The cause of asthenozoospermia(AZS)is not well understood because of its complexity and heterogeneity.Although some gene mutations have been identified as contributing factors,they are only responsible for a small num...The cause of asthenozoospermia(AZS)is not well understood because of its complexity and heterogeneity.Although some gene mutations have been identified as contributing factors,they are only responsible for a small number of cases.Radial spokes(RSs)are critical for adenosine triphosphate-driven flagellar beating and axoneme stability,which is essential for flagellum motility.In this study,we found novel compound heterozygous mutations in leucine-rich repeat-containing protein 23(LRRC23;c.1018C>T:p.Q340X and c.881_897 Del:p.R295Gfs*32)in a proband from a nonconsanguineous family with AZS and male infertility.Diff-Quik staining and scanning electron microscopy revealed no abnormal sperm morphology.Western blotting and immunofluorescence staining showed that these mutations suppressed LRRC23 expression in sperm flagella.Additionally,transmission electron microscopy showed the absence of RS3 in sperm flagella,which disrupts stability of the radial spoke complex and impairs motility.Following in vitro fertilization and embryo transfer,the proband’s spouse achieved successful pregnancy and delivered a healthy baby.In conclusion,our study indicates that two novel mutations in LRRC23 are associated with AZS,but successful fertility outcomes can be achieved by in vitro fertilization-embryo transfer techniques.展开更多
Asthenozoospermia （AS） is a common cause of human male infertility. In one study, more than 80% of the samples from infertile men had reduced sperm motility. Seminal plasma is a mixture of secretions from the testis...Asthenozoospermia （AS） is a common cause of human male infertility. In one study, more than 80% of the samples from infertile men had reduced sperm motility. Seminal plasma is a mixture of secretions from the testis, epididymis and several male accessory glands, including the prostate, seminal vesicles and Cowper＇s gland. Studies have shown that seminal plasma contains proteins that are important for sperm motility. To further explore the pathophysiological character of AS, we separated the seminal plasma proteins from AS patients and healthy donors using sodium dodecyl sulfate polyacrylamide gel electrophoresis and in-gel digestion, and then subjected the proteins to liquid chromatography-mass spectrometry （LC-MS/MS） analysis. A total of 741 proteins were identified in the seminal plasma, with a false discovery rate of 3.3%. Using spectral counting, we found that 45 proteins were threefold upregulated and 56 proteins were threefold downregulated in the AS group when compared with the control. Most of these proteins originated from the epididymis and prostate. This study identified a rich source of biomarker candidates for male infertility and indicates that functional abnormalities of the epididymis and prostate can contribute to AS. We identified D J-1--a protein that has been shown elsewhere to be involved in the control of oxidative stress （OS）-as a downregulated protein in AS seminal plasma. The levels of D J-1 in AS seminal plasma were about half of those in the control samples. In addition, the levels of reactive oxygen species were 3.3-fold higher in the AS samples than in the controls. Taken together, these data suggest that downregulation of DJ-1 is involved in OS in semen, and therefore affects the quality of the semen.展开更多
Human spermatozoa encounter an osmotic decrease from 330 to 290 mOsm I-z when passing through the female reproductive tract. We aimed to evaluate the role of chloride channels in volume regulation and sperm motility f...Human spermatozoa encounter an osmotic decrease from 330 to 290 mOsm I-z when passing through the female reproductive tract. We aimed to evaluate the role of chloride channels in volume regulation and sperm motility from patients with asthenozoospermia. Spermatozoa were purified using Percoll density gradients. Sperm volume was measured as the forward scatter signal using flow cytometry. Sperm motility was analyzed using computer-aided sperm analysis （CASA）. When transferred from an isotonic solution （330 mOsm I-z） to a hypotonic solution （290 mOsm I-Z）, cell volume was not changed in spermatozoa from normozoospermic men; but increased in those from asthenozoospermic samples. The addition of the chloride channel blockers, 4,4＇-diisothiocyanatostilbene-2,2＇- isulfonic acid （DIDS） or 5-nitro-2-（3-phenylpropylamino） benzoic acid （NPPB） to the hypotonic solution caused the normal spermatozoa to swell but did not increase the volume of those from the asthenozoospermic semen. DIDS and NPPB decreased sperm motility in both sets of semen samples. The inhibitory effect of NPPB on normal sperm motility was much stronger than on spermatozoa from the asthenozoospermic samples. Both sperm types expressed CIC-3 chloride channels, but the expression levels in the asthenozoospermic samples were much lower, especially in the neck and mid-piece areas. Spermatozoa from men with asthenozoospermia demonstrated lower volume regulating capacity, mobility, and CIC-3 expression levels （especially in the neck） than did normal spermatozoa. Thus, chloride channels play important roles in the regulation of sperm volume and motility and are downregulated in cases of asthenozoospermia.展开更多
