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Schematic diagram of Y-chromosome showing AZF loci and their candidate gene associated with infertile male patients.
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Infertility is a major reproductive health threat; the frequency of male infertility due to Y-chromosome microdeletions is 13-18% in the human population; these microdeletions involve recurrent loss of three non-overlapping regions designated as AZFa, AZFb and AZFc, associated with spermatogenic failure. Several contradictory reports have been publ...
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... incidence of Y-chromosome microdeletion varies from 1 (van der Ven et al., 1997) to 50% ( Foresta et al., 1998) in idiopathic and non-idiopathic azoospermic or severe oligoazoospermic patients ( Henegariu et al., 1994;Vogt et al., 1996). Recent studies on infertility-controlling spermatogenesis in men are involving azoospermic factors (AZFc), present in the long arm of the Y-chromosome (Figure 1). Study of Yq microdeletion is quite relevant to the understanding of the mechanism of spermatogenesis, because the individuals are of different genetic background ( Ma et al., 1993). ...
Similar publications
The Y chromosome accumulates male-related genes including sex-determining region of Y-chromosome (SRY) and several spermatogenesis-related genes. The long arm contains azoospermia factor (AZF) region (including sub-regions AZFa, AZFb and AZFc). Microdeletions in this region are responsible for azoospermia and oligospermia and result in the male inf...
In addition to Klinefelter's syndrome, microdeletion of Yq is the most common genetic cause of male infertility; 15% of azoospermic or 5-10% of oligozoospermic males have Yq deletions. We evaluated a Yq microdeletion kit (LG Life Sciences, Korea) for identifying microdeletions in the azoospermic factor (AZF) regions of the Yq.
The kit was designed...
AIM:
The aim of this study was to analyze human seminal plasma proteins in association with male fertility status using the proteomic mass spectrometry technology Surface-Enhanced Laser Desorption Ionization Time-of-Flight (SELDI-TOF-MS).
MATERIALS AND METHODS:
Semen analysis was performed using conventional methods. Protein profiles of the semina...
Citations
... Published data earlier showed that the frequency of microdeletions in the Indian population ranged from 3% to 29.34% with an average frequency of 8.1% [9,19,32,64,65]. Thangaraj et al. [66] proposed 8.5% Y chromosome microdeletion from the study of 340 azoospermia infertile cases. ...
... The same group had also mentioned low frequency 5.8% deletions [4], but our study cohort exhibited 8.33% deletions from 5435 Y chromosomes analyzed supporting the data of Thangaraj et al. [54], Pandey et al. [65], and Dada et al. [32]. Recently Rozen et al. [10] also reported similar data falling in the range of 8-10%. ...
... Tiepoli and Zuffardi (1976), that the mutation of 5.3% frequency of AZFc region where as in the present study reveals statistically significant frequency (19%) of the same locus which was more than three times higher in Eastern part of India. Although, there is a variation in the frequency of microdeletion of AZFc region showing variation of 3% -3.5% between South Indian and Eastern Indian populations, respectively 2003; Pandey et al., 2010). Similar findings has also been reported by Kerr et al., 2000, in the frequency of microdeletion upto 20% in Swedish population and New Zeland population. ...
Introduction: Male infertility is a serious problem in developing world where genetic and epigenetic factors play a crucial role in the pathogenesis of the disease. The rationale behind the present study to understand the genetic basis of male infertility, to identify the “novel gene mutation” and also asses the frequency (%) of microdeletion of Y-chromosome i.e. deletion of AZF regions interfare during spermatogenesis. Still, 10-20% cases of infertility fail to identify exact cause of male infertility and are fall in the category of unexplained cause of infertility in non obstructive azoospermia. Material and Methods: Blood samples were collected from the cases of clinically diagnosed non obstructive azoospermia (NOA) with respective controls. Study was performed using RT-PCR based analysis using 14 set of STS markers of AZF region allocated on Y- chromosome and NextGen Sequencing. Results: Mutational spectra include the individual variations of frequency of AZF gene mutation as a factor responsible for male infertility in eastern part of the country. Genetics analysis of AZF a, b, and c regions showing different frequency of deletion but the deletion of AZFc showing significant difference with respect to controls (p<0.001). NGS play a significant role to explore the involvement of de novo mutation of USP9Y and PCDH11Y gene mutation resulting changes in protamines. The deletion frequency AZFa region is 1.0%, while AZFb and AZFc regions showing 6% & 19%, respectively in non obstetric azoospermic cases. Hence, curiosity has been developed further to identify “new mutations” based on Next Gen Sequencing, identifies USP9Y gene of AZFa region showing non-frame shift mutation (insertion of C→G/C→A) at region exon42:c.6996_6997 insCGA in heterozygous condition. Secondly, of AZFb region showing single nucleotide gene polymorphism rs2524543, G→T and rs2563389, T→ G of PCDH11Y gene in homozygous condition. Conclusion: The identification of causative mutations in the cases of NOA and their penetrance lead to interference in spermiogenesis .Hence, on the basis of mutational spectra, genetic counselling of infertile couples are required before reaching to final decision. No doubt the environmental factors influence the gene-pool lead to altered spermatogenesis in male infertility.
