Objective Selective estrogen receptor modulators(SERMs)have demonstrated efficacy in the treatment of hypogonadism in males and male factor infertility.Two SERMs,clomiphene citrate and tamoxifen,are now prescribed for...Objective Selective estrogen receptor modulators(SERMs)have demonstrated efficacy in the treatment of hypogonadism in males and male factor infertility.Two SERMs,clomiphene citrate and tamoxifen,are now prescribed for off-label use to treat both conditions in males.However,existing literature compares mixed protocols with active management.We aimed to conduct a meta-analysis to evaluate the effect of clomiphene and tamoxifen versus placebo on natural pregnancy rates.Methods We conducted a comprehensive systematic review of electronic databases:MEDLINE,PubMed/PMC,EMBASE,CINAHL,Cochrane Central Register of Controlled Trials(CENTRAL),Scopus,Google Scholar,and Web of Science.Articles satisfying all selection criteria were analyzed.The primary outcome was the incidence of pregnancy after receiving the treatment.Secondary outcomes included serum follicle-stimulating hormone,luteinizing hormone,and testosterone levels,and sperm count and motility.We calculated the pooled odds ratio,risk ratio,and risk difference to ascertain possible alterations in the direction of the pooled effect size.Results Ten randomized controlled trials were ultimately included and underwent data extraction.Clomiphene citrate and placebo groups had similar pregnancy rates(10.4%and 7.1%,respectively;odds ratio 1.30[95%confidence interval 0.27–6.17];p=0.74).No meta-analysis could be calculated for pregnancy rates in tamoxifen versus placebo groups.Heterogeneity among the studies of both SERMs ranged from low to high.Conclusion Although clomiphene citrate and tamoxifen are often used off-label for the treatment of male infertility secondary to hypogonadism,studies of SERMs in the treatment of idiopathic male factor infertility are limited and heterogenous,preventing this meta-analysis from investigating the efficacy of SERMs on male infertility.The effect of clomiphene citrate or tamoxifen on the pregnancy rate remains uncertain.展开更多
Compounds isolated from Epimedium include the total flavonoids of Epimedium,icariin,and its metabolites(icaritin,icariside Ⅰ,and icariside Ⅱ),which have similar molecular structures.Modern pharmacological research a...Compounds isolated from Epimedium include the total flavonoids of Epimedium,icariin,and its metabolites(icaritin,icariside Ⅰ,and icariside Ⅱ),which have similar molecular structures.Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects,especially in improving sexual function,hormone regulation,anti-osteoporosis,immune function regulation,anti-oxidation,and anti-tumor activity.To date,we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system.However,their actions in other tissues have been reviewed in recent years.This review critically focuses on the Epimedium,its bioactive compounds,and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system.Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.展开更多
Mutations and rearrangements of mitochondrial genes cause plant cytoplasmic male sterility. It is a significant way to utilize hybrid vigor to enhance crop yield. Ogu cytoplasmic male sterility(CMS) is a natural cytop...Mutations and rearrangements of mitochondrial genes cause plant cytoplasmic male sterility. It is a significant way to utilize hybrid vigor to enhance crop yield. Ogu cytoplasmic male sterility(CMS) is a natural cytoplasmic male sterility type discovered in radishes, being successfully transferred to rapeseed and cruciferous vegetables. However, current studies lack depth in exploring the molecular mechanisms of its male sterility. This study confirmed that orf138 is the causal gene for Ogu CMS through the genetic transformation in Arabidopsis. Transcriptome analysis of aborted anthers in different stages suggested that differentially expressed genes(DEGs) are mainly enriched in pathways such as glycerophospholipid metabolism and arginine and proline metabolism. It reveals that key genes involved in lipid metabolism pathways are significantly down-regulated in the sterile line(OguA), including BnaGPAT1, localized within the tapetum mitochondrial and endoplasmic reticulum. This could lead to changes in the metabolism of substances like acylglycerols within the tapetum, causing disruptions in lipid metabolism. This is consistent with morphological and subcellular structural changes in the tapetum and microspore cells, as observed in the transmission electron microscopy. This abnormal lipid metabolism may trigger specific reactive oxygen species(ROS) accumulation in an oxidative stress response, ultimately leading to an aborted microspore. Our study based on transcriptome has deepened our understanding of the molecular mechanisms in Ogu CMS.展开更多
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
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(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
