Aim： To develop a high-throughput multiplex, fast and simple assay to scan azoospermia factor （AZF） region microdeletions on the Y chromosome and establish the prevalence of Y chromosomal microdeletions in Chinese ...Aim： To develop a high-throughput multiplex, fast and simple assay to scan azoospermia factor （AZF） region microdeletions on the Y chromosome and establish the prevalence of Y chromosomal microdeletions in Chinese infertile males with azoospermia or oligozoospermia. Methods： In total, 178 infertile patients with azoospermia （nonobstructed）, 134 infertile patients with oligozoospermia as well as 40 fertile man controls were included in the present study. The samples were screened for AZF microdeletion using optimized multi-analyte suspension array （MASA） technology. Results： Of the 312 patients, 36 （11.5%） were found to have deletions in the AZF region. The rnicrodeletion frequency was 14% （25/178） in the azoospermia group and 8.2% （11/134） in the oligospermia group. Among 36 patients with microdeletions, 19 had deletions in the AZFc region, seven had deletions in AZFa and six had deletions in AZFb. In addition, four patients had both AZFb and AZFc deletions. No deletion in the AZF region was found in the 40 fertile controls. Conclusion： There is a high prevalence of Y chromosomal microdeletions in Chinese infertile males with azoospermia or oligozoospermia. The MASA technology, which has been established in the present study, provides a sensitive and high-throughput method for detecting the deletion of the Y chromosome. And the results suggest that genetic screening should be advised to infertile men before starting assisted reproductive treatments.展开更多
Aim： To assess for the first time the occurrence of Y chromosomal microdeletions and partial deletions of the Azoospermia Factor c （AZFc） region in Sri Lankan men and to correlate them with clinical parameters. Met...Aim： To assess for the first time the occurrence of Y chromosomal microdeletions and partial deletions of the Azoospermia Factor c （AZFc） region in Sri Lankan men and to correlate them with clinical parameters. Methods： In a retrospective study, we analyzed 96 infertile men （78 with non-obstructive azoospermia） and 87 controls with normal spermatogenesis. AZFa, AZFb, AZFc and partial deletions within the AZFc region were analyzed by multiplex polymerase chain reaction （PCR） according to established protocols. Results： No AZFa, AZFb or AZFc deletions were found in the control group. Seven patients in the group of infertile men were found to have deletions as following： one AZFa, two AZFc, two AZFbc and two AZFabc. The relative distribution of these patterns was significantly different compared with that found in the German population. Extension analysis confirmed that the deletions occurred according to the current pathogenic model, gr/gr deletions were found to be equally present both in the patients （n = 4） and in the control group （n = 4）. One b2/b3 deletion was found in the patient group. Conclusion： These results suggest that the frequency and pattern of microdeletions of the Y chromosome in Sri Lankan men are similar to those found in other populations and confirm that gr/gr deletions are not sufficient to cause spermatogenetic failure. （Asian J Androl 2006 Jan; 8： 39-44）展开更多
Spermatogenesis is regulated by several Y chromosome-specific genes located in a specific region of the long arm of the Y chromosome,the azoospermia factor region(AZF).AZF microdeletions are the main structural chromo...Spermatogenesis is regulated by several Y chromosome-specific genes located in a specific region of the long arm of the Y chromosome,the azoospermia factor region(AZF).AZF microdeletions are the main structural chromosomal abnormalities that cause male infertility.Assisted reproductive technology(ART)has been used to overcome natural fertilization barriers,allowing infertile couples to have children.However,these techniques increase the risk of vertical transmission of genetic defects.Despite widespread awareness of AZF microdeletions,the occurrence of de novo deletions and overexpression,as well as the expansion of AZF microdeletion vertical transmission,remains unknown.This review summarizes the mechanism of AZF microdeletion and the function of the candidate genes in the AZF region and their corresponding clinical phenotypes.Moreover,vertical transmission cases of AZF microdeletions,the impact of vertical inheritance on male fertility,and the prospective direction of research in this field are also outlined.展开更多
Objective To determine the incidence of azoospermia faetor （AZF） microdeletions of Y chromosome in male infertility and to investigate the mechanism of sex-determining region Y （SRY） in sex differentiation. Method...Objective To determine the incidence of azoospermia faetor （AZF） microdeletions of Y chromosome in male infertility and to investigate the mechanism of sex-determining region Y （SRY） in sex differentiation. Methods The mierodeletion of AZF was detected by multiplex polymerase chain reaction （PCR） using Y-chromosome specific sequence tagged sites （STSs）, and SRY was analyzed by PCR and sequencing. Results There were 100 cases with AZF microdeletion and the ratio of AZF microdeletion was 6.8% over all 1 474 cases. The ratios of AZF microdeletion of azoospermia group and severe oligozoospermia group were 9.0% and 7.1%, respectively, which was significantly different from oligozoospermia group （P〈 0. 05）. There were 67 cases with 5 STSs mierodeletion of sY152, sY239, sY243, sY254 and sY255. There were 20 cases with long fragment deletion more than 10 STSs, and the patterns of AZF microdeletion in other 13 cases were rare. In all 9 patients with disorders of sex differentiation, there were 6patients with SRY-absent and AZF-absent. There was no mutation of SRY gene by sequencing in other 3 patients with SRY-positive. Conclusion Deletions in AZF region of Y chromosome are specific with diagnoses with spermatogenesis disorder. Deletions of sY152, sY239, sY243, sY254 and sY255 occur the most frequently. SRY was an important candidate gene of testis-determining factor （TDF） gene.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
