Simulation can be defined as malingering, or sometimes functional visual loss (FVL). It manifests as either simulating an ophthalmic disease (positive simulation), or denial of ophthalmic disease (negative simulation)...Simulation can be defined as malingering, or sometimes functional visual loss (FVL). It manifests as either simulating an ophthalmic disease (positive simulation), or denial of ophthalmic disease (negative simulation). Conscious behavior and compensation or indemnity claims are prominent features of simulation. Since some authors suggest that this is a manifestation of underlying psychopathology, even conversion is included in this context. In today's world, every ophthalmologist can face with simulation of ophthalmic disease or disorder. In case of simulation suspect, the physician's responsibility is to prove the simulation considering the disease/disorder first, and simulation as an exclusion. In simulation examinations, the physician should be firm and smart to select appropriate test(s) to convince not only the subject, but also the judge in case of indemnity or compensation trials. Almost all ophthalmic sensory and motor functions including visual acuity, visual field, color vision and night vision can be the subject of simulation. Examiner must be skillful in selecting the most appropriate test. Apart from those in the literature, we included all kinds of simulation in ophthalmology. In addition, simulation examination techniques, such as, use of OCT (optical coherence tomography), frequency doubling perimetry (FDP), and modified polarization tests were also included. In this review, we made a thorough literature search, and added our experiences to give the readers up-to-date information on malingering or simulation in ophthalmology.展开更多
· Simulation can be defined as malingering, or sometimes functional visual loss (FVL). It manifests as either simulating an ophthalmic disease (positive simulation), or denial of ophthalmic disease (negative simu...· Simulation can be defined as malingering, or sometimes functional visual loss (FVL). It manifests as either simulating an ophthalmic disease (positive simulation), or denial of ophthalmic disease (negative simulation). Conscious behavior and compensation or indemnity claims are prominent features of simulation. Since some authors suggest that this is a manifestation of underlying psychopathology, even conversion is included in this context. In today’s world, every ophthalmologist can face with simulation of ophthalmic disease or disorder. In case of simulation suspect, the physician’s responsibility is to prove the simulation considering the disease/disorder first, and simulation as an exclusion. In simulation examinations, the physician should be firm and smart to select appropriate test (s) to convince not only the subject, but also the judge in case of indemnity or compensation trials. Almost all ophthalmic sensory and motor functions including visual acuity, visual field, color vision and night vision can be the subject of simulation. Examiner must be skillful in selecting the most appropriate test. Apart from those in the literature, we included all kinds of simulation in ophthalmology. In addition, simulation examination techniques, such as, use of optical coherence tomography, frequency doubling perimetry (FDP), and modified polarization tests were also included. In this review, we made a thorough literature search, and added our experiences to give the readers up -to -date information on malingering or simulation in ophthalmology. ·展开更多
The P300, an endogenous subcomponent of the event-related potential, is thought to reflect cognitive processes. The event-related potential evoked by the old-new memory recognition task in the oddball paradigm is suit...The P300, an endogenous subcomponent of the event-related potential, is thought to reflect cognitive processes. The event-related potential evoked by the old-new memory recognition task in the oddball paradigm is suitable for examining the neural processes involved in malingered neurocognitive deficits. Forty-four undergraduates were randomly assigned to a simulated malingering group and a truth-telling group, Another 22 patients with head injudes were enrolled as a control group. All participants completed the old-new memory recognition task in the oddball paradigm. The mean P300 amplitude of the simulated malingering group was significantly reduced compared with the truth-telling group （P 〈 0.01）, but was increased compared with the control group （P〈 0.01）. These results revealed that the P300, evoked by the old-new memory recognition task of the oddball paradigm, may be a helpful indicator for determining cognitive malingering.展开更多
The main high points ofthis tour are sightseeing inthe Maling River Valley, riftvalley drifting, a visit to theBouyei village, and theGuizhou Wedding CustomsMuseum.