As a prerequisite for sexual reproduction,gametophyte development is an interesting process involving cell proliferation,differentiation and specialization.Gametogenesis has been extensively explored in model plants,b...As a prerequisite for sexual reproduction,gametophyte development is an interesting process involving cell proliferation,differentiation and specialization.Gametogenesis has been extensively explored in model plants,but the regulatory mechanism of gametophyte development largely remains unknown in Cucurbitaceae species.In present study,we have shown that watermelon ClBBM and ClPLT2,two AP2/ERF transcription factors,participated in both male and female gametophyte development.Clbbm and Clplt2 single mutants resembled wild-type phenotypes in both vegetative and reproductive development.But Clbbm/Clplt2 double mutant showed partial pollen abortion and bore less seeds comparing to WT.Our results indicated that the abnormal pollen grains were caused by premature tapetum degeneration,and reduced seed-set was due to faulty embryo sac development.ClBBM and ClPLT2 were expressed in FG4 embryo sacs,and their transcripts were also detectable in the tapetum and microspore of stage 9 anthers,which was consistent with developmental stages of defective phenotypes observed in double mutant.The expression of genes essential for tapetum development,ClATM1,ClAMS,ClMS1 and ClMS188,was decreased in Clbbm/Clplt2 double mutants.Moreover,the transcriptome analysis indicated that ClBBM and ClPLT2 participated in tapetum and pollen wall development by regulate cell cycle,transmembrane transport,glucan and cellulose metabolic process.Collectively,ClBBM and ClPLT2 were functionally redundant in regulating gametophyte development in watermelon,and their functions differ from their homologous genes in model plant Arabidopsis.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
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
Objective:To evaluate the antioxidant activity of Kaempferia(K.)parviflora rhizome extract and study its protective effect against male reproductive impairment induced by fenitrothion.Methods:The phytochemicals and an...Objective:To evaluate the antioxidant activity of Kaempferia(K.)parviflora rhizome extract and study its protective effect against male reproductive impairment induced by fenitrothion.Methods:The phytochemicals and antioxidant properties of K.parviflora ethanolic extract were assessed.Twenty-four male mice aged 4-weeks-old were assigned into four groups.Groups 1 to 4 respectively received extra virgin olive oil(served as the vehicle control),20 mg/kg body weight(bw)of fenitrothion,50 mg/kg bw of K.parviflora ethanolic extract,and 50 mg/kg bw of K.parviflora ethanolic extract plus 20 mg/kg bw of fenitrothion.Upon completion of 28 days of continuous feeding treatment,the mice were subjected to mating evaluation and the assessment of epididymal sperm quality,lipid peroxidation,testosterone level and histological evaluation.Results:Eight phytochemical compounds were detected in the ethanolic extract of K.parviflora via GC-MS.The extract exhibited a DPPH radical scavenging activity with an EC50 value of(0.870±0.007)mg/mL.Mice fed with fenitrothion in group 2 displayed an increase in relative testis weight,lipid peroxidation levels and a significant reduction in all sperm parameters(sperm concentration,progressive motility,and viability),as well as serum testosterone levels compared to the control mice in group 1(P<0.05).On the other hand,mice fed with K.parviflora ethanolic extract in group 3 showed a significant increase in serum testosterone levels compared to group 1.Mice co-administered with K.parviflora ethanolic extract and fenitrothion in group 4 exhibited a significant improvement in testosterone levels,sperm concentration,motility,and viability compared to the mice administered only with fenitrothion in group 2(P<0.05).Histological analysis of testicular tissue from group 4 further revealed improved testicular morphology in comparison to fenitrothion-treated mice.Conclusions:Eight bioactive compounds were identified in K.parviflora ethanolic extract and the extract exhibited antioxidative properties.Fenitrothion administration impairs testicular function,reducing sperm parameters and testosterone while increasing lipid peroxidation.However,K.parviflora ethanolic extract coadministration alleviates oxidative stress,improves sperm parameters and testosterone levels,and enhances testicular morphology.These findings suggest that K.parviflora ethanolic extract has the therapeutic potential in mitigating male reproductive adverse effects induced by fenitrothion.展开更多