Aim: To determine the most common risk factors of male infertility in Mongolian men attending an infertility clinic. Methods: A prospective, case-control study was conducted in which 430 men were enrolled. All the men...Aim: To determine the most common risk factors of male infertility in Mongolian men attending an infertility clinic. Methods: A prospective, case-control study was conducted in which 430 men were enrolled. All the men had sought their first infertility evaluation between 1998-2002 in the State Research Center on Maternal Child Health, Ulaanbaatar, Mongolia. They were divided into two groups depending on the results of their semen analysis: 191 with abnormal semen and 239 with normal semen profile. Univariate and multivariate analyses were performed to determine any association between risk factors and semen abnormality. Results: Logistic regression analysis demonstrated that the testicular volume, a history of sexually transmitted infections (STI), epididymitis and testicular damage all have statistically significant associations with semen abnormality, when controlled for multiple risk factors. Adjusted odds ratios of 3.4 for mumps orchitis, 2.3 for other orchitis and 3.9 for testicular injury were found. Gonorrhoea, the most commonly reported STIs in this study, gave an adjusted odds ratio of 1.0 for having one or more sperm abnormality. An adjusted odds ratio for subjects with a history of other STIs was 2.7. However, as a predictor of azoospermia, STIs had very high odds ratio, being 5.6 in patients with gonorrhoea and 7.6 in patients with other STIs. Conclusion: A history of pathology involving testicular damage appeared to have the strongest impact on male infertility in Mongolia. STIs have less impact on semen quality except when complicated by orchitis, epididymitis and vasal obstruction.展开更多
Objective: To identify microdeletions in azoospermia factor(AZF) gene loci in patients with idiopathic azoospermia and severe oligozoospermia in Fujian. Methods: Molecular genetic detection method was used to detect m...Objective: To identify microdeletions in azoospermia factor(AZF) gene loci in patients with idiopathic azoospermia and severe oligozoospermia in Fujian. Methods: Molecular genetic detection method was used to detect microdeletion at the AZFa, AZFb, AZFc /DAZ,SRY region of Y chromosome in 47 azoospermia and 4 severe oligozoospermia patients. Genomic DNA was extracted from peripheral blood. The sequence tagged site (STS) primers tested in each cases were sY84(AZFa), sY 143(AZFb) sY254(AZFc).SRY region of Y chromosome for control. The PCR products were analyzed on a 2.0% agarose gel. Results: Microdeletions of the Y-chromosomal AZF loci were revealed in 18(35.3%,18/51) of 51 patients with idiopathic azoospermia and severe oligozoospermia. AZFa deletion was found in four (7.8%) patients, AZF b in five (9.8%) patients, AZF c in four (7.8%) patients. AZF a+b in one(1.9%)patient, AZF b+c in two (3.9%) patients, AZF a+b+c in two (3.9%)patients respectively. No deletion of SRY region was found. No deletion of AZF a, AZF b, AZF c/DAZ,SRY regions was found in five fertile male who had at least one or more children. Conclusions: Microdeletions on AZF/DAZ gene loci were major genetics defects leading to azoospermia and severe oligozoospermia in male idiopathic infertility in Fujian. It is necessary to have genetic counseling and carry out microdeletion detection on AZF/DAZ gene loci before performing intracytoplasmic sperm injection (ICSI).展开更多
文摘Aim： To develop a high-throughput multiplex, fast and simple assay to scan azoospermia factor （AZF） region microdeletions on the Y chromosome and establish the prevalence of Y chromosomal microdeletions in Chinese infertile males with azoospermia or oligozoospermia. Methods： In total, 178 infertile patients with azoospermia （nonobstructed）, 134 infertile patients with oligozoospermia as well as 40 fertile man controls were included in the present study. The samples were screened for AZF microdeletion using optimized multi-analyte suspension array （MASA） technology. Results： Of the 312 patients, 36 （11.5%） were found to have deletions in the AZF region. The rnicrodeletion frequency was 14% （25/178） in the azoospermia group and 8.2% （11/134） in the oligospermia group. Among 36 patients with microdeletions, 19 had deletions in the AZFc region, seven had deletions in AZFa and six had deletions in AZFb. In addition, four patients had both AZFb and AZFc deletions. No deletion in the AZF region was found in the 40 fertile controls. Conclusion： There is a high prevalence of Y chromosomal microdeletions in Chinese infertile males with azoospermia or oligozoospermia. The MASA technology, which has been established in the present study, provides a sensitive and high-throughput method for detecting the deletion of the Y chromosome. And the results suggest that genetic screening should be advised to infertile men before starting assisted reproductive treatments.
