including sperm head abnormalities,in the patients.In addition,immunofluorescence staining revealed loss of DNAH10 protein signals along sperm flagella.These findings broaden the spectrum of DNAH10 variants and expand understanding of the genetic basis of male infertility associated with the MMAF phenotype.
文摘In recent years, social research surrounding the consequences of infertility has increasingly focused on the male perspective;however, a gap exists in the understanding of men’s experiences of male infertility treatment. This review aims to synthesize theexisting evidence concerning the psychological, social, and sexual burden of male infertility treatment on men, as well as patientneeds during clinical care. A systematic search identified 12 studies that are diverse in design, setting, and methods. Psychologicalevaluations have found that urological surgery may have a lasting impact on infertility-specific stress, and treatment failure canlead to feelings of depression, grief, and inadequacy. Men tended to have an avoidant coping mechanism throughout fertilitytreatment, and their self-esteem, relationship quality, and sexual functions can be tied to outcomes of treatment. Partner bonds canbe strengthened by mutual support and enhanced communication;couple separation, however, has been noted as a predominantreason for discontinuing male infertility treatment and may be associated with difficult circumstances surrounding severe maleinfertility. Surgical treatments can affect the sexual functioning of infertile men;however, the impact of testicular sperm extractionoutcomes appears to be psychologically driven whereas the improvements after microsurgical varicocelectomy are only evident inhypogonadal men. Clinically, there is a need for better inclusion, communication, education, and resource provision, to addressreported issues of marginalization and uncertainty in men. Routine psychosocial screening in cases of severe male infertility andfollow-up in cases of surgical treatment failure are likely beneficial.
文摘Infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family. Despite this, the molecular and genetic factors underlying the cause of infertility remain largely undiscovered. Nevertheless, more and more genetic factors associated with infertility are being identified. This review will focus on our current understanding of the chromosomal basis of male infertility specifically： chromosomal aneuploidy, structural and numerical karyotype abnormalities and Y chromosomal microdeletions. Chromosomal aneuploidy is the leading cause of pregnancy loss and developmental disabilities in humans. Aneuploidy is predominantly maternal in origin, but concerns have been raised regarding the safety of intracytoplasmic sperm injection as infertile men have significantly higher levels of sperm aneuploidy compared to their fertile counterparts. Males with numerical or structural karyotype abnormalities are also at an increased risk of producing aneuploid sperm. Our current understanding of how sperm aneuploidy translates to embryo aneuploidy will be reviewed, as well as the application of preimplantation genetic diagnosis （PGD） in such cases. Clinical recommendations where possible will be made, as well as discussion of the use of emerging array technology in PGD and its potential applications in male infertility.
文摘While we may be comfortable with an allopathic approach to male infertility, we are also responsible for knowledge about lifestyle modifications and holistic, complementary, and alternative therapies that are used by many of our patients. This paper provides an evidence-based review separating fact from fiction for several of these therapies. There is sufficient literature to support weight reduction by diet and exercise, smoking cessation, and alcohol moderation. Supplements that have demonstrated positive effects on male fertility on small randomized controlled trial （RCT） include aescin, coenzyme Qlo, glutathione, Korean red ginseng, L-carnitine, nigella sativa, omega-3, selenium, a combination of zinc and folate, and the Menevit antioxidant. There is no support for the use of Vitamin C, Vitamin E, or saffron. The data for Chinese herbal medications, acupuncture, mind-body practice, scrotal cooling, and faith-based healing are sparse or inconclusive.
