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Diagram of the human Y chromosome showing AZF deletions. A. Schematic representation of the structure of human Y chromosome showing pseudoautosomal region (PAR1, PAR2) , centromere and male-specific region of the Y chromosome (MSY) with eight palindromes (P1-P8), heterochromatic sequences and three classes of euchromatic sequences: X-transposed, X-degenerate and ampliconic. B. Schematic map of common AZF deletions with corresponding candidate genes. C. STS markers associated with AZFa, b and c regions respectively, used for routine screening analyses of Y chromosomal microdeletions globally (*; Multiple copy).
Source publication
Spermatogenesis is an essential stage in human male gamete development, which is regulated by many Y chromosome specific genes. Most of these genes are centred in a specific region located on the long arm of the human Y chromosome known as the azoospermia factor region (AZF). Deletion events are common in Y chromosome because of its peculiar struct...
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Citations
... Infertility is a complex reproductive problem due to the involvement of genetic and environmental factors in its development [17]. Genetic disturbances on the Y chromosome are known to have a critical role in the development of male infertility, especially the presence of microdeletions on the Y chromosome (Y chromosomal microdeletions/YCMs) [18][19][20]. YCMs are found in 10-15% of azoospermia patients and 5-10% of severe oligospermia patients. This genetic disorder usually occurs in the azoospermia factor (AZF) locus in the Yq11.23 band and is divided into three subregions: AZFa, AZFb, and AZFc [19,[21][22][23]. ...
... YCMs are found in 10-15% of azoospermia patients and 5-10% of severe oligospermia patients. This genetic disorder usually occurs in the azoospermia factor (AZF) locus in the Yq11.23 band and is divided into three subregions: AZFa, AZFb, and AZFc [19,[21][22][23]. ...
Y chromosome microdeletions (YCMs) are one kind of genetic disorder that contributes to male infertility. This study aims to determine the profile of YCMs in the infertile male population in Indonesia. This cross-sectional study was conducted by identifying YCMs testing data on 49 infertile male patients identified with azoospermia and oligoasthenoteratozoospermia (OAT) based on their sperm analysis, who visited andrology polyclinics in several hospitals in Yogyakarta Province between March 2021 to August 2022. Study participants underwent YCMs testing at the Molecular Medicine and Therapy Research Laboratory, Muhammadiyah University of Yogyakarta, Indonesia, using the Polymerase Chain Reaction (PCR) method according to the procedures established by the laboratory. Four out of 49 (8.2%) participants were identified to have YCMs with deletions in the Azoospermia Factor C (AZFc) subregion. Two participants identified with YCMs had cryptozoospermia in their sperm analysis. Hormonal examination showed variable results in 4 participants, including hypergonadotropic, hypogonadism, and normogonad. All participants in the study identified with YCMs showed a deletion in the AZFc subregion. This type of deletion is different from previous studies in Indonesia, so broad examinations of infertile male patients are required to figure out the deletion profile in a larger population of Indonesian sterile males.
... The most frequent deletion occurs in the AZFc region (~80%), followed by AZFb (1%-5%), AZFbc (1%-3%) and AZFa (0.5%-4%) 21 . Patients harboring deletion of AZFa can present hypo-spermatogenesis and inhibition of the production and maturation of germ cells 22,23 . The phenotype observed in patients with AZFb deletion is a pre-meiotic arrest with normal spermatogonia and primary spermatocytes. ...
... The DAZ2, CDY2, and PBY2 are the common deleted genes among our patients, and they are the same commonly reported genes deletion in the literature [35]. It was reported that these three genes are the important candidate genes in this area, and they are the key players in the process of the spermatogenesis [36,37]. ...
Background
The deletions of azoospermic factor regions (AZF) are considered risk factor of spermatogenic failure. AZF duplications or complex copy number variants (CNVs) were rarely studied because STS-PCR could not always detect these changes. The application of multiplex ligation-dependent probe amplification (MLPA) as a valuable test for detection of the deletion and or duplication was introduced to investigate the AZF sub-region CNVs. The MLPA technique is still not applied on a large scale, and the publications in this area of research are limited. The aim of this work was to evaluate the efficacy of MLPA assay to detect AZF-linked CNVs in idiopathic spermatogenic failure patients and to evaluate its importance as a prognostic marker in the reproduction outcome.