Recent studies have shown that lipid metabolism is a key factor affecting anther development and male fertility.However,how plants regulating the metabolic balance of multiple lipids to ensure proper anther developmen...Recent studies have shown that lipid metabolism is a key factor affecting anther development and male fertility.However,how plants regulating the metabolic balance of multiple lipids to ensure proper anther development and male fertility remains unclear.Analyzing lipid molecules related to anther fertility and genes responsible for their biosynthesis is crucial for understanding the physiological significance of lipid metabolism in crop fertility.In this study,we compared the transcriptome and the composition and content of lipids in anthers of two upland cotton(Gossypium hirsutum) materials,Shida 98(WT) and its nearly-isogenic male sterile line Shida 98A(MS).Transcriptomics analysis identified many differentially expressed genes(DEGs) between the two materials,with the genes of the alpha-linolenic acid metabolism pathway being the most significantly associated with the male sterility phenotype.Investigations on lipids revealed that the MS anthers over-accumulated free fatty acids(FFAs),phosphatidic acid(PA),mono-and di-galactosyldiacylglycerol(MGDG and DGDG),and had a decreased content of triacylglycerol(TAG),which was closely related to the abnormal metabolism of alpha-linolenic acid(C18:3);therefore,the major lipids containing C18:3-acyl chains,such as PA,MGDG,DGDG,and TAG,are proposed to play a major role in cotton anther development.We also showed that an excessive level of MGDG and DGDG caused jasmonic acid(JA) overaccumulation in MS anthers,which in turn inhibited the expression of GhFAD3 and consequently reduced the C18:3 content,presumably via a feedback regulation mechanism,ultimately affecting plant fertility.Together,our results revealed the importance of a balanced lipid metabolism in regulating the development of cotton anther and pollen and consequently male fertility.展开更多
Mammalian fertilization involves the migration of spermatozoa through the female reproductive system.Early embryonic development is a consequence of several steps and signaling pathways being activated,as well as bioc...Mammalian fertilization involves the migration of spermatozoa through the female reproductive system.Early embryonic development is a consequence of several steps and signaling pathways being activated,as well as biochemical and morphological modifications of spermatozoa that enable them to penetrate the membrane of mature oocytes.There are some crucial steps known to clearly explain the process of fertilization,starting with hyperactivation of spermatozoa,mutual recognition,and binding of gametes mediated by receptors located on the surface membranes of both gametes.The final step is followed by oocyte activation,which is primarily triggered via sperm-derived factors,inducing a sharp increase in intracellular calcium levels,eventually leading to polyspermy block.This review integrates current knowledge of the molecular and physiological events governing fertilization,emphasizing how ion regulation and signaling pathways converge to enable sperm function and oocyte activation.Special attention is given to sperm-derived factors such as phospholipase C zeta(PLCζ)and post-acrosomal sheath WW domain-binding protein(PAWP),which play essential roles in triggering calcium release and supporting early embryonic development.展开更多
Objective:To investigate the sterilizing potential of zinc gluconate,calcium chloride(CaCl_(2))and cadmium chloride(CdCl_(2))following a single intratesticular administration in adult male rats.Methods:60 adult male W...Objective:To investigate the sterilizing potential of zinc gluconate,calcium chloride(CaCl_(2))and cadmium chloride(CdCl_(2))following a single intratesticular administration in adult male rats.Methods:60 adult male Wistar albino rats(Rattus norvegicus)weighing 160-200 g and aged 5-6 months randomly received a single intratesticular injection of normal saline(Group A),zinc gluconate 13.3 mg/mL plus L-Arginine(Group B),20%CaCl_(2)(Group C),and CdCl_(2)0.5 mg/kg body weight plus ethylenediaminetetraacetic acid(EDTA)(Group D),respectively,along the entire route from the caudoventral aspect of each testis.They were euthanized up to 180 days to evaluate reproductive tract toxicology.Results:The reproductive organ weights were markedly reduced,with testes severely atrophied in group B,pea-sized and stony hard in group C,and moderately reduced in group D.Azoospermia was evident in groups B and C,while sperm concentration was reduced to<1 million/mL with zero sperm motility in group D.Rats of groups B and C failed to show mounting and copulatory behaviour.A completely disorganized mesh of cellular elements was observed in the seminiferous tubules of group B,while pyknotic germ cell and arrest of spermatogenesis,exfoliated germ cells,occasional syncytial bodies and smaller Leydig cells were evident in groups C and D.Significantly reduced testosterone levels,increased luteinizing hormone(LH)and follicle-stimulating hormone(FSH)levels,returned to normal after 90 days in group D.Conclusions:Zinc gluconate and CaCl_(2)injections severely affected the reproductive organs and libido and rats treated with CdCl_(2)exhibited diminished spermatogenesis with normal libido.Thus,the need-based selection of intratesticular agents should consider their distinct effects on spermatogenesis,libido,and hormonal balance for achieving targeted sterilization outcomes.展开更多
Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor ...Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor receptor 2(HER2)-negative and estrogen receptor(ER)-positive,and lacks routine screening,leading to delayed diagnosis and advanced disease.Major risk factors include hormonal imbalance,radiation exposure,obesity,alcohol use,and Breast Cancer Gene 1 and 2(BRCA1/2)mutations.Clinically,it may resemble gynecomastia but usually appears as a unilateral,painless mass or nipple discharge.Advances in imaging and liquid biopsy have enhanced early detection.Molecular mechanisms involve hormonal signaling,HER2/epidermal growth factor receptor(EGFR)pathways,tumor suppressor gene alterations,and epigenetic changes.While standard treatments mirror those for female breast cancer,emerging options such as cyclin-dependent kinase 4 and 6(CDK4/6),and poly(ADP-ribose)polymerase(PARP)inhibitors,immunotherapy,and precision medicine are reshaping management.Incorporating artificial intelligence,molecular profiling,and male-specific clinical trials is essential to improve outcomes and bridge current diagnostic and therapeutic gaps.展开更多
Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to i...Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to its therapeutic properties,but its exact role and molecular mechanisms in treatment of reproductive dysfunction remain unclear.Methods:During this study,36 rats were randomly divided into six groups(n=6):control,CYP-induced(60 mg/kg),standard(leuprolide 3 mg/kg)and three treatment groups receiving aqueous,ethanolic,and oil extracts(50 mg/kg or 20 mL/kg)for post-toxicity induction.Results:The finding represented that exposure of CYP significantly increased oxidative stress,disrupted testicular architecture,and markedly reduced testosterone levels(P<0.05).Importantly,Crocus sativus L.treatment alleviated these changes by increasing the expression of Nrf2(nuclear factor erythroid 2-related factor 2),restoring the activity of antioxidant enzymes,and enhancing testicular histomorphology.Surprisingly,molecular docking established a high binding affinity of Crocus sativus L.phytoconstituents such as gallic acid,cinnamic acid and quercetin to the Nrf2-Keap1 complex.It is worth noting that,Crocus sativus L.exhibited a high level of protection against reproductive toxicity caused by CYP in male rats,which was mediated by the activation of Nrf2 pathway,reduction of oxidative damage,and favorable ADMET characteristics.Conclusion:Notably,this research provides a more valid,safe,and effective method of developing new drugs for reproductive disorders,however,further investigation is needed to support the research findings and implement it in clinical practice.展开更多
Background:Hormonal treatment and response as a predictor of sperm retrieval prior to microdissection testicular sperm extraction(micro-TESE)are not well established in the current literature.This study aimed to inves...Background:Hormonal treatment and response as a predictor of sperm retrieval prior to microdissection testicular sperm extraction(micro-TESE)are not well established in the current literature.This study aimed to investigate the hormonal response as a predictor of sperm retrieval among men with nonobstructive azoospermia(NOA).Methods:Seventy-seven consecutive patients who had testosterone levels≤14 nmol/L were treated medically with an aromatase inhibitor or recombinant human chorionic gonadotropin(rec-hCG)prior to micro-TESE and were included.Thirty-four(44.2%)had unexplained NOA(UNEX),25(32.5%)had Klinefelter syndrome(KS),8(10.4%)had a history of cryptorchidism(UDT),4(5.2%)had microdeletion of the Azoospermia factor C(AZFc),and 6(7.8%)were treated previously with chemotherapy.Baseline and post-treatment serum hormonal levels were documented.Pre-op testosterone levels were entered into binary logistic regressions with age,Follicle-stimulating hormone(FSH),and Luteinizing hormone(LH)levels to test for significance with sperm retrieval.We then built logistic regression models to identify predictors of successful surgical sperm retrieval(SSR).Results:Forty-five patients(58%)had successful retrieval.In 32 patients(42%),no sperm was retrieved.Both the mean pre-op testosterone and the mean testosterone change between the two groups were significant(p=0.02 and p=0.011,respectively).Receiver operating characteristic(ROC)analysis demonstrated an area under the curve(AUC)of 0.785(95%CI=0.685-0.886,p<0.001).The Youden index coefficient was calculated for KS and UNEX.The cut-off point for KS was established at 0.764(sensitivity=0.875,false positive rate[FPR]=0.111),and 0.215 for UNEX(sensitivity=0.438,FPR=0.222).We also observed a correlation between age and SSR(p=0.05).In KS patients,SSR was determined by pre-op testosterone levels irrespective of age.Conclusion:Pre-operative hormonal response is a predictor for SSR in NOA patients who were treated medically.This data may help during pre-operative counselling.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
