Teratozoospermia with cephalic defects is one of the most severe types of sperm defects known to date.While several monogenic factors are linked to cephalic abnormalities,such as globozoospermia and macrozoospermia,th...Teratozoospermia with cephalic defects is one of the most severe types of sperm defects known to date.While several monogenic factors are linked to cephalic abnormalities,such as globozoospermia and macrozoospermia,the genetic cause of vacuolated spermatozoa remains inadequately described.Here,we analyzed whole-exome sequencing(WES)data for an individual from a consanguineous family with severely vacuolated spermatozoa.The analysis revealed a novel homozygous c.520A>G(p.Thr174Ala)variant in the archaelysin family metallopeptidase 2(AMZ2),a gene that encodes a zinc metalloprotease previously shown to be highly expressed in the testes and sperm.Multiple algorithms predicted this variant to be a damaging mutation.Consistent with an autosomal recessive mode of inheritance,this variant was inherited from heterozygous parental carriers.To investigate the potential pathogenicity of the identified variant,we compared the AMZ2 expression in sperm cells from the patient with the AMZ2 variant and from a healthy control.Immunoblot analysis revealed that the homozygous missense variant in AMZ2 abolished AMZ2 expression in the spermatozoa.Our findings reveal a candidate causative gene for vacuolated spermatozoa.展开更多
Teratozoospermia is an infertility issue that affects a significant number of couples of reproductive age. One of the potential causes contributing to the global decline in seminal quality includes factors such as die...Teratozoospermia is an infertility issue that affects a significant number of couples of reproductive age. One of the potential causes contributing to the global decline in seminal quality includes factors such as diet, alcohol and tobacco consumption, high levels of stress, and environmental influences. This underscores the need to preserve the fertility of these patients through cryopreservation techniques. In this review, we explore the latest methods for freezing seminal samples, highlighting their advancements and advantages in addressing the challenge of perpetuating animal species, particularly in the context of human infertility.展开更多
Teratozoospermia is usually associated with defective spermiogenesis and is a disorder with considerable genetic heterogeneity. Although previous studies have identified several teratozoospermia-associated genes, the ...Teratozoospermia is usually associated with defective spermiogenesis and is a disorder with considerable genetic heterogeneity. Although previous studies have identified several teratozoospermia-associated genes, the etiology remains unknown for a majority of affected men. Here, we identified a homozygous missense mutation and a compound heterozygous mutation of CCIN in patients suffering from teratozoospermia. CCIN encodes the cytoskeletal protein Calicin that is involved in the formation and maintenance of the highly regular organization of the calyx of mammalian spermatozoa, and has been proposed to play a role in sperm head structure remodeling during the process of spermiogenesis. Our morphological and ultrastructural analyses of the spermatozoa obtained from all three men harboring deleterious CCIN mutants reveal severe head malformation. Further immunofluorescence assays unveil markedly reduced levels of Calicin in spermatozoa. These patient phenotypes are successfully recapitulated in mouse models expressing the disease-associated variants, confirming the role of Calicin in male fertility.Notably, all mutant spermatozoa from mice and human patients fail to adhere to the zona mass, which likely is the major mechanistic reason for CCIN-mutant sperm-derived infertility. Finally, the use of intracytoplasmic sperm injections(ICSI) successfully makes mutated mice and two couples with CCIN variants have healthy offspring. Taken together, our findings identify the role of Calicin in sperm head shaping and male fertility, providing important guidance for genetic counseling and assisted reproduction treatments.展开更多