Results
Forty infertile men (37 with azoospermia and 3 with severe oligozoospermia) and 20 normal fertile men were subjected to thorough clinical, pathological, and laboratory assessment, chromosomal study, MLPA, STS-PCR assays, histopathology study, and testicular sperm retrieval (TESE). Out of the 40 patients, 7 patients have shown CNV in the AZFc region, 6 patients have partial deletion, and one patient has partial duplication. Only one of the normal control has AZFc duplication. STS-PCR was able to detect the deletion in only 4 out of the 7 positive patients and none of the control.
Conclusion
We concluded that MLPA should be applied on a larger scale for the detection of Y chromosome microdeletion as a rapid, efficient, and cheap test.
... The most frequent deletion occurs in the AZFc region (~80%), followed by AZFb (1%-5%), AZFbc (1%-3%) and AZFa (0.5%-4%) 21 . Patients harboring deletion of AZFa can present hypospermatogenesis and inhibition of the production and maturation of germ cells 22,23 . The phenotype observed in patients with AZFb deletion is a pre-meiotic arrest with normal spermatogonia and primary spermatocytes. ...
Aim:
Analysis of male infertility by molecular methods has increased since recognition of genetic risk factors. The AZFa, AZFb, AZFc, and gr/gr regions on the Y-chromosome can cause male infertility. The aim of this study was to determine the prevalence of Y-chromosome microdeletions in these regions in infertile Mexican patients.
Material and methods:
We recruited 57 infertile patients with abnormal sperm count (26 azoospermic and 31 oligozoospermic) and 55 individuals with normal sperm count. Analysis of the regions of interest was performed by PCR.
Results:
15.8% of infertile patients presented Y-chromosome microdeletions, whereas no deletions were found in the control group. Deletions were observed in all the analyzed regions except in AZFa. Additionally, the neural network model revealed a mild genotype-phenotype correlation between deletion of the sY1191, sY1291 and sY254 markers with oligozoospermia, azoospermia and cryptozoospermia, respectively.
Conclusions:
Our data show that AZFb, AZFc, and gr/gr microdeletions are significantly associated with infertility in Mexican population. In addition, the neural network model revealed a discrete genotype-phenotype correlation between specific deletions and a particular abnormality. Our results reinforce the importance of the analysis of AZF regions as part of the clinical approach of infertile men.
... Yq microdeletions are also second factor for infertility in the male. Deletions in azoospermia factor cause abnormal semen types such as azoospermia, oligozoospermia, and others [1,[10][11][12][13], leading to fertility anomalies. It has been reported that the chromosomal translocations which are structural anomalies reduce fertility in both men and women. ...
Introduction: Male infertility (MI) in about 50% of couples is constituted due to genetic, hormonal, and epigenetic factors. Almost 10% of it is contributed to genetic anomalies. Objectives: This study was undertaken in 787 males with infertility and the impacts of the type of translocations in these cases were studied in relation to MI. Materials and Methods: Five milliliters (ml) of blood were drawn from referred cases suspected with MI and were used for cytogenetic analysis with Giemsa stain following International System for Human Cytogenetic Nomenclature. Results: Of 6142 referral cases, 787 were detected with MI (787/6142; 12.8%). Forty-four translocations (44/787; 5.6%) were detected in 787 infertile men. Other chromosomal abnormalities were 21% (167/787) in them. Among all translocations, an autosome-autosomal translocations were higher in frequency (24/787; 3.1%) than Robertsonian (15/787; 1.9%) and autogonosomal translocations (5/787; 0.6%). Few translocations seemed to be rare as our knowledge is concerned. Maharashtra had high frequency of translocations followed by Delhi union territory (UT) and Gujarat (07 each) and other states. Most of the translocations were related to infertility. Seven males had primary infertility (7/44) and six with secondary type (6/44) in this study. Conclusions: These reciprocal translocations are important in causation of infertility affecting testicular spermatogenesis. Few are rare in our study. Such cases are clinically suggested for counseling before adopting assisted reproductive technologies.
