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
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 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
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 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
Aim: To study the occurrence of Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome (KFS). Methods: Blood and semen samples were collected from azoospermic patients with KFS (n = 14)...Aim: To study the occurrence of Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome (KFS). Methods: Blood and semen samples were collected from azoospermic patients with KFS (n = 14) and a control group of men of proven fertility (n = 13). Semen analysis was done according to World Health Organization (WHO) guidelines. Blood samples were processed for karyotyping, fluorescent in situ hybridization (FISH) and measurement of plasma follicle stimulating hormone (FSH) by radioimmunoassay. To determine Y chromosome microdeletions, polymerase chain reaction (PCR) of 16 sequence tagged sites (STS) and three genes (DFFRY, XKRY and RBM1 Y) was performed on isolated genomic DNA. Testicular fine needle aspiration cytology (FNAC) was done in selected cases. Results: Y chromosome microdeletions spanning the azoospermia factor (AZF)a and AZFb loci were found in four of the 14 azoospermic patients with KFS. Karyotype and FISH analysis revealed that, of the four cases showing Y chromosome microdeletion, three cases had a 47,XXY/46,XY chromosomal pattern and one case had a 46,XY/47,XXY/48,XXXY/48,XXYY chromosomal pattern. The testicular FNAC of one sample with Y chromosome microdeletion revealed Sertoli cell-only type of morphology. However, no Y chromosome microdeletions were observed in any of the 13 fertile men. All patients with KFS had elevated plasma FSH levels. Conclusion: Patients with KFS may harbor Y chromosome microdeletions and screening for these should be a part of their diagnostic work-up, particularly in those considering assisted reproductive techniques. (Asian JAndrol 2006 Jan; 8: 81-88)展开更多
According to the latest data,globally 15%of couples have infertility and male infertility contributes to 10%of all cases.Infertility can be caused by certain biological changes in the gonads and the reproductive syste...According to the latest data,globally 15%of couples have infertility and male infertility contributes to 10%of all cases.Infertility can be caused by certain biological changes in the gonads and the reproductive system like azoospermia,oligospermia,asthenospermia,teratozoospermia and hypospermatogenesis.Genetic causes of azoospermia include chromosomal abnormalities,Y chromosome microdeletions and deletion or other mutations of Y-linked genes.The maximum number of the genes are located in the azoospermia factor region of the long arm(Yq)of the Y chromosome.Y chromosome microdeletion is known as the second major genetic cause of spermatogenetic failure.This article aims to review the latest updates on the involvement of Yq microdeletions in male infertility.The diagnostics,prevalence and phenotypic spectrum related to Yq gene microdeletions are discussed.展开更多
The aim of the present work was to present the outcomes of the patients with Y-chromosome microdeletions treated by intracytoplasmic sperm injection (ICSI), either using fresh (TESE) or frozen-thawed (TESE-C) te...The aim of the present work was to present the outcomes of the patients with Y-chromosome microdeletions treated by intracytoplasmic sperm injection (ICSI), either using fresh (TESE) or frozen-thawed (TESE-C) testicular sperm and ejaculated sperm (EJAC). The originality of this work resides in the comparisons between the different types of Y-microdeletions (AZFa, AZFb, and AZFc) and treatments, with detailed demographic, stimulation, embryological, clinical, and newborn (NB) outcomes. Of 125 patients with Y-microdeletions, 33 patients presented severe oligozoospermia (18 performed ICSI with ejaculated sperm) and 92 secretory azoospermia (65 went for TESE with 40 having successful sperm retrieval and performed ICSI). There were 51 TESE treatment cycles and 43 TESE-C treatment cycles, with a birth of 19 NB (2 in AZFa/TESE-C, 12 in AZFc/TESE, and 5 in AZFc/TESE-C). Of the 29 EJAC cycles, there was a birth of 8 NB (in AZFc). In TESE and EJAC cycles, there were no significant differences in embryological and clinical parameters. In TESE-C cycles, there was a significant lower oocyte maturity rate, embryo cleavage rate and mean number of embryos transferred in AZFb, and a higher mean number of oocytes and lower fertilization rate in AZFc. In conclusion, although patients with AZFc microdeletions presented a high testicular sperm recovery rate and acceptable clinical outcomes, cases with AZFa and AZFb microdeletions presented a poor prognosis. Due to the reported heredity of microdeletions, patients should be informed about the infertile consequences on NB and the possibility of using preimplantation genetic diagnosis for female sex selection.展开更多
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)
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 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.