Objective:To explore the associations between income levels,employment risk,lifestyles,occupational stress,and male fertility.Methods:This cross-sectional study analyzed 294 men seeking fertility treatment at fertilit...Objective:To explore the associations between income levels,employment risk,lifestyles,occupational stress,and male fertility.Methods:This cross-sectional study analyzed 294 men seeking fertility treatment at fertility clinics in Terengganu,Pahang,and Kuala Lumpur from November 2021 to June 2023.Data were collected through structured questionnaires covering income levels,lifestyles,employment risks,occupational stress,and semen quality.Multinomial logistic regression was employed to assess predictors of semen quality,with crude and adjusted odds ratios(OR)reported.Results:The lower-income group exhibited higher odds of having abnormal semen quality compared to normal semen quality.Specifically,these participants were more likely to experience azoospermia[crude OR 6.68,95%confidence interval(CI)1.84-52.63;adjusted OR 6.26,95%CI 1.76-51.38],indicating a link between low income and infertility issues.Lifestyle factors did not show significant associations with semen abnormalities after adjustment.High employment risks had significant associations with oligozoospermia after adjustment(crude OR 5.50,95%CI 2.14-14.11;adjusted OR 5.15,95%CI 1.93-13.71),while high occupational stress was linked to asthenozoospermia(crude OR 2.26,95%CI 1.09-4.68;adjusted OR 2.25,95%CI 1.07-4.69).Conclusions:The findings underscore the influence of socioeconomic and occupational factors on male fertility,showing associations between lower income levels,high-risk occupations,and semen abnormalities.In contrast,lifestyle factors did not show significant associations with semen abnormalities after adjustment.Nevertheless,the current findings should be further confirmed through more extensive studies focusing on abnormal semen and lifestyle factors.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
Spermiogenesis is an indispensable process occurring during the later stages of spermatogenesis.Despite multiple proteins being associated with spermiogenesis,the molecular mechanisms that control spermiogenesis remai...Spermiogenesis is an indispensable process occurring during the later stages of spermatogenesis.Despite multiple proteins being associated with spermiogenesis,the molecular mechanisms that control spermiogenesis remain poorly characterized.In this study,we show that 1700030J22Rik is exclusively expressed in testes of mice and investigate its roles in spermiogenesis using genetic and proteomic approaches.The deficiency in 1700030J22Rik in male mice results in severe subfertility,characterized by a substantial decrease in sperm concentration,motility,and abnormalities in the flagella.Furthermore,1700030J22RIK interacts with the A-kinase-anchoring protein AKAP3,and 1700030J22Rik knockout decreases AKAP3 and AKAP4 protein levels.Additionally,the absence of 1700030J22RIK alters spermatozoal levels of the subunits of protein kinase A,leading to reduced protein phosphorylation and impaired sperm motility.This study reveals that 1700030J22Rik plays a crucial role in the organization of sperm morphology and function in mice.展开更多
Background:Obesity represents a major public health issue,closely linked to a range of metabolic and reproductive disorders.Electroacupuncture(EA)has emerged as a potential non-pharmacological intervention that may al...Background:Obesity represents a major public health issue,closely linked to a range of metabolic and reproductive disorders.Electroacupuncture(EA)has emerged as a potential non-pharmacological intervention that may alleviate complications associated with obesity,including reproductive dysfunction.Objectives:This study sought to evaluate the impact of EA on leptin/kisspeptin signaling pathways and hypothalamic inflammation in obese male rats,with the aim of elucidating its potential mechanisms in mitigating reproductive disorders related to obesity.Methods:Forty male Wistar rats were allocated into two groups:a regular diet(RD,n=10)group and a high-fat diet(HFD,n=30)group.Following an 8-week period,23 out of the 30 rats in the HFD group satisfied the criteria for the obesity model,characterized by a body weight surpassing 20%of the average body weight of the RD group.From these 23 obese rats,20 were randomly selected and further subdivided into the Model(n=10)and EA(n=10)groups.The EA group underwent EA treatment at the Zusanli(ST36),Shenshu(BL23),and Sanyinjiao(SP6)acupoints over a duration of 4 weeks.The study assessed parameters including body weight,serum lipid levels,reproductive hormone levels,hypothalamic histology,inflammation markers,and neurotransmitter levels.Results:EA treatment significantly reduced body weight,improved lipid profiles,and restored hormone levels towards those seen in control animals.Histological analysis showed improved neuronal integrity and a shift in microglial polarization towards an anti-inflammatory phenotype in the EA group.EA treatment was associated with improvements in leptin and kisspeptin signaling activity,which may contribute to its beneficial effects on reproductive function in obese male rats.Neurotransmitter profiling and untargeted serum metabolomics revealed significant improvements in metabolic pathways related to amino acid and lipid metabolism,including key pathways associated with dopamine,serotonin,and glutamine.Conclusions:EA significantly alleviated obesity-induced reproductive dysfunction by modulating leptin and kisspeptin signaling,reducing hypothalamic inflammation,and improving neurotransmitter and serum metabolic profiles,suggesting its potential as a therapeutic strategy for reproductive issues related to obesity.Additional research is essential to investigate the molecular pathways of EA and assess its clinical applicability.展开更多