Testosterone affects several organs in the body and is very important for male well-being.Aging men with late-onset hypogonadism(LOH)experience physiologic,psychiatric,and sexual symptoms related to a decline in the s...Testosterone affects several organs in the body and is very important for male well-being.Aging men with late-onset hypogonadism(LOH)experience physiologic,psychiatric,and sexual symptoms related to a decline in the serum concentration of testosterone with age.However,it is well-known that the extent of the decline in testosterone concentration does not correlate with the severity of LOH-related symptoms.Therefore,it is difficult to diagnose and treat patients with LOH.In addition,the symptoms,response to testosterone replacement therapy(TRT),and medical insurance coverage differ among ethnicities and countries.The evaluation of testosterone is essential for the diagnosis and treatment of LOH.The effects of testosterone are determined not only by the serum testosterone concentration but also by the androgen receptor sensitivity.A low number of glutamine repeats is indicative of high androgenic activity,and the number shows ethnicity-related differences(fewer in African American than in Caucasian people and more in East Asian people).The diagnosis of LOH is typically made using subjective symptoms and the serum testosterone concentration.The Aging Male Symptoms scale is widely used to evaluate the symptoms.The normal range of total testosterone concentration varies around the world;therefore,clinicians should follow the guidelines of their regional academic society.The principal treatment for LOH is TRT.There are many types of TRT and other treatment strategies are also available.Thus,physicians should treat LOH according to each patient’s situation,considering related disorders,such as diabetes,osteoporosis,metabolic syndrome,and depression.展开更多
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
Azoospermia,defined as the absence of sperm in the ejaculate,is a well-documented consequence of exogenous testosterone(ET)and anabolic–androgenic steroid(AAS)use.These agents suppress the hypothalamic–pituitary–go...Azoospermia,defined as the absence of sperm in the ejaculate,is a well-documented consequence of exogenous testosterone(ET)and anabolic–androgenic steroid(AAS)use.These agents suppress the hypothalamic–pituitary–gonadal(HPG)axis,leading to reduced intratesticular testosterone levels and impaired spermatogenesis.This review examines the pathophysiological mechanisms underlying azoospermia and outlines therapeutic strategies for recovery.Azoospermia is categorized into pretesticular,testicular,and post-testicular types,with a focus on personalized treatment approaches based on the degree of HPG axis suppression and baseline testicular function.Key strategies include discontinuing ET and monitoring for spontaneous recovery,particularly in patients with shorter durations of ET use.For cases of persistent azoospermia,gonadotropins(human chorionic gonadotropin[hCG]and follicle-stimulating hormone[FSH])and selective estrogen receptor modulators(SERMs),such as clomiphene citrate,are recommended,either alone or in combination.The global increase in exogenous testosterone use,including testosterone replacement therapy and AAS,underscores the need for improved management of associated azoospermia,which can be temporary or permanent depending on individual factors and the type of testosterone used.Additionally,the manuscript discusses preventive strategies,such as transitioning to short-acting testosterone formulations or incorporating low-dose hCG to preserve fertility during ET therapy.While guidelines for managing testosterone-related azoospermia remain limited,emerging research indicates the potential efficacy of hormonal stimulation therapies.However,there is a notable lack of well-structured,controlled,and long-term studies addressing the management of azoospermia related to exogenous testosterone use,highlighting the need for such studies to inform evidence-based recommendations.展开更多
One major challenge in male factor infertility is nonobstructive azoospermia(NOA),which is characterized by spermatozoa-deficient semen without physical duct blockage.This review offers a thorough overview of the hist...One major challenge in male factor infertility is nonobstructive azoospermia(NOA),which is characterized by spermatozoa-deficient semen without physical duct blockage.This review offers a thorough overview of the histopathology of the testes in NOA cases,clarifying its complex etiology and emphasizing the possible value of histopathology inspection for both diagnosis and treatment.Variable histopathological findings have been linked to NOA,such as tubular hyalinization,Sertoli cell-only syndrome,hypospermatogenesis,and germ cell arrest.Understanding the pathophysiology and forecasting the effectiveness of treatment are further enhanced by both morphometric and ultrastructural analyses.The potential significance of testicular biopsy in forecasting reproductive outcomes is assessed,especially concerning assisted reproductive technologies like intracytoplasmic sperm injection(ICSI).Besides,testicular microlithiasis,serum hormone profiles,and testicular size are investigated concerning NOA histopathology.It is concluded that understanding the histopathological patterns in NOA is crucial for its accurate diagnosis and appropriate management.Further research is still warranted to improve understanding of the complex pathophysiology underlying NOA.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