Oligo-astheno-teratozoospermia（OAT） which perplexes doctors and patients due to its complicated etiology, atypical symptoms and poor clinical efficacy, is a general term for the three pathological states of abnormal...Oligo-astheno-teratozoospermia（OAT） which perplexes doctors and patients due to its complicated etiology, atypical symptoms and poor clinical efficacy, is a general term for the three pathological states of abnormal semen. OAT is the main factor of male infertility. It is also a hot and difficult point in present studies. Empiric drug is the most popular treatment of this disease in the modern medicine. Chinese medicine（CM） is one of the main methods for the treatment of this disease, and it has certain clinical effect. The author believes that the use of modern medical technology to make the diagnosis as clear as possible is the key to treat OAT. The combination of syndrome and disease differentiation is the main mode in the treatment of OAT. Microscopic syndrome differentiation and macroscopic evidence embodies the basic principle of ＂Si Wai Chuai Nei＂ and broadens the perspective of CM syndrome differentiation. Classification and treatment are basic methods for the treatment of OAT. The treatment should not be limited to the Shen（Kidney）, instead it should focus on the whole body condition. At different stages, the treatment should also pay attention to strengthening the Pi（Spleen）, nourishing the Gan（Liver） and promoting blood circulation. Complementing Chinese and Western medicine, and highlighting the characteristics and advantages of CM treatment, have a great guiding value for the treatment of OAT.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
目的:利用生物信息学分析筛选畸形精子症与氧化应激相关的差异表达基因(differentially expressed genes related to oxidative stress,OS-DEG)并进行候选中药材预测。方法:从GEO(Gene Expression Omnibus)数据库查找GSE6969基因表达图...目的:利用生物信息学分析筛选畸形精子症与氧化应激相关的差异表达基因(differentially expressed genes related to oxidative stress,OS-DEG)并进行候选中药材预测。方法:从GEO(Gene Expression Omnibus)数据库查找GSE6969基因表达图谱,筛选差异表达基因后与GeneCards数据库中OS-DEG取交集,通过基因本体(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析以及蛋白质-蛋白质互作(protein-protein interaction,PPI)网络筛选关键通路和基因,在中医药百科全书数据库(The Encyclopedia of Traditional Chinese Medicine,ETCM)中查找关键基因的候选中药材药物。结果:通过差异分析共发现261个OS-DEG,利用Cytoscape筛选出PTEN、JUN、糖原合成酶激酶3β(glycogen synthase kinase 3β,GSK3β)、超氧化物歧化酶2(superoxide dismutase 2,SOD2)等关键基因。预测的候选靶向中药材包括马齿苋、北沙参、半夏、马鞭草、丹参和白附子等。结论:可利用生物信息学分析筛选畸形精子症氧化应激相关的基因,为探讨中医药治疗畸形精子症提供新的见解。展开更多
基金This study was supported by the National Natural Science Foundation of China(No.32200485)the University Synergy Innovation Program of Anhui Province(GXXT-2021-071)Shanghai Municipal Science and Technology Major Project(No.2017SHZDZX01).
文摘Teratozoospermia with cephalic defects is one of the most severe types of sperm defects known to date.While several monogenic factors are linked to cephalic abnormalities,such as globozoospermia and macrozoospermia,the genetic cause of vacuolated spermatozoa remains inadequately described.Here,we analyzed whole-exome sequencing(WES)data for an individual from a consanguineous family with severely vacuolated spermatozoa.The analysis revealed a novel homozygous c.520A>G(p.Thr174Ala)variant in the archaelysin family metallopeptidase 2(AMZ2),a gene that encodes a zinc metalloprotease previously shown to be highly expressed in the testes and sperm.Multiple algorithms predicted this variant to be a damaging mutation.Consistent with an autosomal recessive mode of inheritance,this variant was inherited from heterozygous parental carriers.To investigate the potential pathogenicity of the identified variant,we compared the AMZ2 expression in sperm cells from the patient with the AMZ2 variant and from a healthy control.Immunoblot analysis revealed that the homozygous missense variant in AMZ2 abolished AMZ2 expression in the spermatozoa.Our findings reveal a candidate causative gene for vacuolated spermatozoa.
文摘Teratozoospermia is an infertility issue that affects a significant number of couples of reproductive age. One of the potential causes contributing to the global decline in seminal quality includes factors such as diet, alcohol and tobacco consumption, high levels of stress, and environmental influences. This underscores the need to preserve the fertility of these patients through cryopreservation techniques. In this review, we explore the latest methods for freezing seminal samples, highlighting their advancements and advantages in addressing the challenge of perpetuating animal species, particularly in the context of human infertility.