文摘Human papillomavirus （HPV） is one of the most common sexually transmitted diseases which comprises a group of small DNA viruses that infect both cutaneous and mucous squamous epithelia. Liquid bead microarray technology （LBMA） were used to evaluate 24 HPV genotypes in confirmed fertile and infertile males of North China so that the effects of HPV infection on semen parameters and relationship with male infertility could be discussed. A total of 1138 subjects were recruited in this study; 142 were HPV-positive （12.48%）. Among 523 confirmed fertile males, only 35 were HPV-positive （6.70%）, and two of them had multiple infections. Among 615 infertile males, 107 were HPV-positive （17.4%）, and 29 of them had multiple infections. Infertile males had a relatively high HPV infection rate compared with confirmed fertile males. Sperm progressive motility （PR） and the normal morphology rate were significantly decreased in HPV-positive subjects. HPV-45, HPV-52, HPV-18, HPV-59 and HPV-16 infections were more frequently in infertile males. Hence, HPV infection is closely related to male infertility which will decrease sperm PR and morphology. HPV-45, HPV-52, HPV-18, HPV-59 and HPV-16 infection seems to be major risk factors.
基金ACKNOWLEDGMENTS This research was supported by the Major State Basic Research Development Program of China （973 Program, Noso 2006GB504005 and 2009CB941700）, the National Natural Science Foundation of China （No. 30872765） and the Basic Research Key Program of Shanghai （10]C1410800）. Shi-Wei Duan is sponsored partly by the K. C. Wong Magna Fund of Ningbo University. Wethank Dr Ching-Ling Chen for kind suggestions regarding English in drafting this paper.
文摘Multiplex polymerase chain reaction （PCR） has been widely used to detect Y-chromosome micredeletions, which is one of the major causes of male infertility. Both the European Academy of Andrology （EAA） and the European Molecular Genetics Quality Network （EMQN） have recommended the use of sY84 and sY86 markers for the detection of azoospermia factor a （AZFa） microdeletion during DNA testing for male infertility. In this study, a large-scale analysis of AZF microdeletion in a total of 630 Chinese males, including healthy semen donors （n=200）, infertile males with normal sperm count （n=226） and patients with either nonobstructive azoospermia or severe oligozoospermia （n=204）, was performed. A series of nine sequence-tagged site （STS） markers from the AZF region of the Y chromosome was used to detect microdeletions. All primers were designed based on the recommendations of the National Center for Biotechnology Information. An unusually high incidence （73/630, 11.6%） of sY84-absent but sY86-present genotypes was observed in the AZFa microdeletion screening. Sequencing the sY84-flanking region revealed a total of 73 patients with sY84-absent but sY86-present genotypes have a T-to-G transversion at the fifth base from the 5＇ end of the reverse sY84 primer. These prevalent false positives, which were not only observed in infertile men, but also observed in donors, resulted from a single-nucleotide polymorphism （SNP） named rs72609647 in the targeting sequence of the reverse sY84 primer. Our study suggests that a pre-screening of existence of rs72609647 polymorphism can prevent the frequent false positive results of AZFa microdeletions detection in the infertile Chinese males. Given the SNP rs72609647 was recently found in a deep sequencing of a Chinese individual, the current EAA and EMQN standards may need to be scrutinized among different populations to avoid the potential genetic variations in the primer binding sequences.