Honglian type-cytoplasmic male sterility(HL-CMS)is caused by the inter-communication between the nucleus and mitochondria.However,the mechanisms by which sterility genes regulate metabolic alterations and changes in m...Honglian type-cytoplasmic male sterility(HL-CMS)is caused by the inter-communication between the nucleus and mitochondria.However,the mechanisms by which sterility genes regulate metabolic alterations and changes in mitochondrial morphology in the pollen of HL-CMS remain unclear.In this study,we compared the morphological differences between the pollen of the male sterile line YA and the near-isogenic line NIL-Rf6 using hematoxylin-eosin staining and 4ʹ,6-diamidino-2-phenylindole(DAPI)staining.HL-CMS is characterized by gametophytic sterility,where the aborted pollen grains are empty,and the tapetal layer remains intact.Transmission electron microscopy was employed to observe mitochondrial morphological changes at the microspore stage,revealing significant mitochondrial alterations,characterized by the formation of'large spherical mitochondria',occurred at the binucleate stage in the YA line.Additionally,metabolomics analysis revealed decreased levels of metabolites associated with the carbohydrate and flavonoid pathways.Notably,the decrease in flavonoids was found to contribute to an elevation in reactive oxygen species(ROS)levels.Therefore,we propose a model in which rice fertility is modulated by the levels of pollen carbohydrates and flavonoid metabolites,with impaired mitochondrial energy production and reduced flavonoid biosynthesis as the main causes of ROS accumulation and pollen abortion in rice.展开更多
Exploring the phenotypic trait variation and diversity of kiwifruit male plant resources can support selection,breeding,and genetic improvement,ultimately enhancing agricultural production.In this study,50 kiwifruit m...Exploring the phenotypic trait variation and diversity of kiwifruit male plant resources can support selection,breeding,and genetic improvement,ultimately enhancing agricultural production.In this study,50 kiwifruit male plants were collected from the resource nursery of Sichuan Provincial Natural Resources Bureau.The phenotypic variation of the germplasm was analyzed using 16 quantitative traits.The analysis involved coefficient of variation(CV),Shannon-Wiener index(H),principal component analysis,correlation analysis,cluster analysis,and comprehensive evaluation.The results showed that the variation range of 16 phenotypic traits in kiwifruit male germplasm resources was 1.55%to 83.71%,with an average coefficient of variation of 28.62%,and an H index of 1.265 to 2.941.The average CVs of diploid,tetraploid,and hexaploid were 22.62%,18.99%and 18.18%,respectively,and the average CV of diploid was the largest.Indicated that the male germplasm resources of kiwifruit showed significant phenotypic diversity,and the diploid showed higher diversity characteristics.Principal component analysis(PCA)revealed that the cumulative variance contribution rate of the first seven principal components was 76.66%,which effectively captured the information from 21 traits.Cluster analysis divided the 50 kiwifruit male germplasm resources into 4 clusters;each cluster exhibited distinct phenotypic characteristics.The analysis also determined the trait characteristics and breeding value of each cluster.The results of this study provide valuable information for genetic improvement,protection,and evaluation of kiwifruit male germplasm resources.展开更多
The circadian clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms.Testosterone,as one of the most critical sex hormones,is essential for th...The circadian clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms.Testosterone,as one of the most critical sex hormones,is essential for the development of the reproductive system,maintenance of reproductive function,and the overall health of males.The secretion of testosterone in mammals is characterized by distinct circadian rhythms and is closely associated with the regulation of circadian clock genes.Here we review the central and peripheral regulatory mechanisms underlying the influence of circadian clock genes upon testosterone synthesis.We also examined the specific effects of these genes on the occurrence,development,and treatment of common male diseases,including late-onset hypogonadism,erectile dysfunction,male infertility,and prostate cancer.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
