Objective The protein interacting with C kinase 1(PICK1)plays a critical role in vesicle trafficking,and its deficiency in sperm cells results in abnormal vesicle trafficking from Golgi to acrosome,which eventually di...Objective The protein interacting with C kinase 1(PICK1)plays a critical role in vesicle trafficking,and its deficiency in sperm cells results in abnormal vesicle trafficking from Golgi to acrosome,which eventually disrupts acrosome formation and leads to male infertility.Methods An azoospermia sample was filtered,and the laboratory detection and clinical phenotype indicated typical azoospermia in the patient.We sequenced all of the exons in the PICK1 gene and found that there was a novel homozygous variant in the PICK1 gene,c.364delA(p.Lys122SerfsX8),and this protein structure truncating variant seriously affected the biological function.Then we constructed a PICK1 knockout mouse model using clustered regularly interspaced short palindromic repeat cutting technology(CRISPRc).Results The sperm from PICK1 knockout mice showed acrosome and nucleus abnormalities,as well as dysfunctional mitochondrial sheath formation.Both the total sperm and motility sperm counts were decreased in the PICK1 knockout mice compared to wild-type mice.Moreover,the mitochondrial dysfunction was verified in the mice.These defects in the male PICK1 knockout mice may have eventually led to complete infertility.Conclusion The c.364delA novel variant in the PICK1 gene associated with clinical infertility,and pathogenic variants in the PICK1 may cause azoospermia or asthenospermia by impairing mitochondrial function in both mice and humans.展开更多
45,X/46,XY染色体嵌合是临床上比较少见的疾病,具有这种嵌合核型的患者可表现为男性或者女性外观,临床特征相似于特纳综合征(Turner syndrome,Turner综合征),但症状轻于Turner综合征。报告1例因不育就诊的男性表型患者,经G显带染色体核...45,X/46,XY染色体嵌合是临床上比较少见的疾病,具有这种嵌合核型的患者可表现为男性或者女性外观,临床特征相似于特纳综合征(Turner syndrome,Turner综合征),但症状轻于Turner综合征。报告1例因不育就诊的男性表型患者,经G显带染色体核型分析和全基因组拷贝数变异(copy number variation,CNV)技术分析患者外周血提取的DNA,染色体核型诊断为45,X/46,XY嵌合型,外周血淋巴细胞染色体核型共分析50个染色体核型,核型诊断结果为45,X[27]/46,XY[23],全基因组CNV检测结果为-(mosaic)(Y)(64%),Y染色体微缺失检测结果为未见明显异常。45,X/46,XY染色体嵌合型男性表型案例较少,本例患者身材矮小,生殖器畸形,是临床表型较轻的男性表型患者。展开更多
Aim： To investigate the possible causes of oligozoospermia and azoospermia in infertile Thai men, and to find the frequencies of Y chromosome microdeletions and cytogenetic abnormalities in this group. Methods： From...Aim： To investigate the possible causes of oligozoospermia and azoospermia in infertile Thai men, and to find the frequencies of Y chromosome microdeletions and cytogenetic abnormalities in this group. Methods： From June 2003 to November 2005, 50 azoospermic and 80 oligozoospermic men were enrolled in the study. A detailed history was taken for each man, followed by general and genital examinations. Y chromosome microdeletions were detected by multiplex polymerase chain reaction （PCR） using 11 gene-specific primers that covered all three regions of the azoospermic factor （AZFa, AZFb and AZFc）. Fifty men with normal semen analysis were also studied. Karyotyping was done with the standard G- and Q-banding. Serum concentrations of follicle stimulating hormone （FSH）, luteinizing hormone （LH）, prolactin （PRL） and testosterone were measured by electrochemiluminescence immunoassays （ECLIA）. Results： Azoospermia and oligozoospermia could be explained by previous orchitis in 22.3%, former bilateral cryptorchidism in 19.2%, abnormal karyotypes in 4.6% and Y chromosome microdeletions in 3.8% of the subjects. The most frequent deletions were in the AZFc region （50%）, followed by AZFb （33%） and AZFbc （17%）. No significant difference was detected in hormonal profiles of infertile men, with or without microdeletions. Conclusion： The frequencies of Y chromosome microdeletions and cytogenetic abnormalities in oligozoospermic and azoospermic Thai men are comparable with similarly infertile men from other Asian and Western countries.展开更多
Aim: To review the accumulated 30 patients with different area of Y chromosome microdeletions, focusing on their correlation with the clinical and pathological findings. Methods: A total of 334 consecutive infertile m...Aim: To review the accumulated 30 patients with different area of Y chromosome microdeletions, focusing on their correlation with the clinical and pathological findings. Methods: A total of 334 consecutive infertile men with azoospermia (218 patients) and severe oligoasthenospermia (116 patients) were screened. Complete physical and endocrinological examinations, general chromosome study and multiplex polymerase chain reaction assay to evaluate the Y chromosome microdeletion were performed. Ten patients received testicular biopsy. Then the clinical and pathological findings were analyzed with reference to the areas of Y chromosome microdeletion. Results: There is a decline of the percentage of sperm appearing in semen in the group that the gene deletion region from AZFc to AZFb. The clinical evidence of the impairment (decreased testicular size and elevated serum FSH) is also relevantly aggravated in this group. However, the pathology of testicular biopsy specimen was poorly correlated with the different deletion areas of the Y chromosome, which may be due to the limited number of specimens. Conclusion: The clinical correlation of spermatogenic impairment to the different AZF deletion regions may provide the information for the infertile couples in pre-treatment counseling.展开更多
基金supported by grants from Zhejiang Provincial Natural Science Foundation of China(No.LQ21H200007)National Natural Science Foundation of China(No.82202605,No.81772664 and No.82172363)+1 种基金Zhejiang Provincial People’s Hospital Excellent Scientific Research Start-up Fundation of China(No.ZRY2019C008)Hangzhou Medical College Fundamental Scientific Research Project of China(No.KYQN202116).