基金supported by the National Natural Science Foundation of China(31930063,81771533,81901531,31971137,and 81871163)the National Key Research and Development Program of China(2018YFC2000102,2018YFA0107004,and 2018YFC1003000)+2 种基金the Shanghai Municipal Health Commission and Collaborative Innovation Cluster Project(2019CXJQ01)SHIPM-pi Fund(JY201801)SHIPM-mu Fund(JC201802)。
文摘Teratozoospermia is usually associated with defective spermiogenesis and is a disorder with considerable genetic heterogeneity. Although previous studies have identified several teratozoospermia-associated genes, the etiology remains unknown for a majority of affected men. Here, we identified a homozygous missense mutation and a compound heterozygous mutation of CCIN in patients suffering from teratozoospermia. CCIN encodes the cytoskeletal protein Calicin that is involved in the formation and maintenance of the highly regular organization of the calyx of mammalian spermatozoa, and has been proposed to play a role in sperm head structure remodeling during the process of spermiogenesis. Our morphological and ultrastructural analyses of the spermatozoa obtained from all three men harboring deleterious CCIN mutants reveal severe head malformation. Further immunofluorescence assays unveil markedly reduced levels of Calicin in spermatozoa. These patient phenotypes are successfully recapitulated in mouse models expressing the disease-associated variants, confirming the role of Calicin in male fertility.Notably, all mutant spermatozoa from mice and human patients fail to adhere to the zona mass, which likely is the major mechanistic reason for CCIN-mutant sperm-derived infertility. Finally, the use of intracytoplasmic sperm injections(ICSI) successfully makes mutated mice and two couples with CCIN variants have healthy offspring. Taken together, our findings identify the role of Calicin in sperm head shaping and male fertility, providing important guidance for genetic counseling and assisted reproduction treatments.
基金Supported by the National Natural Science Foundation of China(No.81473527)
文摘Oligo-astheno-teratozoospermia（OAT） which perplexes doctors and patients due to its complicated etiology, atypical symptoms and poor clinical efficacy, is a general term for the three pathological states of abnormal semen. OAT is the main factor of male infertility. It is also a hot and difficult point in present studies. Empiric drug is the most popular treatment of this disease in the modern medicine. Chinese medicine（CM） is one of the main methods for the treatment of this disease, and it has certain clinical effect. The author believes that the use of modern medical technology to make the diagnosis as clear as possible is the key to treat OAT. The combination of syndrome and disease differentiation is the main mode in the treatment of OAT. Microscopic syndrome differentiation and macroscopic evidence embodies the basic principle of ＂Si Wai Chuai Nei＂ and broadens the perspective of CM syndrome differentiation. Classification and treatment are basic methods for the treatment of OAT. The treatment should not be limited to the Shen（Kidney）, instead it should focus on the whole body condition. At different stages, the treatment should also pay attention to strengthening the Pi（Spleen）, nourishing the Gan（Liver） and promoting blood circulation. Complementing Chinese and Western medicine, and highlighting the characteristics and advantages of CM treatment, have a great guiding value for the treatment of OAT.
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.
文摘目的:利用生物信息学分析筛选畸形精子症与氧化应激相关的差异表达基因(differentially expressed genes related to oxidative stress,OS-DEG)并进行候选中药材预测。方法:从GEO(Gene Expression Omnibus)数据库查找GSE6969基因表达图谱,筛选差异表达基因后与GeneCards数据库中OS-DEG取交集,通过基因本体(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析以及蛋白质-蛋白质互作(protein-protein interaction,PPI)网络筛选关键通路和基因,在中医药百科全书数据库(The Encyclopedia of Traditional Chinese Medicine,ETCM)中查找关键基因的候选中药材药物。结果:通过差异分析共发现261个OS-DEG,利用Cytoscape筛选出PTEN、JUN、糖原合成酶激酶3β(glycogen synthase kinase 3β,GSK3β)、超氧化物歧化酶2(superoxide dismutase 2,SOD2)等关键基因。预测的候选靶向中药材包括马齿苋、北沙参、半夏、马鞭草、丹参和白附子等。结论:可利用生物信息学分析筛选畸形精子症氧化应激相关的基因,为探讨中医药治疗畸形精子症提供新的见解。