文摘Objective Selective estrogen receptor modulators(SERMs)have demonstrated efficacy in the treatment of hypogonadism in males and male factor infertility.Two SERMs,clomiphene citrate and tamoxifen,are now prescribed for off-label use to treat both conditions in males.However,existing literature compares mixed protocols with active management.We aimed to conduct a meta-analysis to evaluate the effect of clomiphene and tamoxifen versus placebo on natural pregnancy rates.Methods We conducted a comprehensive systematic review of electronic databases:MEDLINE,PubMed/PMC,EMBASE,CINAHL,Cochrane Central Register of Controlled Trials(CENTRAL),Scopus,Google Scholar,and Web of Science.Articles satisfying all selection criteria were analyzed.The primary outcome was the incidence of pregnancy after receiving the treatment.Secondary outcomes included serum follicle-stimulating hormone,luteinizing hormone,and testosterone levels,and sperm count and motility.We calculated the pooled odds ratio,risk ratio,and risk difference to ascertain possible alterations in the direction of the pooled effect size.Results Ten randomized controlled trials were ultimately included and underwent data extraction.Clomiphene citrate and placebo groups had similar pregnancy rates(10.4%and 7.1%,respectively;odds ratio 1.30[95%confidence interval 0.27–6.17];p=0.74).No meta-analysis could be calculated for pregnancy rates in tamoxifen versus placebo groups.Heterogeneity among the studies of both SERMs ranged from low to high.Conclusion Although clomiphene citrate and tamoxifen are often used off-label for the treatment of male infertility secondary to hypogonadism,studies of SERMs in the treatment of idiopathic male factor infertility are limited and heterogenous,preventing this meta-analysis from investigating the efficacy of SERMs on male infertility.The effect of clomiphene citrate or tamoxifen on the pregnancy rate remains uncertain.
基金supported by the National Nature Science Foundation of China(NSFC,No.31960156,No.31660338,No.31760627,and No.32270848)Collaborative Innovation Center of Chinese Ministry of Education(2020-39),Science and Technology Support Program of Guizhou Province(QKH[2021]111,QKH[2020]4Y192,QKH[2018]5772-006,and QKH[2019]5406)Science and Technology Fund of Guizhou Provincial Health Commission(gzwkj2022-019).
文摘Compounds isolated from Epimedium include the total flavonoids of Epimedium,icariin,and its metabolites(icaritin,icariside Ⅰ,and icariside Ⅱ),which have similar molecular structures.Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects,especially in improving sexual function,hormone regulation,anti-osteoporosis,immune function regulation,anti-oxidation,and anti-tumor activity.To date,we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system.However,their actions in other tissues have been reviewed in recent years.This review critically focuses on the Epimedium,its bioactive compounds,and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system.Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
基金supported by the National Natural Science Foundation of China (31930032)。
文摘Mutations and rearrangements of mitochondrial genes cause plant cytoplasmic male sterility. It is a significant way to utilize hybrid vigor to enhance crop yield. Ogu cytoplasmic male sterility(CMS) is a natural cytoplasmic male sterility type discovered in radishes, being successfully transferred to rapeseed and cruciferous vegetables. However, current studies lack depth in exploring the molecular mechanisms of its male sterility. This study confirmed that orf138 is the causal gene for Ogu CMS through the genetic transformation in Arabidopsis. Transcriptome analysis of aborted anthers in different stages suggested that differentially expressed genes(DEGs) are mainly enriched in pathways such as glycerophospholipid metabolism and arginine and proline metabolism. It reveals that key genes involved in lipid metabolism pathways are significantly down-regulated in the sterile line(OguA), including BnaGPAT1, localized within the tapetum mitochondrial and endoplasmic reticulum. This could lead to changes in the metabolism of substances like acylglycerols within the tapetum, causing disruptions in lipid metabolism. This is consistent with morphological and subcellular structural changes in the tapetum and microspore cells, as observed in the transmission electron microscopy. This abnormal lipid metabolism may trigger specific reactive oxygen species(ROS) accumulation in an oxidative stress response, ultimately leading to an aborted microspore. Our study based on transcriptome has deepened our understanding of the molecular mechanisms in Ogu CMS.
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.
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.