... [31] In azoospermic cases, the presence of a complete and the absence of AZFa or AZFb regions have a negative prognostic value for testicular sperm retrieval. [32][33][34][35][36] ...
... AZF can be further subdivided into 3 regions, including AZFa, AZFb, and AZFc. Each region contains several candidate genes involved in different stages of spermiogenesis, and deletions or mutations in these genes may cause spermatogenesis disorder, resulting in oligozoospermia or azoospermia (Pandey et al., 2010). In addition, some scholars identified a region known as AZFd between AZFb and AZFc (Kent-First et al., 1999). ...
... Although DAZ is not absolutely necessary for sperm formation, but the absence of DAZ is observed in approximately 10-15% of azoospermia patients and is the most frequent genetic factor in male infertility. In general, a proportion of patients with deletions of the AZFc region may still have sperm in the ejaculate and sperm within the testis on diagnostic biopsy or upon testicular sperm extraction; very few cases have shown that deletions of AZFc can be inherited (Pandey et al., 2010). ...
We investigated azoospermia region microdeletions in male infertility patients with Klinefelter syndrome (KFS), as well as the association between azoospermia symptoms in patients with KFS and Y chromosome microdeletion polymorphisms. A total of 111 cases with male infertility confirmed to have KFS (47, XXY) and 94 fertile men were included in this study. Peripheral blood was drawn and DNA was extracted from these samples. Multiplex polymerase chain reaction was performed to screen the partial deletions of 25 sequence-tagged sites on the Y chromosome. In 111 cases with KFS, 1 case contained the AZFb+d+c deletion. The Gr/Gr deletion was identified in 12 KFS cases and 5 control cases. In addition, the b2/b3 deletion was identified in 13 KFS cases and 6 control cases. There were no significant differences in phenotype and genotype of the 2 partial AZFc deletions between patients and controls (P > 0.05). Our results suggest that patients with KFS may also have Y chromosome microdeletions to varying degrees and that the gr/gr deletion and b2/b3 deletion may not play a role in the susceptible genetic background of azoospermia in patients with KFS in the Sichuan population.
... Within the Yq11 region, AZF can be divided into three non-overlapping subregions: AZFa, AZFb and AZFc, which have been known to be associated with sertoli cell only syndrome (SCOS), spermatogenic maturation arrest at meiosis, and diverse phenotype (including hypospermatogenesis, severe oligozoospermia, azoospermia, or even SCOS) (Liu et al., 2013;Kihaile et al., 2004;van Golde et al., 2001;Zhang et al., 2014), respectively. The incidence of the Y chromosome microdeletion is about 7% among the infertile men, within a range of 3-55% according to previous studies (Pandey et al., 2010;Dai et al., 2012). The discrepancies of the findings in these studies mainly result from differences in the criteria and sample size of patients recruited and the number of sequence tagged site (STS) markers selected. ...
... However, Pandey et al. [24] show that hormonal levels (FSH, LH and testosterone) showed significantly higher (P <0.001) in relation to controls, when evaluated 64 men with infertility, of which 3% were in AZFc microdeletion. São Pedro et. ...
... In Pandey et. al. [24] there was the frequency of 3% of the AZFc microdeletion region, and no mutations were observed in AZFa and AZFb regions, maybe due to selective use of sequences of markers. ...
... Its etiopathogenesis is not well understood, however, it's known the importance of the role of microdeletion of subregions of the Ychromosome in the casuistry. The literature indicates that deletion of AZF, especially AZFc [12,19,32], is related to azoospermia [1,5,10,18,21,26,31,35], oligozoospermia [10,18,21,31,36] , infertility [4,24] or even normal fertility [7]. The absence of other loci is also underlined by the evidence: AZFa, AZFb, AZFd [10,20,21,23,25,29] and although the prevalence rates are not equidistant. ...
Objective: evaluate the current evidence regarding different aspects (Epidemiological, histological, physiological and genetic) of male infertility caused by Y-chromosome microdeletion.
Material and Methods: A systematic review of articles from January 1st, 1996 and February 28th, 2014 present in two databases: MEDLINE and SciELO. The search was performed with the MeSH descriptors "Y Chromosome", "Infertility” and Keyword "microdeletion".
Results: The literature indicates that deletion of AZF, especially AZFc, is related to azoospermia, oligozoospermia or even infertility. The absence of other loci is also underlined by the evidence: AZFa, AZFb and AZFd, even though the prevalence rates are not equidistant. Surveys also show changes in the male hormone physiology varying the levels of testosterone/LH/FSH as well as modifying the gonadal morphology in individuals affected by Y-chromosome microdeletion.