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
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
Primary ciliary dyskinesia(PCD)is a clinically rare,genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections,male infertility,tympanitis,and laterality abnormalities...Primary ciliary dyskinesia(PCD)is a clinically rare,genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections,male infertility,tympanitis,and laterality abnormalities.PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia.Here,we identified a novel nonsense mutation,c.466G>T,in cilia-and flagella-associated protein 300(CFAP300)resulting in a stop codon(p.Glu156*)through whole-exome sequencing(WES).The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm(IDA)and outer dynein arm(ODA).Bioinformatic programs predicted that the mutation is deleterious.Successful pregnancy was achieved through intracytoplasmic sperm injection(ICSI).Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.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
文摘Simulation can be defined as malingering, or sometimes functional visual loss (FVL). It manifests as either simulating an ophthalmic disease (positive simulation), or denial of ophthalmic disease (negative simulation). Conscious behavior and compensation or indemnity claims are prominent features of simulation. Since some authors suggest that this is a manifestation of underlying psychopathology, even conversion is included in this context. In today's world, every ophthalmologist can face with simulation of ophthalmic disease or disorder. In case of simulation suspect, the physician's responsibility is to prove the simulation considering the disease/disorder first, and simulation as an exclusion. In simulation examinations, the physician should be firm and smart to select appropriate test(s) to convince not only the subject, but also the judge in case of indemnity or compensation trials. Almost all ophthalmic sensory and motor functions including visual acuity, visual field, color vision and night vision can be the subject of simulation. Examiner must be skillful in selecting the most appropriate test. Apart from those in the literature, we included all kinds of simulation in ophthalmology. In addition, simulation examination techniques, such as, use of OCT (optical coherence tomography), frequency doubling perimetry (FDP), and modified polarization tests were also included. In this review, we made a thorough literature search, and added our experiences to give the readers up-to-date information on malingering or simulation in ophthalmology.
文摘· Simulation can be defined as malingering, or sometimes functional visual loss (FVL). It manifests as either simulating an ophthalmic disease (positive simulation), or denial of ophthalmic disease (negative simulation). Conscious behavior and compensation or indemnity claims are prominent features of simulation. Since some authors suggest that this is a manifestation of underlying psychopathology, even conversion is included in this context. In today’s world, every ophthalmologist can face with simulation of ophthalmic disease or disorder. In case of simulation suspect, the physician’s responsibility is to prove the simulation considering the disease/disorder first, and simulation as an exclusion. In simulation examinations, the physician should be firm and smart to select appropriate test (s) to convince not only the subject, but also the judge in case of indemnity or compensation trials. Almost all ophthalmic sensory and motor functions including visual acuity, visual field, color vision and night vision can be the subject of simulation. Examiner must be skillful in selecting the most appropriate test. Apart from those in the literature, we included all kinds of simulation in ophthalmology. In addition, simulation examination techniques, such as, use of optical coherence tomography, frequency doubling perimetry (FDP), and modified polarization tests were also included. In this review, we made a thorough literature search, and added our experiences to give the readers up -to -date information on malingering or simulation in ophthalmology. ·
文摘The P300, an endogenous subcomponent of the event-related potential, is thought to reflect cognitive processes. The event-related potential evoked by the old-new memory recognition task in the oddball paradigm is suitable for examining the neural processes involved in malingered neurocognitive deficits. Forty-four undergraduates were randomly assigned to a simulated malingering group and a truth-telling group, Another 22 patients with head injudes were enrolled as a control group. All participants completed the old-new memory recognition task in the oddball paradigm. The mean P300 amplitude of the simulated malingering group was significantly reduced compared with the truth-telling group （P 〈 0.01）, but was increased compared with the control group （P〈 0.01）. These results revealed that the P300, evoked by the old-new memory recognition task of the oddball paradigm, may be a helpful indicator for determining cognitive malingering.
文摘The main high points ofthis tour are sightseeing inthe Maling River Valley, riftvalley drifting, a visit to theBouyei village, and theGuizhou Wedding CustomsMuseum.