A growing number of researches have shown that ouabain can regulate mammalian sperm function and male reproduction by modulating the sperm motility, capacitation and acrosome reaction in vitro. This study further exam...A growing number of researches have shown that ouabain can regulate mammalian sperm function and male reproduction by modulating the sperm motility, capacitation and acrosome reaction in vitro. This study further examined the relationship between ouabain and asthenozoospermia. In this study, the rat was intraperitoneally injected with ouabain at different concentrations（low-dose ouabain group： 12.5 μg/kg body weight per day, and high-dose ouabain group： 25 μg/kg body weight per day） for 30 days to establish the asthenozoospermia model. The sperms from 60 males with normal fertility were incubated with ouabain of gradient concentrations（10-7–10-2mol/L） for 4 h. The sperm motility was evaluated under a microscope. Moreover, the endogenous ouabain（EO） level was determined in seminal plasma of mild or severe asthenozoospermia patients and males with normal fertility by competitive inhibition ELISA. The results showed that the sperm motility was significantly diminished in the rats treated with different concentrations of ouabain. The number of motile sperms（grades a and b） was decreased greatly in a time- and dose-dependent manner in 10-5–10-2mol/L ouabain groups（P0.01）, while no obvious change in sperm motility was observed in 10-7–10-6mol/L groups even for 4-h incubation（P0.05）. Furthermore, the EO level was significantly increased in asthenozoospermia patients as compared with that in males with normal fertility（25.27±1.71 μg/L in mild asthenozoospermia patients, 26.52±1.82 μg/L in severe asthenozoospermia patients, 19.31±1.45 μg/L in normal fertility men）（P0.01）. In conclusion, rat asthenozoospermia was successfully established by intraperitoneal injection of ouabain, and 10-5mol/L ouabain was sufficient enough to inhibit sperm motility in vitro. Moreover, EO, a normal constituent of seminal plasma, was highly expressed in asthenozoospermia males as compared with normal fertility ones.展开更多
Spermatozoa are not mature until they transit the epididymis where they acquire motility and the ability to fertilize an egg through sequential modifications. The epididymis has three functional regions, caput, corpus...Spermatozoa are not mature until they transit the epididymis where they acquire motility and the ability to fertilize an egg through sequential modifications. The epididymis has three functional regions, caput, corpus, and cauda, and the luminal proteins of the epididymis play important roles in the above modifications. However, the proteins with differential enrichment between the caput and cauda are still largely unknown. To reveal the functions of the caput and cauda during sperm maturation, luminal proteins from caput and cauda of mice were analyzed by isobaric tag for relative and absolute quantitation （iTRAQ）. Overall, 128 differentially enriched proteins were found, of which 46 were caput enriched and 82 were cauda enriched. Bioinformatic analysis showed that lipid metabolism was active in the caput; while anion- and cation-binding activity and phosphorus and organophosphate metabolism were active in the cauda. A new epididymal luminal protein, the caput-enriched PDZ domain containing 1 （Pdzkl）, also named Na^＋/H^＋ exchange regulatory cofactor 3 （NHERF3）, which plays a critical role in cholesterol metabolism and carnitine transport, was found in the lipid metabolism. Western blotting and immunofluorescence analyses showed that Pdzkl was expressed in the epididymis but not in the testis, and localized at the middle piece of the sperm tail. Pdzkl protein level was also reduced in the spermatozoa in case of asthenozoospermic patients compared with that in normozoospermic men, suggesting that Pdzkl may participate in sperm maturation regulation and may be associated with male infertility. These results may provide new insights into the mechanisms of sperm maturation and male infertility.展开更多
Idiopathic asthenozoospermia,a common factor in male infertility,is characterized by altered sperm motility function in fresh ejaculate.Although theβ-defensin 126(DEFB126)protein is associated with asthenozoospermia,...Idiopathic asthenozoospermia,a common factor in male infertility,is characterized by altered sperm motility function in fresh ejaculate.Although theβ-defensin 126(DEFB126)protein is associated with asthenozoospermia,DEFB126 gene polymorphisms have not been extensively studied.Therefore,the association between DEFB126 gene polymorphisms and asthenozoospermia requires further investigation.Screening was performed by semen analysis,karyotype analysis,and Y microdeletion detection,and 102 fertile men and 106 men with asthenozoospermia in Chengdu,China,were selected for DEFB126 gene sequence analyses.Seven nucleotide mutations and two nucleotide deletions in the DEFB126 gene were detected.rs11467417(317-318 del/del),rs11467497(163-166 wt/del),c.152T>C,and c.227A>G were significantly different between the control and asthenozoospermia groups,likely representing high-risk genetic factors for asthenozoospermia among males.DEFB126 expression was not