文摘Objective The protein interacting with C kinase 1(PICK1)plays a critical role in vesicle trafficking,and its deficiency in sperm cells results in abnormal vesicle trafficking from Golgi to acrosome,which eventually disrupts acrosome formation and leads to male infertility.Methods An azoospermia sample was filtered,and the laboratory detection and clinical phenotype indicated typical azoospermia in the patient.We sequenced all of the exons in the PICK1 gene and found that there was a novel homozygous variant in the PICK1 gene,c.364delA(p.Lys122SerfsX8),and this protein structure truncating variant seriously affected the biological function.Then we constructed a PICK1 knockout mouse model using clustered regularly interspaced short palindromic repeat cutting technology(CRISPRc).Results The sperm from PICK1 knockout mice showed acrosome and nucleus abnormalities,as well as dysfunctional mitochondrial sheath formation.Both the total sperm and motility sperm counts were decreased in the PICK1 knockout mice compared to wild-type mice.Moreover,the mitochondrial dysfunction was verified in the mice.These defects in the male PICK1 knockout mice may have eventually led to complete infertility.Conclusion The c.364delA novel variant in the PICK1 gene associated with clinical infertility,and pathogenic variants in the PICK1 may cause azoospermia or asthenospermia by impairing mitochondrial function in both mice and humans.
文摘45,X/46,XY染色体嵌合是临床上比较少见的疾病,具有这种嵌合核型的患者可表现为男性或者女性外观,临床特征相似于特纳综合征(Turner syndrome,Turner综合征),但症状轻于Turner综合征。报告1例因不育就诊的男性表型患者,经G显带染色体核型分析和全基因组拷贝数变异(copy number variation,CNV)技术分析患者外周血提取的DNA,染色体核型诊断为45,X/46,XY嵌合型,外周血淋巴细胞染色体核型共分析50个染色体核型,核型诊断结果为45,X[27]/46,XY[23],全基因组CNV检测结果为-(mosaic)(Y)(64%),Y染色体微缺失检测结果为未见明显异常。45,X/46,XY染色体嵌合型男性表型案例较少,本例患者身材矮小,生殖器畸形,是临床表型较轻的男性表型患者。
文摘Aim： To investigate the possible causes of oligozoospermia and azoospermia in infertile Thai men, and to find the frequencies of Y chromosome microdeletions and cytogenetic abnormalities in this group. Methods： From June 2003 to November 2005, 50 azoospermic and 80 oligozoospermic men were enrolled in the study. A detailed history was taken for each man, followed by general and genital examinations. Y chromosome microdeletions were detected by multiplex polymerase chain reaction （PCR） using 11 gene-specific primers that covered all three regions of the azoospermic factor （AZFa, AZFb and AZFc）. Fifty men with normal semen analysis were also studied. Karyotyping was done with the standard G- and Q-banding. Serum concentrations of follicle stimulating hormone （FSH）, luteinizing hormone （LH）, prolactin （PRL） and testosterone were measured by electrochemiluminescence immunoassays （ECLIA）. Results： Azoospermia and oligozoospermia could be explained by previous orchitis in 22.3%, former bilateral cryptorchidism in 19.2%, abnormal karyotypes in 4.6% and Y chromosome microdeletions in 3.8% of the subjects. The most frequent deletions were in the AZFc region （50%）, followed by AZFb （33%） and AZFbc （17%）. No significant difference was detected in hormonal profiles of infertile men, with or without microdeletions. Conclusion： The frequencies of Y chromosome microdeletions and cytogenetic abnormalities in oligozoospermic and azoospermic Thai men are comparable with similarly infertile men from other Asian and Western countries.
文摘Aim: To review the accumulated 30 patients with different area of Y chromosome microdeletions, focusing on their correlation with the clinical and pathological findings. Methods: A total of 334 consecutive infertile men with azoospermia (218 patients) and severe oligoasthenospermia (116 patients) were screened. Complete physical and endocrinological examinations, general chromosome study and multiplex polymerase chain reaction assay to evaluate the Y chromosome microdeletion were performed. Ten patients received testicular biopsy. Then the clinical and pathological findings were analyzed with reference to the areas of Y chromosome microdeletion. Results: There is a decline of the percentage of sperm appearing in semen in the group that the gene deletion region from AZFc to AZFb. The clinical evidence of the impairment (decreased testicular size and elevated serum FSH) is also relevantly aggravated in this group. However, the pathology of testicular biopsy specimen was poorly correlated with the different deletion areas of the Y chromosome, which may be due to the limited number of specimens. Conclusion: The clinical correlation of spermatogenic impairment to the different AZF deletion regions may provide the information for the infertile couples in pre-treatment counseling.