基金supported by the Science and Technology Major Program of Bingtuan,China (2023AA008)the National Natural Science Foundation of China (31960369)+1 种基金the Bingtuan Science and Technology Program,China (2025DA001)the Henan Provincial Science and Technology Research Project,China (222102110200)。
文摘Recent studies have shown that lipid metabolism is a key factor affecting anther development and male fertility.However,how plants regulating the metabolic balance of multiple lipids to ensure proper anther development and male fertility remains unclear.Analyzing lipid molecules related to anther fertility and genes responsible for their biosynthesis is crucial for understanding the physiological significance of lipid metabolism in crop fertility.In this study,we compared the transcriptome and the composition and content of lipids in anthers of two upland cotton(Gossypium hirsutum) materials,Shida 98(WT) and its nearly-isogenic male sterile line Shida 98A(MS).Transcriptomics analysis identified many differentially expressed genes(DEGs) between the two materials,with the genes of the alpha-linolenic acid metabolism pathway being the most significantly associated with the male sterility phenotype.Investigations on lipids revealed that the MS anthers over-accumulated free fatty acids(FFAs),phosphatidic acid(PA),mono-and di-galactosyldiacylglycerol(MGDG and DGDG),and had a decreased content of triacylglycerol(TAG),which was closely related to the abnormal metabolism of alpha-linolenic acid(C18:3);therefore,the major lipids containing C18:3-acyl chains,such as PA,MGDG,DGDG,and TAG,are proposed to play a major role in cotton anther development.We also showed that an excessive level of MGDG and DGDG caused jasmonic acid(JA) overaccumulation in MS anthers,which in turn inhibited the expression of GhFAD3 and consequently reduced the C18:3 content,presumably via a feedback regulation mechanism,ultimately affecting plant fertility.Together,our results revealed the importance of a balanced lipid metabolism in regulating the development of cotton anther and pollen and consequently male fertility.
文摘Mammalian fertilization involves the migration of spermatozoa through the female reproductive system.Early embryonic development is a consequence of several steps and signaling pathways being activated,as well as biochemical and morphological modifications of spermatozoa that enable them to penetrate the membrane of mature oocytes.There are some crucial steps known to clearly explain the process of fertilization,starting with hyperactivation of spermatozoa,mutual recognition,and binding of gametes mediated by receptors located on the surface membranes of both gametes.The final step is followed by oocyte activation,which is primarily triggered via sperm-derived factors,inducing a sharp increase in intracellular calcium levels,eventually leading to polyspermy block.This review integrates current knowledge of the molecular and physiological events governing fertilization,emphasizing how ion regulation and signaling pathways converge to enable sperm function and oocyte activation.Special attention is given to sperm-derived factors such as phospholipase C zeta(PLCζ)and post-acrosomal sheath WW domain-binding protein(PAWP),which play essential roles in triggering calcium release and supporting early embryonic development.
基金financially assisted to Timanshi Chansoriya of the fellowship grant of UGC-NFPwD,New Delhi sanctioned vide UGC F.No.01-01/2019-Sch dated 06.11.2020(Serial No.352 ID:NFPWD-2018-20-UTP-6522).
文摘Objective:To investigate the sterilizing potential of zinc gluconate,calcium chloride(CaCl_(2))and cadmium chloride(CdCl_(2))following a single intratesticular administration in adult male rats.Methods:60 adult male Wistar albino rats(Rattus norvegicus)weighing 160-200 g and aged 5-6 months randomly received a single intratesticular injection of normal saline(Group A),zinc gluconate 13.3 mg/mL plus L-Arginine(Group B),20%CaCl_(2)(Group C),and CdCl_(2)0.5 mg/kg body weight plus ethylenediaminetetraacetic acid(EDTA)(Group D),respectively,along the entire route from the caudoventral aspect of each testis.They were euthanized up to 180 days to evaluate reproductive tract toxicology.Results:The reproductive organ weights were markedly reduced,with testes severely atrophied in group B,pea-sized and stony hard in group C,and moderately reduced in group D.Azoospermia was evident in groups B and C,while sperm concentration was reduced to<1 million/mL with zero sperm motility in group D.Rats of groups B and C failed to show mounting and copulatory behaviour.A completely disorganized mesh of cellular elements was observed in the seminiferous tubules of group B,while pyknotic germ cell and arrest of spermatogenesis,exfoliated germ cells,occasional syncytial bodies and smaller Leydig cells were evident in groups C and D.Significantly reduced testosterone levels,increased luteinizing hormone(LH)and follicle-stimulating hormone(FSH)levels,returned to normal after 90 days in group D.Conclusions:Zinc gluconate and CaCl_(2)injections severely affected the reproductive organs and libido and rats treated with CdCl_(2)exhibited diminished spermatogenesis with normal libido.Thus,the need-based selection of intratesticular agents should consider their distinct effects on spermatogenesis,libido,and hormonal balance for achieving targeted sterilization outcomes.