observed in sperm with rs11467497 homozygous deletion and was unstable in sperm with rs11467417 homozygous deletion.The rs11467497 four-nucleotide deletion leads to truncation of DEFB126 at the carboxy-terminus,and the rs11467417 binucleotide deletion produces a non-stop messenger RNA(mRNA).The above deletions may be responsible for male hypofertility and infertility by reducing DEFB126 affinity to sperm surfaces.Based on in silico analysis,the amino acids 51M and 76K are located in the highly conserved domain;c.152T>C(M51T)and c.227A>G(K76R)are predicted to be damaging and capable of changing alternative splice,structural and posttranslational modification sites of the RNA,as well as the secondary structure,structural stability,and hydrophobicity of the protein,suggesting that these mutations are associated with asthenozoospermia.展开更多
Asthenozoospermia is a common cause of male infertility and is characterized by reduced forward motility of spermatozoa. The pathogenesis of asthenozoospermia remains unclear. DJ-1 is a ubiquitous protein, widely expr...Asthenozoospermia is a common cause of male infertility and is characterized by reduced forward motility of spermatozoa. The pathogenesis of asthenozoospermia remains unclear. DJ-1 is a ubiquitous protein, widely expressed in the liver, skeletal muscle, kidney, brain and testis. It has been found correlated with many diseases including male infertility. This review presents the novel concept that the endogenous antioxidant properties of DJ-I in sperm is associated with asthenozoospermia. Thus, DJ-l is likely a new target for the treatment of asthenozoospermia.展开更多
Male infertility contributes to 20%–70%of infertile couple cases worldwide.One of the key challenges in this area is asthenozoospermia or reduced sperm motility.A particular subset,known as isolated asthenozoospermia...Male infertility contributes to 20%–70%of infertile couple cases worldwide.One of the key challenges in this area is asthenozoospermia or reduced sperm motility.A particular subset,known as isolated asthenozoospermia(iASZ),in which low motility occurs without abnormalities in sperm count or shape,often goes unnoticed and is not well understood.This narrative review attempts to compile the state of knowledge regarding the etiology,diagnosis,and treatment of iA SZ and to identify knowledge gaps that need further investigation with an emphasis on physiological,genetic,and molecular mechanisms.We conducted a focused literature search using PubMed and Web of Science,covering studies published between 2000 and 2024.We included articles that explored the structure,function,diagnosis,and treatment of iASZ.We find sperm motility is influenced by multiple factors,from structural components like mitochondria and the flagellum,to biochemical signals and genetic mutations.In men with iASZ,issues such as mitochondrial dysfunction,oxidative stress,or specific gene defects may impair motility.While routine semen analysis helps flag low motility,it often fails to explain why it occurs—highlighting the need for advanced tests like DNA fragmentation tests,genetic screening,and high-resolution imaging.As regards treatment,lifestyle changes,varicocele surgery,and antioxidants can offer some benefit.Assisted reproduction techniques,especially intracytoplasmic sperm injection(ICSI),remain central for achieving pregnancy when other options fail.iA SZ deserves more attention as a distinct and treatable cause of male infertility.By improving how we diagnose and manage this condition,supported by further research,we can offer better outcomes for affected couples hoping to conceive.展开更多
Eissa et al.'s review warmly invites readers into the often-overlooked realm of isolated asthenozoospermia(iASZ),a condition marked by reduced sperm motility that affects 16%–24%of male infertility cases.With a n...Eissa et al.'s review warmly invites readers into the often-overlooked realm of isolated asthenozoospermia(iASZ),a condition marked by reduced sperm motility that affects 16%–24%of male infertility cases.With a nod to the authors’dedication,this work masterfully compiles insights into the physiological,genetic,and molecular underpinnings of iASZ,offering a clear guide to its etiology,diagnosis,and management.展开更多
Objective:This study investigated the outcomes of microsurgical subinguinal varicocelectomy(MSV)on semen and hormonal parameters in cases with isolated sperm defects(oligozoospermia,asthenozoospermia,or teratozoosperm...Objective:This study investigated the outcomes of microsurgical subinguinal varicocelectomy(MSV)on semen and hormonal parameters in cases with isolated sperm defects(oligozoospermia,asthenozoospermia,or teratozoospermia).Methods:A retrospective review of charts of patients who underwent MSV for clinically palpable varicocele between January 1,2011 and January 1,2019 at Hamad Medical Corporation was undertaken.All patients diagnosed with isolated oligozoospermia,asthenozoospermia,or teratozoospermia in the preoperative semen analysis were included.Men with multiple sperm defects,genetic abnormalities,azoospermia,history of genitourinary infection,exposure to chemotherapy or radiotherapy,or prior use of peri-operative fertility treatment were excluded.Data extracted from the electronic medical records included(collected before MSV and up to 6 