... To date, 156 transcription unit coding genes and 27 different proteins encoded by Y chromosomes have been identified [53]. There are 7 deletion intervals in Y chromosomes in which region 5 and 6 are critical for spermatogenesis [54]. Euchromatic DNA is about 23 Mb long, the [17] Sickle cell Testicular ischemia and ultimately damage. ...
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.
... Male with reported impairment of spermatogenesis are frequently diagnosed as the cases of either azoospermia or oligozoospermia (Suganthi et al., 2013). Majority of these genes are located on the long arm of the human Y chromosome in a specific region termed as the azoospermia factor region (AZF; Suganthi et al., 2014). Molecular characterization and genetic dissection of Yq11.23 have identified three distinct, nonoverlapping subregions termed as AZFa, AZFb, and AZFc, each carrying candidate genes implicated in spermatogenesis and/or sperm maturation (Vogt et al., 1996). ...
... Since the last two decades, incidences of YCMD in the Indian populations have been reported in several studies. It is stated that the variation in the frequency of these micro-deletions is mostly because of differences in the study protocol and ethnic background (Suganthi et al., 2014). A meta-analysis study based on the YCMD frequency in the Indian population revealed the presence of AZF deletions in 10.02% of azoospermic and oligozoospermic men with the maximum frequency of AZFc deletions. ...
Background
Etiology of male infertility is intriguing and Y chromosome microdeletion within azoospermia factor (AZF) sub-regions is considered major cause. We conducted a screening for Y chromosome microdeletion in an infertile male cohort from West Bengal, India to characterize Y chromosome microdeletion among infertile men.
Methods
We recruited case subjects that were categorized on the basis of sperm count as azoospermia (N = 63), severe oligozoospermia (N = 38), and oligozoospermia (N = 17) and compared them with age, demography, and ethnicity matched healthy proven fertile control males (N = 84). Sequence Tagged Site makers and polymerase chain reaction based profiling of Y chromosome was done for AZF region and SRY for cases and controls.
Results
We scored 16.1% of cases (19 out of 118) that bear one or more microdeletions in the studied loci and none among the controls. The aberrations were more frequent among azoospermic males (17 of 19) than in severe oligozoospermic subjects (2 of 19).
Conclusion
Our study provides the results of screening of the largest Bengali infertile men sample genotyped with the maximum number of STS markers spanning the entire length of Y chromosome long arm. Y chromosome microdeletion is a significant genetic etiology of infertility among Bengali men.
... Although all our patients had breakpoints at Yq11.2, suspected by the karyotype and confirmed by the absence of Yq12 heterochromatin and the presence of 2 visibly separated centromers, a better characterization of these breakpoints would have been ideal, however, this was not possible for this study. The clinical consequences associated with this finding could be infertility secondary to: (1) spermatogenic failure due to loss of the distal Yq genes [cluster of genes of the azoospermia factor (AZF)], as these genes play critical roles in spermatogenesis [Kuroda-Kawaguchi et al., 2001;Lange et al., 2009;Suganthi et al, 2014]; (2) non-progression of meiosis due to disruption of meiotic pairing of chrX and chrY, because the presence of 2 copies of the short arm of chrY in an idic(Y)(q11.2) may result in duplication of the pseudoautosomal region of Yp (PAR1) and elimination of the pseudoautosomal region of Yq (PAR2) [Burgoyne and Baker, 1984;Mohandas et al., 1992]; and (3) spermatogenic defects because of the chrX mosaicism resulting from germline instability of idic(Y) [Guedes et al., 2006;Lehmann et al., 2012]. Sexual reversal and Turner syndrome are other consequences of the mitotic instability of the idic(Y) during embryonic and fetal development. ...