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 Youth Talent Program(Grant No.A279021801)Key-Area R&D Program of Guangdong Province(Grant No.2022B0202060001)+3 种基金Science and Technology Innovation Team of Shaanxi(Grant No.2021TD-32)the Natural Science Foundation of Shaanxi Province(Grant Nos.2021JM-089,2022JM112 and 2022JQ-162)the Key R&D Project from Yangling Seed Industry Innovation Center(Grant No.K3031322016)Fundamental Research Funds for the Central Universities(Grant No.2452022111)。
文摘As a prerequisite for sexual reproduction,gametophyte development is an interesting process involving cell proliferation,differentiation and specialization.Gametogenesis has been extensively explored in model plants,but the regulatory mechanism of gametophyte development largely remains unknown in Cucurbitaceae species.In present study,we have shown that watermelon ClBBM and ClPLT2,two AP2/ERF transcription factors,participated in both male and female gametophyte development.Clbbm and Clplt2 single mutants resembled wild-type phenotypes in both vegetative and reproductive development.But Clbbm/Clplt2 double mutant showed partial pollen abortion and bore less seeds comparing to WT.Our results indicated that the abnormal pollen grains were caused by premature tapetum degeneration,and reduced seed-set was due to faulty embryo sac development.ClBBM and ClPLT2 were expressed in FG4 embryo sacs,and their transcripts were also detectable in the tapetum and microspore of stage 9 anthers,which was consistent with developmental stages of defective phenotypes observed in double mutant.The expression of genes essential for tapetum development,ClATM1,ClAMS,ClMS1 and ClMS188,was decreased in Clbbm/Clplt2 double mutants.Moreover,the transcriptome analysis indicated that ClBBM and ClPLT2 participated in tapetum and pollen wall development by regulate cell cycle,transmembrane transport,glucan and cellulose metabolic process.Collectively,ClBBM and ClPLT2 were functionally redundant in regulating gametophyte development in watermelon,and their functions differ from their homologous genes in model plant Arabidopsis.
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.
基金supported by Universiti Tunku Abdul Rahman(UTAR)Research Fund(IPSR/RMC/UTARRF 2021-C2/40).
文摘Objective:To evaluate the antioxidant activity of Kaempferia(K.)parviflora rhizome extract and study its protective effect against male reproductive impairment induced by fenitrothion.Methods:The phytochemicals and antioxidant properties of K.parviflora ethanolic extract were assessed.Twenty-four male mice aged 4-weeks-old were assigned into four groups.Groups 1 to 4 respectively received extra virgin olive oil(served as the vehicle control),20 mg/kg body weight(bw)of fenitrothion,50 mg/kg bw of K.parviflora ethanolic extract,and 50 mg/kg bw of K.parviflora ethanolic extract plus 20 mg/kg bw of fenitrothion.Upon completion of 28 days of continuous feeding treatment,the mice were subjected to mating evaluation and the assessment of epididymal sperm quality,lipid peroxidation,testosterone level and histological evaluation.Results:Eight phytochemical compounds were detected in the ethanolic extract of K.parviflora via GC-MS.The extract exhibited a DPPH radical scavenging activity with an EC50 value of(0.870±0.007)mg/mL.Mice fed with fenitrothion in group 2 displayed an increase in relative testis weight,lipid peroxidation levels and a significant reduction in all sperm parameters(sperm concentration,progressive motility,and viability),as well as serum testosterone levels compared to the control mice in group 1(P<0.05).On the other hand,mice fed with K.parviflora ethanolic extract in group 3 showed a significant increase in serum testosterone levels compared to group 1.Mice co-administered with K.parviflora ethanolic extract and fenitrothion in group 4 exhibited a significant improvement in testosterone levels,sperm concentration,motility,and viability compared to the mice administered only with fenitrothion in group 2(P<0.05).Histological analysis of testicular tissue from group 4 further revealed improved testicular morphology in comparison to fenitrothion-treated mice.Conclusions:Eight bioactive compounds were identified in K.parviflora ethanolic extract and the extract exhibited antioxidative properties.Fenitrothion administration impairs testicular function,reducing sperm parameters and testosterone while increasing lipid peroxidation.However,K.parviflora ethanolic extract coadministration alleviates oxidative stress,improves sperm parameters and testosterone levels,and enhances testicular morphology.These findings suggest that K.parviflora ethanolic extract has the therapeutic potential in mitigating male reproductive adverse effects induced by fenitrothion.
基金supported by Malaysia's Ministry of Higher Education through the Fundamental Research Grant Scheme(FRGS)under the reference code FRGS/1/2020/SS0/UMT/02/3 and vote number 59637.