months postoperatively):demographics(age),clinical data(fertility-related medical history and surgical interventions),family history(consanguinity and infertility),physical examination findings from general and local genital exam(varicocele side and grade),laboratory data such as semen analysis,sperm DNA fragmentation tests,and hormone levels(follicle-stimulating hormone,luteinizing hormone,total testosterone,estradiol,and prolactin),and imaging(scrotal color Doppler ultrasound).Results:A total of 331 patients with isolated sperm defects were included.Postoperatively,83.3%of patients showed an improvement in sperm concentration with a median increase of 7 millions/mL.Postoperatively,76.7%of isolated asthenozoospermic patients showed an improvement in total motility and 66.0%had an improvement in progressive motility with median increases of 15.0%and 7.5%,respectively.Postoperatively,70.0%of the teratozoospermic patients showed an improvement in normal sperm morphology with a median increase of 6%.No changes were observed in other semen or hormone parameters that were examined.Conclusion:MSV is a valid and effective treatment modality for patients with isolated sperm defects that significantly corrects their respective semen abnormality and improves their chances of natural conception.展开更多
Multiple morphological abnormalities of the flagella(MMAF)represent a severe form of sperm defects leading to asthenozoospermia and male infertility.In this study,we identified a novel homozygous splicing mutation(c.8...Multiple morphological abnormalities of the flagella(MMAF)represent a severe form of sperm defects leading to asthenozoospermia and male infertility.In this study,we identified a novel homozygous splicing mutation(c.871-4 ACA>A)in the adenylate kinase 7(AK7)gene by whole-exome sequencing in infertile individuals.Spermatozoa from affected individuals exhibited typical MMAF characteristics,including coiled,bent,short,absent,and irregular flagella.Transmission electron microscopy analysis showed disorganized axonemal structure and abnormal mitochondrial sheets in sperm flagella.Immunofluorescence staining confirmed the absence of AK7 protein from the patients’spermatozoa,validating the pathogenic nature of the mutation.This study provides direct evidence linking the AK7 gene to MMAF-associated asthenozoospermia in humans,expanding the mutational spectrum of AK7 and enhancing our understanding of the genetic basis of male infertility.展开更多
Objective:To evaluate the clinical effectiveness and safety of the Chinese medicine(CM)Qixiong Zhongzi Decoction(芪芎种子汤,QZD)in the treatment of patients with idiopathic asthenozoospermia.Methods:A total number of ...Objective:To evaluate the clinical effectiveness and safety of the Chinese medicine(CM)Qixiong Zhongzi Decoction(芪芎种子汤,QZD)in the treatment of patients with idiopathic asthenozoospermia.Methods:A total number of 66 patients with idiopathic asthenozoospermia were included and randomly divided into treatment and control groups by SAS-generated code from January 2015 to August 2016,33 patients in each group.Patients in the treatment group were administered with 150 m L of QZD twice a day,whereas those in the control group were given 1 g of levocarnitine oral liquid twice a day.The two groups received the indicated medication for 12 weeks and were then followed up for 4 weeks.The primary outcome was sperm motility,and the secondary therapeutic indices were sperm volume,density,pregnancy probability,and CM syndrome score.The comparison between groups was carried out at 4,8 and 12 weeks,respectively.The safety was determined before and after treatment.Results:(1)Drop-off:5 cases(7.58%)were lost after treatment(2 from the treatment group and 3 from the control group).(2)Primary outcomes:after 8-and 12-week treatment,the progressive sperms in the two groups were significantly higher than the baseline(all P<0.05);however,the treatment group showed greater improvement compared with the control group at 12-week treatment(22.7%±9.0%vs.14.1%±8.8%,P<0.05).The increasement of non-progressive grade sperms at both groups was observed at 8-and 12-week treatment with statistical difference(all P<0.05),however,the treatment group showed remarkable improvement compared with the control group at 12-week treatment(38.7%±14.1%vs.26.2%±15.4%,P<0.05).(3)Secondary outcomes:no significant statistical differences were found in semen volume and density(4,8,and 12-week treatment)and pregnancy probability of patients’wives(12-week treatment)between two groups(all P>0.05),however,the CM syndrome score of the treatment group significantly declined compared with baseline level at each time points(all P<0.05).(4)Safety:no obvious side reactions were found during the treatment in both groups.Conclusions:QZD could improve the progressive and non-progressive grade sperm in the treatment of idiopathic asthenozoospermia.It is safe with no obvious side effects.展开更多
基金supported by the National Key Research and Development Program of China(No.2022YFC2702702)National Natural Science Foundation of China(No.32270899 and No.32070842)+2 种基金the Natural Science Foundation of Jiangsu Province(No.BK20230004)Young and Middle-Aged Key Personnel Training Project of the Fujian Provincial Health Commission(2019-ZQN-62)Fujian Provincial Finance Project(BPB-TSX2021).