文摘Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor receptor 2(HER2)-negative and estrogen receptor(ER)-positive,and lacks routine screening,leading to delayed diagnosis and advanced disease.Major risk factors include hormonal imbalance,radiation exposure,obesity,alcohol use,and Breast Cancer Gene 1 and 2(BRCA1/2)mutations.Clinically,it may resemble gynecomastia but usually appears as a unilateral,painless mass or nipple discharge.Advances in imaging and liquid biopsy have enhanced early detection.Molecular mechanisms involve hormonal signaling,HER2/epidermal growth factor receptor(EGFR)pathways,tumor suppressor gene alterations,and epigenetic changes.While standard treatments mirror those for female breast cancer,emerging options such as cyclin-dependent kinase 4 and 6(CDK4/6),and poly(ADP-ribose)polymerase(PARP)inhibitors,immunotherapy,and precision medicine are reshaping management.Incorporating artificial intelligence,molecular profiling,and male-specific clinical trials is essential to improve outcomes and bridge current diagnostic and therapeutic gaps.
文摘Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to its therapeutic properties,but its exact role and molecular mechanisms in treatment of reproductive dysfunction remain unclear.Methods:During this study,36 rats were randomly divided into six groups(n=6):control,CYP-induced(60 mg/kg),standard(leuprolide 3 mg/kg)and three treatment groups receiving aqueous,ethanolic,and oil extracts(50 mg/kg or 20 mL/kg)for post-toxicity induction.Results:The finding represented that exposure of CYP significantly increased oxidative stress,disrupted testicular architecture,and markedly reduced testosterone levels(P<0.05).Importantly,Crocus sativus L.treatment alleviated these changes by increasing the expression of Nrf2(nuclear factor erythroid 2-related factor 2),restoring the activity of antioxidant enzymes,and enhancing testicular histomorphology.Surprisingly,molecular docking established a high binding affinity of Crocus sativus L.phytoconstituents such as gallic acid,cinnamic acid and quercetin to the Nrf2-Keap1 complex.It is worth noting that,Crocus sativus L.exhibited a high level of protection against reproductive toxicity caused by CYP in male rats,which was mediated by the activation of Nrf2 pathway,reduction of oxidative damage,and favorable ADMET characteristics.Conclusion:Notably,this research provides a more valid,safe,and effective method of developing new drugs for reproductive disorders,however,further investigation is needed to support the research findings and implement it in clinical practice.
文摘Background:Hormonal treatment and response as a predictor of sperm retrieval prior to microdissection testicular sperm extraction(micro-TESE)are not well established in the current literature.This study aimed to investigate the hormonal response as a predictor of sperm retrieval among men with nonobstructive azoospermia(NOA).Methods:Seventy-seven consecutive patients who had testosterone levels≤14 nmol/L were treated medically with an aromatase inhibitor or recombinant human chorionic gonadotropin(rec-hCG)prior to micro-TESE and were included.Thirty-four(44.2%)had unexplained NOA(UNEX),25(32.5%)had Klinefelter syndrome(KS),8(10.4%)had a history of cryptorchidism(UDT),4(5.2%)had microdeletion of the Azoospermia factor C(AZFc),and 6(7.8%)were treated previously with chemotherapy.Baseline and post-treatment serum hormonal levels were documented.Pre-op testosterone levels were entered into binary logistic regressions with age,Follicle-stimulating hormone(FSH),and Luteinizing hormone(LH)levels to test for significance with sperm retrieval.We then built logistic regression models to identify predictors of successful surgical sperm retrieval(SSR).Results:Forty-five patients(58%)had successful retrieval.In 32 patients(42%),no sperm was retrieved.Both the mean pre-op testosterone and the mean testosterone change between the two groups were significant(p=0.02 and p=0.011,respectively).Receiver operating characteristic(ROC)analysis demonstrated an area under the curve(AUC)of 0.785(95%CI=0.685-0.886,p<0.001).The Youden index coefficient was calculated for KS and UNEX.The cut-off point for KS was established at 0.764(sensitivity=0.875,false positive rate[FPR]=0.111),and 0.215 for UNEX(sensitivity=0.438,FPR=0.222).We also observed a correlation between age and SSR(p=0.05).In KS patients,SSR was determined by pre-op testosterone levels irrespective of age.Conclusion:Pre-operative hormonal response is a predictor for SSR in NOA patients who were treated medically.This data may help during pre-operative counselling.
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.