文摘Objective:To explore the associations between income levels,employment risk,lifestyles,occupational stress,and male fertility.Methods:This cross-sectional study analyzed 294 men seeking fertility treatment at fertility clinics in Terengganu,Pahang,and Kuala Lumpur from November 2021 to June 2023.Data were collected through structured questionnaires covering income levels,lifestyles,employment risks,occupational stress,and semen quality.Multinomial logistic regression was employed to assess predictors of semen quality,with crude and adjusted odds ratios(OR)reported.Results:The lower-income group exhibited higher odds of having abnormal semen quality compared to normal semen quality.Specifically,these participants were more likely to experience azoospermia[crude OR 6.68,95%confidence interval(CI)1.84-52.63;adjusted OR 6.26,95%CI 1.76-51.38],indicating a link between low income and infertility issues.Lifestyle factors did not show significant associations with semen abnormalities after adjustment.High employment risks had significant associations with oligozoospermia after adjustment(crude OR 5.50,95%CI 2.14-14.11;adjusted OR 5.15,95%CI 1.93-13.71),while high occupational stress was linked to asthenozoospermia(crude OR 2.26,95%CI 1.09-4.68;adjusted OR 2.25,95%CI 1.07-4.69).Conclusions:The findings underscore the influence of socioeconomic and occupational factors on male fertility,showing associations between lower income levels,high-risk occupations,and semen abnormalities.In contrast,lifestyle factors did not show significant associations with semen abnormalities after adjustment.Nevertheless,the current findings should be further confirmed through more extensive studies focusing on abnormal semen and lifestyle factors.
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.
基金supported by the National Key Research and Development Program of China(2024YFC2706800 to F.S.)the National Natural Science Foundation of China(U24A20657 F.S.)the Key Research and Development Program of Zhejiang Province(2023C03035 to F.S.).
文摘Spermiogenesis is an indispensable process occurring during the later stages of spermatogenesis.Despite multiple proteins being associated with spermiogenesis,the molecular mechanisms that control spermiogenesis remain poorly characterized.In this study,we show that 1700030J22Rik is exclusively expressed in testes of mice and investigate its roles in spermiogenesis using genetic and proteomic approaches.The deficiency in 1700030J22Rik in male mice results in severe subfertility,characterized by a substantial decrease in sperm concentration,motility,and abnormalities in the flagella.Furthermore,1700030J22RIK interacts with the A-kinase-anchoring protein AKAP3,and 1700030J22Rik knockout decreases AKAP3 and AKAP4 protein levels.Additionally,the absence of 1700030J22RIK alters spermatozoal levels of the subunits of protein kinase A,leading to reduced protein phosphorylation and impaired sperm motility.This study reveals that 1700030J22Rik plays a crucial role in the organization of sperm morphology and function in mice.
基金supported by the Natural Science Foundation of Sichuan Province(2023NSFSC1799)the Science and Technology Development Fund of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine(23YY07)National Natural Science Foundation of China(82405413).
文摘Background:Obesity represents a major public health issue,closely linked to a range of metabolic and reproductive disorders.Electroacupuncture(EA)has emerged as a potential non-pharmacological intervention that may alleviate complications associated with obesity,including reproductive dysfunction.Objectives:This study sought to evaluate the impact of EA on leptin/kisspeptin signaling pathways and hypothalamic inflammation in obese male rats,with the aim of elucidating its potential mechanisms in mitigating reproductive disorders related to obesity.Methods:Forty male Wistar rats were allocated into two groups:a regular diet(RD,n=10)group and a high-fat diet(HFD,n=30)group.Following an 8-week period,23 out of the 30 rats in the HFD group satisfied the criteria for the obesity model,characterized by a body weight surpassing 20%of the average body weight of the RD group.From these 23 obese rats,20 were randomly selected and further subdivided into the Model(n=10)and EA(n=10)groups.The EA group underwent EA treatment at the Zusanli(ST36),Shenshu(BL23),and Sanyinjiao(SP6)acupoints over a duration of 4 weeks.The study assessed parameters including body weight,serum lipid levels,reproductive hormone levels,hypothalamic histology,inflammation markers,and neurotransmitter levels.Results:EA treatment significantly reduced body weight,improved lipid profiles,and restored hormone levels towards those seen in control animals.Histological analysis showed improved neuronal integrity and a shift in microglial polarization towards an anti-inflammatory phenotype in the EA group.EA treatment was associated with improvements in leptin and kisspeptin signaling activity,which may contribute to its beneficial effects on reproductive function in obese male rats.Neurotransmitter profiling and untargeted serum metabolomics revealed significant improvements in metabolic pathways related to amino acid and lipid metabolism,including key pathways associated with dopamine,serotonin,and glutamine.Conclusions:EA significantly alleviated obesity-induced reproductive dysfunction by modulating leptin and kisspeptin signaling,reducing hypothalamic inflammation,and improving neurotransmitter and serum metabolic profiles,suggesting its potential as a therapeutic strategy for reproductive issues related to obesity.Additional research is essential to investigate the molecular pathways of EA and assess its clinical applicability.