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 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Aim: To study the occurrence of Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome (KFS). Methods: Blood and semen samples were collected from azoospermic patients with KFS (n = 14) and a control group of men of proven fertility (n = 13). Semen analysis was done according to World Health Organization (WHO) guidelines. Blood samples were processed for karyotyping, fluorescent in situ hybridization (FISH) and measurement of plasma follicle stimulating hormone (FSH) by radioimmunoassay. To determine Y chromosome microdeletions, polymerase chain reaction (PCR) of 16 sequence tagged sites (STS) and three genes (DFFRY, XKRY and RBM1 Y) was performed on isolated genomic DNA. Testicular fine needle aspiration cytology (FNAC) was done in selected cases. Results: Y chromosome microdeletions spanning the azoospermia factor (AZF)a and AZFb loci were found in four of the 14 azoospermic patients with KFS. Karyotype and FISH analysis revealed that, of the four cases showing Y chromosome microdeletion, three cases had a 47,XXY/46,XY chromosomal pattern and one case had a 46,XY/47,XXY/48,XXXY/48,XXYY chromosomal pattern. The testicular FNAC of one sample with Y chromosome microdeletion revealed Sertoli cell-only type of morphology. However, no Y chromosome microdeletions were observed in any of the 13 fertile men. All patients with KFS had elevated plasma FSH levels. Conclusion: Patients with KFS may harbor Y chromosome microdeletions and screening for these should be a part of their diagnostic work-up, particularly in those considering assisted reproductive techniques. (Asian JAndrol 2006 Jan; 8: 81-88)
文摘According to the latest data,globally 15%of couples have infertility and male infertility contributes to 10%of all cases.Infertility can be caused by certain biological changes in the gonads and the reproductive system like azoospermia,oligospermia,asthenospermia,teratozoospermia and hypospermatogenesis.Genetic causes of azoospermia include chromosomal abnormalities,Y chromosome microdeletions and deletion or other mutations of Y-linked genes.The maximum number of the genes are located in the azoospermia factor region of the long arm(Yq)of the Y chromosome.Y chromosome microdeletion is known as the second major genetic cause of spermatogenetic failure.This article aims to review the latest updates on the involvement of Yq microdeletions in male infertility.The diagnostics,prevalence and phenotypic spectrum related to Yq gene microdeletions are discussed.
文摘The aim of the present work was to present the outcomes of the patients with Y-chromosome microdeletions treated by intracytoplasmic sperm injection (ICSI), either using fresh (TESE) or frozen-thawed (TESE-C) testicular sperm and ejaculated sperm (EJAC). The originality of this work resides in the comparisons between the different types of Y-microdeletions (AZFa, AZFb, and AZFc) and treatments, with detailed demographic, stimulation, embryological, clinical, and newborn (NB) outcomes. Of 125 patients with Y-microdeletions, 33 patients presented severe oligozoospermia (18 performed ICSI with ejaculated sperm) and 92 secretory azoospermia (65 went for TESE with 40 having successful sperm retrieval and performed ICSI). There were 51 TESE treatment cycles and 43 TESE-C treatment cycles, with a birth of 19 NB (2 in AZFa/TESE-C, 12 in AZFc/TESE, and 5 in AZFc/TESE-C). Of the 29 EJAC cycles, there was a birth of 8 NB (in AZFc). In TESE and EJAC cycles, there were no significant differences in embryological and clinical parameters. In TESE-C cycles, there was a significant lower oocyte maturity rate, embryo cleavage rate and mean number of embryos transferred in AZFb, and a higher mean number of oocytes and lower fertilization rate in AZFc. In conclusion, although patients with AZFc microdeletions presented a high testicular sperm recovery rate and acceptable clinical outcomes, cases with AZFa and AZFb microdeletions presented a poor prognosis. Due to the reported heredity of microdeletions, patients should be informed about the infertile consequences on NB and the possibility of using preimplantation genetic diagnosis for female sex selection.
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。