文摘The cause of asthenozoospermia(AZS)is not well understood because of its complexity and heterogeneity.Although some gene mutations have been identified as contributing factors,they are only responsible for a small number of cases.Radial spokes(RSs)are critical for adenosine triphosphate-driven flagellar beating and axoneme stability,which is essential for flagellum motility.In this study,we found novel compound heterozygous mutations in leucine-rich repeat-containing protein 23(LRRC23;c.1018C>T:p.Q340X and c.881_897 Del:p.R295Gfs*32)in a proband from a nonconsanguineous family with AZS and male infertility.Diff-Quik staining and scanning electron microscopy revealed no abnormal sperm morphology.Western blotting and immunofluorescence staining showed that these mutations suppressed LRRC23 expression in sperm flagella.Additionally,transmission electron microscopy showed the absence of RS3 in sperm flagella,which disrupts stability of the radial spoke complex and impairs motility.Following in vitro fertilization and embryo transfer,the proband’s spouse achieved successful pregnancy and delivered a healthy baby.In conclusion,our study indicates that two novel mutations in LRRC23 are associated with AZS,but successful fertility outcomes can be achieved by in vitro fertilization-embryo transfer techniques.
文摘Asthenozoospermia （AS） is a common cause of human male infertility. In one study, more than 80% of the samples from infertile men had reduced sperm motility. Seminal plasma is a mixture of secretions from the testis, epididymis and several male accessory glands, including the prostate, seminal vesicles and Cowper＇s gland. Studies have shown that seminal plasma contains proteins that are important for sperm motility. To further explore the pathophysiological character of AS, we separated the seminal plasma proteins from AS patients and healthy donors using sodium dodecyl sulfate polyacrylamide gel electrophoresis and in-gel digestion, and then subjected the proteins to liquid chromatography-mass spectrometry （LC-MS/MS） analysis. A total of 741 proteins were identified in the seminal plasma, with a false discovery rate of 3.3%. Using spectral counting, we found that 45 proteins were threefold upregulated and 56 proteins were threefold downregulated in the AS group when compared with the control. Most of these proteins originated from the epididymis and prostate. This study identified a rich source of biomarker candidates for male infertility and indicates that functional abnormalities of the epididymis and prostate can contribute to AS. We identified D J-1--a protein that has been shown elsewhere to be involved in the control of oxidative stress （OS）-as a downregulated protein in AS seminal plasma. The levels of D J-1 in AS seminal plasma were about half of those in the control samples. In addition, the levels of reactive oxygen species were 3.3-fold higher in the AS samples than in the controls. Taken together, these data suggest that downregulation of DJ-1 is involved in OS in semen, and therefore affects the quality of the semen.
文摘Human spermatozoa encounter an osmotic decrease from 330 to 290 mOsm I-z when passing through the female reproductive tract. We aimed to evaluate the role of chloride channels in volume regulation and sperm motility from patients with asthenozoospermia. Spermatozoa were purified using Percoll density gradients. Sperm volume was measured as the forward scatter signal using flow cytometry. Sperm motility was analyzed using computer-aided sperm analysis （CASA）. When transferred from an isotonic solution （330 mOsm I-z） to a hypotonic solution （290 mOsm I-Z）, cell volume was not changed in spermatozoa from normozoospermic men; but increased in those from asthenozoospermic samples. The addition of the chloride channel blockers, 4,4＇-diisothiocyanatostilbene-2,2＇- isulfonic acid （DIDS） or 5-nitro-2-（3-phenylpropylamino） benzoic acid （NPPB） to the hypotonic solution caused the normal spermatozoa to swell but did not increase the volume of those from the asthenozoospermic semen. DIDS and NPPB decreased sperm motility in both sets of semen samples. The inhibitory effect of NPPB on normal sperm motility was much stronger than on spermatozoa from the asthenozoospermic samples. Both sperm types expressed CIC-3 chloride channels, but the expression levels in the asthenozoospermic samples were much lower, especially in the neck and mid-piece areas. Spermatozoa from men with asthenozoospermia demonstrated lower volume regulating capacity, mobility, and CIC-3 expression levels （especially in the neck） than did normal spermatozoa. Thus, chloride channels play important roles in the regulation of sperm volume and motility and are downregulated in cases of asthenozoospermia.