文摘Testosterone affects several organs in the body and is very important for male well-being.Aging men with late-onset hypogonadism(LOH)experience physiologic,psychiatric,and sexual symptoms related to a decline in the serum concentration of testosterone with age.However,it is well-known that the extent of the decline in testosterone concentration does not correlate with the severity of LOH-related symptoms.Therefore,it is difficult to diagnose and treat patients with LOH.In addition,the symptoms,response to testosterone replacement therapy(TRT),and medical insurance coverage differ among ethnicities and countries.The evaluation of testosterone is essential for the diagnosis and treatment of LOH.The effects of testosterone are determined not only by the serum testosterone concentration but also by the androgen receptor sensitivity.A low number of glutamine repeats is indicative of high androgenic activity,and the number shows ethnicity-related differences(fewer in African American than in Caucasian people and more in East Asian people).The diagnosis of LOH is typically made using subjective symptoms and the serum testosterone concentration.The Aging Male Symptoms scale is widely used to evaluate the symptoms.The normal range of total testosterone concentration varies around the world;therefore,clinicians should follow the guidelines of their regional academic society.The principal treatment for LOH is TRT.There are many types of TRT and other treatment strategies are also available.Thus,physicians should treat LOH according to each patient’s situation,considering related disorders,such as diabetes,osteoporosis,metabolic syndrome,and depression.
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.
文摘Azoospermia,defined as the absence of sperm in the ejaculate,is a well-documented consequence of exogenous testosterone(ET)and anabolic–androgenic steroid(AAS)use.These agents suppress the hypothalamic–pituitary–gonadal(HPG)axis,leading to reduced intratesticular testosterone levels and impaired spermatogenesis.This review examines the pathophysiological mechanisms underlying azoospermia and outlines therapeutic strategies for recovery.Azoospermia is categorized into pretesticular,testicular,and post-testicular types,with a focus on personalized treatment approaches based on the degree of HPG axis suppression and baseline testicular function.Key strategies include discontinuing ET and monitoring for spontaneous recovery,particularly in patients with shorter durations of ET use.For cases of persistent azoospermia,gonadotropins(human chorionic gonadotropin[hCG]and follicle-stimulating hormone[FSH])and selective estrogen receptor modulators(SERMs),such as clomiphene citrate,are recommended,either alone or in combination.The global increase in exogenous testosterone use,including testosterone replacement therapy and AAS,underscores the need for improved management of associated azoospermia,which can be temporary or permanent depending on individual factors and the type of testosterone used.Additionally,the manuscript discusses preventive strategies,such as transitioning to short-acting testosterone formulations or incorporating low-dose hCG to preserve fertility during ET therapy.While guidelines for managing testosterone-related azoospermia remain limited,emerging research indicates the potential efficacy of hormonal stimulation therapies.However,there is a notable lack of well-structured,controlled,and long-term studies addressing the management of azoospermia related to exogenous testosterone use,highlighting the need for such studies to inform evidence-based recommendations.
文摘One major challenge in male factor infertility is nonobstructive azoospermia(NOA),which is characterized by spermatozoa-deficient semen without physical duct blockage.This review offers a thorough overview of the histopathology of the testes in NOA cases,clarifying its complex etiology and emphasizing the possible value of histopathology inspection for both diagnosis and treatment.Variable histopathological findings have been linked to NOA,such as tubular hyalinization,Sertoli cell-only syndrome,hypospermatogenesis,and germ cell arrest.Understanding the pathophysiology and forecasting the effectiveness of treatment are further enhanced by both morphometric and ultrastructural analyses.The potential significance of testicular biopsy in forecasting reproductive outcomes is assessed,especially concerning assisted reproductive technologies like intracytoplasmic sperm injection(ICSI).Besides,testicular microlithiasis,serum hormone profiles,and testicular size are investigated concerning NOA histopathology.It is concluded that understanding the histopathological patterns in NOA is crucial for its accurate diagnosis and appropriate management.Further research is still warranted to improve understanding of the complex pathophysiology underlying NOA.
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.
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(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supported by the China Postdoctoral Science Foundation Grant(2023M734294)Jiangsu Provincial Medical Key Discipline Cultivation Unit(JSDW202215)the National Natural Science Foundation of China(No.82001618).
文摘Primary ciliary dyskinesia(PCD)is a clinically rare,genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections,male infertility,tympanitis,and laterality abnormalities.PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia.Here,we identified a novel nonsense mutation,c.466G>T,in cilia-and flagella-associated protein 300(CFAP300)resulting in a stop codon(p.Glu156*)through whole-exome sequencing(WES).The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm(IDA)and outer dynein arm(ODA).Bioinformatic programs predicted that the mutation is deleterious.Successful pregnancy was achieved through intracytoplasmic sperm injection(ICSI).Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
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.