文摘The Y chromosome evolves from an autochromosome and accumulates male-related genes including sex-determining region of Y-chromosome （SRY） and several spermatogenesis-related genes. The human Y chromosome （60 Mb long） is largely composed of repetitive sequences that give it a heterochromatic appearance, and it consists of pseudoautosomal, euchromatic, and heterochromatic regions. Located on the two extremities of the Y chromosome, pseudoautosomal regions 1 and 2 （PAR1 and PAR2, 2.6 Mb and 320 bp long, respectively） are homologs with the termini of the X chromosome. The euchromatic region and some of the repeat-rich heterochromatic parts of the Y chromosome are called ＂male-specific Y＂ （MSY）, which occupy more than 95% of the whole Y chromosome. After evolution, the Y chromosome becomes the smallest in size with the least number of genes but with the most number of copies of genes that are mostly spermatogenesis-related. The Y chromosome is characterized by highly repetitive sequences （including direct repeats, inverted repeats, and palindromes） and high polymorphism. Several gene rearrangements on the Y chromosome occur during evolution owing to its specific gene structure. The consequences of such rearrangements are not only loss but also gain of specific genes. One hundred and fifty three haplotypes have been discovered in the human Y chromosome. The structure of the Y chromosome in the GenBank belongs to haplotype R1. There are 220 genes （104 coding genes, 111 pseudogenes, and 5 other uncategorized genes） according to the most recent count. The 104 coding genes encode a total of about 48 proteins/protein families （including putative proteins/protein families）. Among them, 16 gene products have been discovered in the azoospermia factor region （AZF） and are related to spermatogenesis. It has been discovered that one subset of gene rearrangements on the Y chromosome, ＂micro-deletions＂, is a major cause of male infertility in some populations. However, controversies exist about different Y chromosome haplotypes. Six AZFs of the Y chromosome have been discovered including AZFa, AZFb, AZFc, and their combinations AZFbc, AZFabc, and partial AZFc called AZFc/gr/gr. Different deletions in AZF lead to different content spermatogenesis loss from teratozoospermia to infertility in different populations depending on their Y haplotypes. This article describes the structure of the human Y chromosome and investigates the causes of micro-deletions and their relationship with male infertility from the view of chromosome evolution. After analysis of the relationship between AZFc and male infertility, we concluded that spermatogenesis is controlled by a network of genes, which may locate on the Y chromosome, the autochromosomes, or even on the X chromosome. Further investigation of the molecular mechanisms underlying male fertility/infertility will facilitate our knowledge of functional genomics.
文摘<abstract>During spermiogenesis, the protamine proteins play an integral role in spermatid chromatin compaction. Recent research has focused on many facets of protamine biology, including protamine gene and protein structure/ function relationships, mechanisms of protamine expression regulation and involvement of the protamines in male fertility. In this paper, we review our current understanding of the structure and function of the protamine-1 (P1) and protamine-2 (P2) proteins and genes, the expression and regulation of these genes and the relationship between the protamines and male fertility. In addition, we offer a brief outlook on future investigation into protamine proteins.
文摘Excessive amounts of reactive oxygen species （ROS） cause a state of oxidative stress, which result in sperm membrane lipid peroxidation, DNA damage and apoptosis, leading to decreased sperm viability and motility. Elevated levels of ROS are a major cause of idiopathic male factor infertility, which is an increasingly common problem today. Lycopene, the most potent singlet oxygen quencher of all carotenoids, is a possible treatment option for male infertility because of its antioxidant properties. By reacting with and neutralizing free radicals, lycopene could reduce the incidence of oxidative stress and thus, lessen the damage that would otherwise be inflicted on spermatozoa. It is postulated that lycopene may have other beneficial effects via nonoxidative mechanisms in the testis, such as gap junction communication, modulation of gene expression, regulation of the cell cycle and immunoenhancement. Various lycopene supplementation studies conducted on both humans and animals have shown promising results in alleviating male infertility--lipid peroxidation and DNA damage were decreased, while sperm count and viability, and general immunity were increased. Improvement of these parameters indicates a reduction in oxidative stress, and thus the spermatozoa is less vulnerable to oxidative damage, which increases the chances of a normal sperm fertilizing the egg. Human trials have reported improvement in sperm parameters and pregnancy rates with supplementation of 4-8 mg of lycopene daily for 3-12 months. However, further detailed and extensive research is still required to determine the dosage and the usefulness of lycopene as a treatment for male infertility.
文摘Male factor contributes to 50%-60% of overall infertility but is solely responsible in only 20% of couples. Although most male factor infertility is ascertained from an abnormal semen analysis, other male factors can be contributory especially if the sample returns normal. Male infertility can be due to identifiable hormonal or anatomical etiologies that may be reversible or irreversible. This manuscript will highlight existing guidelines and our recommendations for hormone evaluation for male infertility and empiric therapies including multivitamins, estrogen receptor modulators （clomiphene）, estrogen conversion blockers （anastrozole）, and hormone replacement.