基金supported by 2012 Independence Innovation Foundation of Huazhong University of Science and Technology(No.01-18-519003)
文摘A growing number of researches have shown that ouabain can regulate mammalian sperm function and male reproduction by modulating the sperm motility, capacitation and acrosome reaction in vitro. This study further examined the relationship between ouabain and asthenozoospermia. In this study, the rat was intraperitoneally injected with ouabain at different concentrations（low-dose ouabain group： 12.5 μg/kg body weight per day, and high-dose ouabain group： 25 μg/kg body weight per day） for 30 days to establish the asthenozoospermia model. The sperms from 60 males with normal fertility were incubated with ouabain of gradient concentrations（10-7–10-2mol/L） for 4 h. The sperm motility was evaluated under a microscope. Moreover, the endogenous ouabain（EO） level was determined in seminal plasma of mild or severe asthenozoospermia patients and males with normal fertility by competitive inhibition ELISA. The results showed that the sperm motility was significantly diminished in the rats treated with different concentrations of ouabain. The number of motile sperms（grades a and b） was decreased greatly in a time- and dose-dependent manner in 10-5–10-2mol/L ouabain groups（P0.01）, while no obvious change in sperm motility was observed in 10-7–10-6mol/L groups even for 4-h incubation（P0.05）. Furthermore, the EO level was significantly increased in asthenozoospermia patients as compared with that in males with normal fertility（25.27±1.71 μg/L in mild asthenozoospermia patients, 26.52±1.82 μg/L in severe asthenozoospermia patients, 19.31±1.45 μg/L in normal fertility men）（P0.01）. In conclusion, rat asthenozoospermia was successfully established by intraperitoneal injection of ouabain, and 10-5mol/L ouabain was sufficient enough to inhibit sperm motility in vitro. Moreover, EO, a normal constituent of seminal plasma, was highly expressed in asthenozoospermia males as compared with normal fertility ones.
基金This work was supported by the National Natural Science Foundation of China Grants （81430027 and 81671510 to FS 81501309 to GSW） and the National Basic Research Program of China （2014CB943100 to FS）.
文摘Spermatozoa are not mature until they transit the epididymis where they acquire motility and the ability to fertilize an egg through sequential modifications. The epididymis has three functional regions, caput, corpus, and cauda, and the luminal proteins of the epididymis play important roles in the above modifications. However, the proteins with differential enrichment between the caput and cauda are still largely unknown. To reveal the functions of the caput and cauda during sperm maturation, luminal proteins from caput and cauda of mice were analyzed by isobaric tag for relative and absolute quantitation （iTRAQ）. Overall, 128 differentially enriched proteins were found, of which 46 were caput enriched and 82 were cauda enriched. Bioinformatic analysis showed that lipid metabolism was active in the caput; while anion- and cation-binding activity and phosphorus and organophosphate metabolism were active in the cauda. A new epididymal luminal protein, the caput-enriched PDZ domain containing 1 （Pdzkl）, also named Na^＋/H^＋ exchange regulatory cofactor 3 （NHERF3）, which plays a critical role in cholesterol metabolism and carnitine transport, was found in the lipid metabolism. Western blotting and immunofluorescence analyses showed that Pdzkl was expressed in the epididymis but not in the testis, and localized at the middle piece of the sperm tail. Pdzkl protein level was also reduced in the spermatozoa in case of asthenozoospermic patients compared with that in normozoospermic men, suggesting that Pdzkl may participate in sperm maturation regulation and may be associated with male infertility. These results may provide new insights into the mechanisms of sperm maturation and male infertility.