文摘Aim： To assess for the first time the occurrence of Y chromosomal microdeletions and partial deletions of the Azoospermia Factor c （AZFc） region in Sri Lankan men and to correlate them with clinical parameters. Methods： In a retrospective study, we analyzed 96 infertile men （78 with non-obstructive azoospermia） and 87 controls with normal spermatogenesis. AZFa, AZFb, AZFc and partial deletions within the AZFc region were analyzed by multiplex polymerase chain reaction （PCR） according to established protocols. Results： No AZFa, AZFb or AZFc deletions were found in the control group. Seven patients in the group of infertile men were found to have deletions as following： one AZFa, two AZFc, two AZFbc and two AZFabc. The relative distribution of these patterns was significantly different compared with that found in the German population. Extension analysis confirmed that the deletions occurred according to the current pathogenic model, gr/gr deletions were found to be equally present both in the patients （n = 4） and in the control group （n = 4）. One b2/b3 deletion was found in the patient group. Conclusion： These results suggest that the frequency and pattern of microdeletions of the Y chromosome in Sri Lankan men are similar to those found in other populations and confirm that gr/gr deletions are not sufficient to cause spermatogenetic failure. （Asian J Androl 2006 Jan; 8： 39-44）
基金supported by National Natural Science Foundation of China (No.81901535 and No.82071698)the National Key Research&Developmental Program of China (No.2021YFC2700203)Natural Science Foundation of Beijing Municipality (No.7222208).
文摘Spermatogenesis is regulated by several Y chromosome-specific genes located in a specific region of the long arm of the Y chromosome,the azoospermia factor region(AZF).AZF microdeletions are the main structural chromosomal abnormalities that cause male infertility.Assisted reproductive technology(ART)has been used to overcome natural fertilization barriers,allowing infertile couples to have children.However,these techniques increase the risk of vertical transmission of genetic defects.Despite widespread awareness of AZF microdeletions,the occurrence of de novo deletions and overexpression,as well as the expansion of AZF microdeletion vertical transmission,remains unknown.This review summarizes the mechanism of AZF microdeletion and the function of the candidate genes in the AZF region and their corresponding clinical phenotypes.Moreover,vertical transmission cases of AZF microdeletions,the impact of vertical inheritance on male fertility,and the prospective direction of research in this field are also outlined.
文摘Objective To determine the incidence of azoospermia faetor （AZF） microdeletions of Y chromosome in male infertility and to investigate the mechanism of sex-determining region Y （SRY） in sex differentiation. Methods The mierodeletion of AZF was detected by multiplex polymerase chain reaction （PCR） using Y-chromosome specific sequence tagged sites （STSs）, and SRY was analyzed by PCR and sequencing. Results There were 100 cases with AZF microdeletion and the ratio of AZF microdeletion was 6.8% over all 1 474 cases. The ratios of AZF microdeletion of azoospermia group and severe oligozoospermia group were 9.0% and 7.1%, respectively, which was significantly different from oligozoospermia group （P〈 0. 05）. There were 67 cases with 5 STSs mierodeletion of sY152, sY239, sY243, sY254 and sY255. There were 20 cases with long fragment deletion more than 10 STSs, and the patterns of AZF microdeletion in other 13 cases were rare. In all 9 patients with disorders of sex differentiation, there were 6patients with SRY-absent and AZF-absent. There was no mutation of SRY gene by sequencing in other 3 patients with SRY-positive. Conclusion Deletions in AZF region of Y chromosome are specific with diagnoses with spermatogenesis disorder. Deletions of sY152, sY239, sY243, sY254 and sY255 occur the most frequently. SRY was an important candidate gene of testis-determining factor （TDF） gene.