基金supported by the National Natural Science Foundation of China(Grant No.32472185)the Key Research and Development Program of Hubei Province,China(Grant No.2022BFE003)the Hubei Agriculture Science and Technology Innovation Center program,and the National Rice Industry Technology System,China(Grant No.CARS-01-07).
文摘Honglian type-cytoplasmic male sterility(HL-CMS)is caused by the inter-communication between the nucleus and mitochondria.However,the mechanisms by which sterility genes regulate metabolic alterations and changes in mitochondrial morphology in the pollen of HL-CMS remain unclear.In this study,we compared the morphological differences between the pollen of the male sterile line YA and the near-isogenic line NIL-Rf6 using hematoxylin-eosin staining and 4ʹ,6-diamidino-2-phenylindole(DAPI)staining.HL-CMS is characterized by gametophytic sterility,where the aborted pollen grains are empty,and the tapetal layer remains intact.Transmission electron microscopy was employed to observe mitochondrial morphological changes at the microspore stage,revealing significant mitochondrial alterations,characterized by the formation of'large spherical mitochondria',occurred at the binucleate stage in the YA line.Additionally,metabolomics analysis revealed decreased levels of metabolites associated with the carbohydrate and flavonoid pathways.Notably,the decrease in flavonoids was found to contribute to an elevation in reactive oxygen species(ROS)levels.Therefore,we propose a model in which rice fertility is modulated by the levels of pollen carbohydrates and flavonoid metabolites,with impaired mitochondrial energy production and reduced flavonoid biosynthesis as the main causes of ROS accumulation and pollen abortion in rice.
基金funded by Sichuan Science and Technology Program(2023YFH0006).
文摘Exploring the phenotypic trait variation and diversity of kiwifruit male plant resources can support selection,breeding,and genetic improvement,ultimately enhancing agricultural production.In this study,50 kiwifruit male plants were collected from the resource nursery of Sichuan Provincial Natural Resources Bureau.The phenotypic variation of the germplasm was analyzed using 16 quantitative traits.The analysis involved coefficient of variation(CV),Shannon-Wiener index(H),principal component analysis,correlation analysis,cluster analysis,and comprehensive evaluation.The results showed that the variation range of 16 phenotypic traits in kiwifruit male germplasm resources was 1.55%to 83.71%,with an average coefficient of variation of 28.62%,and an H index of 1.265 to 2.941.The average CVs of diploid,tetraploid,and hexaploid were 22.62%,18.99%and 18.18%,respectively,and the average CV of diploid was the largest.Indicated that the male germplasm resources of kiwifruit showed significant phenotypic diversity,and the diploid showed higher diversity characteristics.Principal component analysis(PCA)revealed that the cumulative variance contribution rate of the first seven principal components was 76.66%,which effectively captured the information from 21 traits.Cluster analysis divided the 50 kiwifruit male germplasm resources into 4 clusters;each cluster exhibited distinct phenotypic characteristics.The analysis also determined the trait characteristics and breeding value of each cluster.The results of this study provide valuable information for genetic improvement,protection,and evaluation of kiwifruit male germplasm resources.
基金supported by grants from the National Natural Science Foundation of China(N0.82474525 and No.82074444)the Hunan Provincial Natural Outstanding Young People Science Foundation(2023JJ10032)the Hunan Province Health and High-Level Talent Medical Academic Leader Training Plan(20240304051).
文摘The circadian clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms.Testosterone,as one of the most critical sex hormones,is essential for the development of the reproductive system,maintenance of reproductive function,and the overall health of males.The secretion of testosterone in mammals is characterized by distinct circadian rhythms and is closely associated with the regulation of circadian clock genes.Here we review the central and peripheral regulatory mechanisms underlying the influence of circadian clock genes upon testosterone synthesis.We also examined the specific effects of these genes on the occurrence,development,and treatment of common male diseases,including late-onset hypogonadism,erectile dysfunction,male infertility,and prostate cancer.
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.