文摘Idiopathic asthenozoospermia,a common factor in male infertility,is characterized by altered sperm motility function in fresh ejaculate.Although theβ-defensin 126(DEFB126)protein is associated with asthenozoospermia,DEFB126 gene polymorphisms have not been extensively studied.Therefore,the association between DEFB126 gene polymorphisms and asthenozoospermia requires further investigation.Screening was performed by semen analysis,karyotype analysis,and Y microdeletion detection,and 102 fertile men and 106 men with asthenozoospermia in Chengdu,China,were selected for DEFB126 gene sequence analyses.Seven nucleotide mutations and two nucleotide deletions in the DEFB126 gene were detected.rs11467417(317-318 del/del),rs11467497(163-166 wt/del),c.152T>C,and c.227A>G were significantly different between the control and asthenozoospermia groups,likely representing high-risk genetic factors for asthenozoospermia among males.DEFB126 expression was not observed in sperm with rs11467497 homozygous deletion and was unstable in sperm with rs11467417 homozygous deletion.The rs11467497 four-nucleotide deletion leads to truncation of DEFB126 at the carboxy-terminus,and the rs11467417 binucleotide deletion produces a non-stop messenger RNA(mRNA).The above deletions may be responsible for male hypofertility and infertility by reducing DEFB126 affinity to sperm surfaces.Based on in silico analysis,the amino acids 51M and 76K are located in the highly conserved domain;c.152T>C(M51T)and c.227A>G(K76R)are predicted to be damaging and capable of changing alternative splice,structural and posttranslational modification sites of the RNA,as well as the secondary structure,structural stability,and hydrophobicity of the protein,suggesting that these mutations are associated with asthenozoospermia.
基金National Natural Science Foundation of China(Grant No.81401259,U1603128)
文摘Asthenozoospermia is a common cause of male infertility and is characterized by reduced forward motility of spermatozoa. The pathogenesis of asthenozoospermia remains unclear. DJ-1 is a ubiquitous protein, widely expressed in the liver, skeletal muscle, kidney, brain and testis. It has been found correlated with many diseases including male infertility. This review presents the novel concept that the endogenous antioxidant properties of DJ-I in sperm is associated with asthenozoospermia. Thus, DJ-l is likely a new target for the treatment of asthenozoospermia.
文摘Male infertility contributes to 20%–70%of infertile couple cases worldwide.One of the key challenges in this area is asthenozoospermia or reduced sperm motility.A particular subset,known as isolated asthenozoospermia(iASZ),in which low motility occurs without abnormalities in sperm count or shape,often goes unnoticed and is not well understood.This narrative review attempts to compile the state of knowledge regarding the etiology,diagnosis,and treatment of iA SZ and to identify knowledge gaps that need further investigation with an emphasis on physiological,genetic,and molecular mechanisms.We conducted a focused literature search using PubMed and Web of Science,covering studies published between 2000 and 2024.We included articles that explored the structure,function,diagnosis,and treatment of iASZ.We find sperm motility is influenced by multiple factors,from structural components like mitochondria and the flagellum,to biochemical signals and genetic mutations.In men with iASZ,issues such as mitochondrial dysfunction,oxidative stress,or specific gene defects may impair motility.While routine semen analysis helps flag low motility,it often fails to explain why it occurs—highlighting the need for advanced tests like DNA fragmentation tests,genetic screening,and high-resolution imaging.As regards treatment,lifestyle changes,varicocele surgery,and antioxidants can offer some benefit.Assisted reproduction techniques,especially intracytoplasmic sperm injection(ICSI),remain central for achieving pregnancy when other options fail.iA SZ deserves more attention as a distinct and treatable cause of male infertility.By improving how we diagnose and manage this condition,supported by further research,we can offer better outcomes for affected couples hoping to conceive.
文摘Eissa et al.'s review warmly invites readers into the often-overlooked realm of isolated asthenozoospermia(iASZ),a condition marked by reduced sperm motility that affects 16%–24%of male infertility cases.With a nod to the authors’dedication,this work masterfully compiles insights into the physiological,genetic,and molecular underpinnings of iASZ,offering a clear guide to its etiology,diagnosis,and management.