Isodicentric Y chromosome [idic(Y)] is one of the most common structural abnormalities of the Y chromosome and has been observed in patients with reproductive disorders and in patients with disorders of sexual development. Most idic(Y) chromosomes are found in mosaic form with a 45,X cell line. These chromosomes are highly unstable during mitosis due to the presence of 2 centromers, which explains their probable loss in early mitosis or mitosis of the embryo and therefore the presence of the 45,X line. It has been hypothesized that the proportion of 45,X cells in various tissues probably influences the phenotypic sex of individuals carrying an idic(Y) chromosome, ranging from infertile men, hypospadias, ambiguous genitalia, and Turner syndrome to sex reversal. In this article we present 5 cases of patients with idic(Y) referred for suspected disorder of sex development (DSD), 3 with a male assignment and 2 with a female assignment. All cases have variable clinical characteristics, which were assessed by the transdisciplinary group of Disorders of Sex Development of the Hospital Universitario San Ignacio, Bogotá, Colombia. Patients were analyzed by conventional and molecular cytogenetics using high-resolution G-band and FISH techniques. Our findings highlight the importance of cytogenetic studies in the diagnosis of DSD patients.
... Only complete deletion of AZFa region is associated with sertoli cell only syndrome (SCOS). In cases of deletion of AZFa, sperm retrieval is still possible in partial deletion of AZFa [13,19]. ART should be offered to those couples with AZFc deletion with own partner semen. ...
Background: In the work up of male infertility, Y chromosome microdeletion screening is crucial. PCR is a very sensitive technique to screen Y chromosome microdeletion. In the current study, Y chromosome microdeletion was detected by PCR based technique. To the best of our knowledge, no such study has been reported from Chhattishgarh state of India so far. Material and methods: A total of seventy-three subjects were enrolled for the study during the period of one year. Out of which forty-seven subjects were cases (infertile men with oligozoospermia and azoospermia) and twenty-five were controls (with normozoospermia and having child). Semen analysis was done in each case to evaluate spermatogenesis status. Sperm DNA fragmentation by sperm chromatin dispersion of cases with oligozoopermia was also performed to detect DNA fragmentation Index. Results: Y chromosome microdeletion was observed in one out of forty-seven infertile males who were oligozoospermic or azoospermic. The type of deletion was AZFbc. Thus 2.12% men among oligozoospermic or azoospermic men have Y chromosome microdeletion in Chhattisgarh. Conclusion: In Indian population, AZFbc deletion has been found to be the second commonest type of deletion. In our study, we have also found this as the only deletion. This test also provides etiological interpretation of male infertility to the patient. We believe that awareness about transmission of deleted gene to the offspring could prevent infertility up to certain extent in the affected couples.
... In the last two decades, various studies have reported high frequency of Y chromosome microdeletion in Indian infertile male population (Suganthi et al. 2014;Sen et al. 2013;Khan et al. 2010;Agarwal et al. 2015;Ambulkar et al. 2015). However, the observed frequency is variable in different studies which may be due to variable sample size or additional genetic and environmental factors. ...
... In accordance with the previous studies (Ambulkar et al. 2015), we found AZFc region as most susceptible for deletion and is observed in 84% of cases. Microdeletion in AZFc region is the most common deletion type both in Indian and European populations and is found in more than 70% of the cases (Foresta et al. 2001;Thangaraj et al. 2003) The AZFc locus contains 21 candidate genes and 11 families of transcription units specifically expressed in testis (Suganthi et al. 2014). The most important and well-studied AZFc gene is DAZ. ...
Deletion of specific genes present in the long arm of Y chromosome has been identified as the most common genetic cause of defective spermatogenesis. Studies have shown that frequency of Y chromosome microdeletion varies in different geographical location and is related to genetic and environmental influence preponderance. Therefore, the present study was carried out to identify the frequency of Y chromosome microdeletion in the northern region of India and to define subgroup of infertile patients who are critically under more risk of having microdeletion. A total of 292 north Indian infertile males with nonobstructive azoospermia and oligozoospermia were selected for screening the Y chromosome microdeletion. Healthy fertile males (n=100) were also enrolled as control subjects. Frequency of Y chromosome microdeletion in north Indian infertile males was found to be about 8.5%, with azoospermia factor (AZFc) region as the most susceptible region for microdeletion. Comparatively microdeletion is more common in patients with nonobstructive azoospermia than oligozoospermia (9.2% versus 7.1%). Statistical analysis also revealed that patients with hormonal FSH level between 20 and 40 mIU/mL have more chances of harbouring microdeletion. Hence, the present study highlights the importance of screening AZFc region among infertile patients with very high serum FSH value.