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.
文摘Aim: To determine the most common risk factors of male infertility in Mongolian men attending an infertility clinic. Methods: A prospective, case-control study was conducted in which 430 men were enrolled. All the men had sought their first infertility evaluation between 1998-2002 in the State Research Center on Maternal Child Health, Ulaanbaatar, Mongolia. They were divided into two groups depending on the results of their semen analysis: 191 with abnormal semen and 239 with normal semen profile. Univariate and multivariate analyses were performed to determine any association between risk factors and semen abnormality. Results: Logistic regression analysis demonstrated that the testicular volume, a history of sexually transmitted infections (STI), epididymitis and testicular damage all have statistically significant associations with semen abnormality, when controlled for multiple risk factors. Adjusted odds ratios of 3.4 for mumps orchitis, 2.3 for other orchitis and 3.9 for testicular injury were found. Gonorrhoea, the most commonly reported STIs in this study, gave an adjusted odds ratio of 1.0 for having one or more sperm abnormality. An adjusted odds ratio for subjects with a history of other STIs was 2.7. However, as a predictor of azoospermia, STIs had very high odds ratio, being 5.6 in patients with gonorrhoea and 7.6 in patients with other STIs. Conclusion: A history of pathology involving testicular damage appeared to have the strongest impact on male infertility in Mongolia. STIs have less impact on semen quality except when complicated by orchitis, epididymitis and vasal obstruction.
文摘Objective: To identify microdeletions in azoospermia factor(AZF) gene loci in patients with idiopathic azoospermia and severe oligozoospermia in Fujian. Methods: Molecular genetic detection method was used to detect microdeletion at the AZFa, AZFb, AZFc /DAZ,SRY region of Y chromosome in 47 azoospermia and 4 severe oligozoospermia patients. Genomic DNA was extracted from peripheral blood. The sequence tagged site (STS) primers tested in each cases were sY84(AZFa), sY 143(AZFb) sY254(AZFc).SRY region of Y chromosome for control. The PCR products were analyzed on a 2.0% agarose gel. Results: Microdeletions of the Y-chromosomal AZF loci were revealed in 18(35.3%,18/51) of 51 patients with idiopathic azoospermia and severe oligozoospermia. AZFa deletion was found in four (7.8%) patients, AZF b in five (9.8%) patients, AZF c in four (7.8%) patients. AZF a+b in one(1.9%)patient, AZF b+c in two (3.9%) patients, AZF a+b+c in two (3.9%)patients respectively. No deletion of SRY region was found. No deletion of AZF a, AZF b, AZF c/DAZ,SRY regions was found in five fertile male who had at least one or more children. Conclusions: Microdeletions on AZF/DAZ gene loci were major genetics defects leading to azoospermia and severe oligozoospermia in male idiopathic infertility in Fujian. It is necessary to have genetic counseling and carry out microdeletion detection on AZF/DAZ gene loci before performing intracytoplasmic sperm injection (ICSI).
文摘为评估定量荧光PCR(Quantitative fluorescent polymerase chain reaction,QF-PCR)技术在快速筛查无精子症因子(Azoospermia factor,AZF)微缺失中的应用,文章对1218例非梗阻性无精子症、少精子症的男性不育患者,采用多重QF-PCR结合毛细管电泳技术,检测Y染色体长臂AZF区9个序列标签位点(Sequence tagged site,STS)以及性染色体短臂的AMEL(Amelogenin)和SRY(Sex-determining region of Y chromosome)位点,辅以常规染色体G显带方法进行核型分析。结果显示,1218例患者中105例可见AZF区微缺失(8.62%),其中AZFc区缺失(67.62%)最常见,其次为AZFb,c区缺失(20.95%);AZFb区缺失(7.62%)和AZFa区缺失(3.81%)则较少见;另有5例患者为AZFa,b,c区缺失合并AMEL-Y缺失,提示可能缺少Y染色体,经核型分析验证为46,XX(性反转)。105例AZF区微缺失患者的染色体核型分析显示染色体异常16例,其中"Yqh-"12例。根据AMEL-X/AMEL-Y比值,可见1218例患者中86例可能存在性染色体异常,经核型分析验证,68例为性染色体非整倍体。多重QF-PCR技术,一个反应即能检测样本的多个位点,并可提示性染色体是否存在异常,有助于男性不育患者尽早明确病因,也为后续的检查和治疗提供依据。