文摘Objective:This study investigated the outcomes of microsurgical subinguinal varicocelectomy(MSV)on semen and hormonal parameters in cases with isolated sperm defects(oligozoospermia,asthenozoospermia,or teratozoospermia).Methods:A retrospective review of charts of patients who underwent MSV for clinically palpable varicocele between January 1,2011 and January 1,2019 at Hamad Medical Corporation was undertaken.All patients diagnosed with isolated oligozoospermia,asthenozoospermia,or teratozoospermia in the preoperative semen analysis were included.Men with multiple sperm defects,genetic abnormalities,azoospermia,history of genitourinary infection,exposure to chemotherapy or radiotherapy,or prior use of peri-operative fertility treatment were excluded.Data extracted from the electronic medical records included(collected before MSV and up to 6 months postoperatively):demographics(age),clinical data(fertility-related medical history and surgical interventions),family history(consanguinity and infertility),physical examination findings from general and local genital exam(varicocele side and grade),laboratory data such as semen analysis,sperm DNA fragmentation tests,and hormone levels(follicle-stimulating hormone,luteinizing hormone,total testosterone,estradiol,and prolactin),and imaging(scrotal color Doppler ultrasound).Results:A total of 331 patients with isolated sperm defects were included.Postoperatively,83.3%of patients showed an improvement in sperm concentration with a median increase of 7 millions/mL.Postoperatively,76.7%of isolated asthenozoospermic patients showed an improvement in total motility and 66.0%had an improvement in progressive motility with median increases of 15.0%and 7.5%,respectively.Postoperatively,70.0%of the teratozoospermic patients showed an improvement in normal sperm morphology with a median increase of 6%.No changes were observed in other semen or hormone parameters that were examined.Conclusion:MSV is a valid and effective treatment modality for patients with isolated sperm defects that significantly corrects their respective semen abnormality and improves their chances of natural conception.
基金supported by the National Key Research and Development Program of China(No.2021YFC2700202,No.2022YFA0806303,and No.2022YFC2702601)the Global Select Project of the Institute of Health and Medicine,Hefei Comprehensive National Science Center(DJK-LX-2022010)the Joint Fund for New Medicine of USTC(YD9100002034).
文摘Multiple morphological abnormalities of the flagella(MMAF)represent a severe form of sperm defects leading to asthenozoospermia and male infertility.In this study,we identified a novel homozygous splicing mutation(c.871-4 ACA>A)in the adenylate kinase 7(AK7)gene by whole-exome sequencing in infertile individuals.Spermatozoa from affected individuals exhibited typical MMAF characteristics,including coiled,bent,short,absent,and irregular flagella.Transmission electron microscopy analysis showed disorganized axonemal structure and abnormal mitochondrial sheets in sperm flagella.Immunofluorescence staining confirmed the absence of AK7 protein from the patients’spermatozoa,validating the pathogenic nature of the mutation.This study provides direct evidence linking the AK7 gene to MMAF-associated asthenozoospermia in humans,expanding the mutational spectrum of AK7 and enhancing our understanding of the genetic basis of male infertility.
基金Supported by the Fundamental Research Funds for the Central Public Welfare Research Institutes(No.ZZ070855)
文摘Objective:To evaluate the clinical effectiveness and safety of the Chinese medicine(CM)Qixiong Zhongzi Decoction(芪芎种子汤,QZD)in the treatment of patients with idiopathic asthenozoospermia.Methods:A total number of 66 patients with idiopathic asthenozoospermia were included and randomly divided into treatment and control groups by SAS-generated code from January 2015 to August 2016,33 patients in each group.Patients in the treatment group were administered with 150 m L of QZD twice a day,whereas those in the control group were given 1 g of levocarnitine oral liquid twice a day.The two groups received the indicated medication for 12 weeks and were then followed up for 4 weeks.The primary outcome was sperm motility,and the secondary therapeutic indices were sperm volume,density,pregnancy probability,and CM syndrome score.The comparison between groups was carried out at 4,8 and 12 weeks,respectively.The safety was determined before and after treatment.Results:(1)Drop-off:5 cases(7.58%)were lost after treatment(2 from the treatment group and 3 from the control group).(2)Primary outcomes:after 8-and 12-week treatment,the progressive sperms in the two groups were significantly higher than the baseline(all P<0.05);however,the treatment group showed greater improvement compared with the control group at 12-week treatment(22.7%±9.0%vs.14.1%±8.8%,P<0.05).The increasement of non-progressive grade sperms at both groups was observed at 8-and 12-week treatment with statistical difference(all P<0.05),however,the treatment group showed remarkable improvement compared with the control group at 12-week treatment(38.7%±14.1%vs.26.2%±15.4%,P<0.05).(3)Secondary outcomes:no significant statistical differences were found in semen volume and density(4,8,and 12-week treatment)and pregnancy probability of patients’wives(12-week treatment)between two groups(all P>0.05),however,the CM syndrome score of the treatment group significantly declined compared with baseline level at each time points(all P<0.05).(4)Safety:no obvious side reactions were found during the treatment in both groups.Conclusions:QZD could improve the progressive and non-progressive grade sperm in the treatment of idiopathic asthenozoospermia.It is safe with no obvious side effects.