Conclusion: More research is needed focusing on possible deletions that the Y-chromosome may suffer, giving emphasis on their clinical outcomes and correlations with infertility.
... with a range of 3-55% according to previous studies (Pandey et al., 2010;Dai et al., 2012). Generally, the azoospermia factor (AZF) on Yq11 region can be subdivided into three regions: AZFa, AZFb and AZFc, which have been proposed to be associated with Sertoli cell only syndrome (SCOS), spermatogenic maturation arrest at meiosis, and hypospermatogenesis (including mild oligozoospermia, severe oligozoospermia or azoospermia), respectively (Liu et al., 2013;Kihaile et al., 2004;van Golde et al., 2001). ...
Summary This study aimed to explore whether the presence of a Y chromosome azoospermia factor (AZF) microdeletion confers any adverse effect on embryonic development and clinical outcomes after intracytoplasmic sperm injection (ICSI) treatment. Fifty-seven patients with AZF microdeletion were included in the present study and 114 oligozoospermia and azoospermia patients without AZF microdeletion were recruited as controls. Both AZF and control groups were further divided into subgroups based upon the methods of semen collection: the AZF-testicular sperm extraction subgroup (AZF-TESE, n = 14), the AZF-ejaculation subgroup (AZF-EJA, n = 43), the control-TESE subgroup (n = 28) and the control-EJA subgroup (n = 86). Clinical data were analyzed in the two groups and four subgroups respectively. A retrospective case-control study was performed. A significantly lower fertilization rate (69.27 versus 75.70%, P = 0.000) and cleavage rate (89.55 versus 94.39%, P = 0.000) was found in AZF group compared with the control group. Furthermore, in AZF-TESE subgroup, the fertilization rate (67.54 versus 74.25%, P = 0.037) and cleavage rate (88.96 versus 94.79%, P = 0.022) were significantly lower than in the control-TESE subgroup; similarly, the fertilization rate (69.85 versus 75.85%, P = 0.004) and cleavage rate (89.36 versus 94.26%, P = 0.002) in AZF-EJA subgroup were significantly lower than in the control-EJA subgroup; however, the fertilization rate and cleavage rate in AZF-TESE (control-TESE) subgroup was similar to that in the AZF-EJA (control-EJA) subgroup. The other clinical outcomes were comparable between four subgroups (P > 0.05). Therefore, sperm from patients with AZF microdeletion, obtained either by ejaculation or TESE, may have lower fertilization and cleavage rates, but seem to have comparable clinical outcomes to those from patients without AZF microdeletion.
... About 15-20% of married couples belongs to sub-or infertile category and a small fraction of these couples opt for ART in India (86). In the last two decades, several studies have reported the incidence of Y chromosomal microdeletions in the Indian population (Table 2) and emphasised on the need for the molecular diagnosis of deletions in the workup of male infertility (87)(88)(89)(90)(91)(92). Even though a large number of infertility clinics are present in India, half of them still rely on classic cytogenetic analysis to find out genetic defects. ...
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 structural organization. Astonishingly, among the several known genetic causes of male infertility, Y chromosomal microdeletions emerged as the most frequent structural chromosome anomaly associated with the quantitative reduction of sperm. The development of assisted reproductive techniques (ART) like intra-cytoplasmic sperm injection (ICSI) and testicular sperm extraction (TESE) helps to bypass the natural barriers of fertilization, but it increases the concern about the transmission of genetic defects. Experimental evidence suggested that the men with Y chromosomal microdeletions vertically transmitted their deletion as well as related fertility disorders to their offspring via these ART techniques. In India, infertility is on alarming rise. ART centres have opened up in virtually every state but still most of the infertility centres in India do not choose to perform Y chromosomal microdeletion diagnosis because of some advanced theoretical reasons. Moreover, there is no consensus among the clinicians about the diagnosis and management of Y chromosomal microdeletion defects. The current review discusses thoroughly the role of Y chromosome microdeletion screening in the workup of male infertility, its significance as a diagnostic test, novel approaches for screening Y deletions and finally a systematic review on the current status of Y chromosome microdeletion deletion screening in India.
... In mammals, deletions and translocation of Y-linked genes cause sterility and many of these genes are known to be involved in sperm production and function [62][63][64]. There are several other notable additions to the DmSP-II including 4 Ylinked genes, kl-3, kl-5, ARY and ORY. ...
Advances in mass spectrometry technology, high-throughput proteomics and genome annotations have resulted in significant increases in our molecular understanding of sperm composition. Using improved separation and detection methods and an updated genome annotation, a re-analysis of the Drosophila melanogaster sperm proteome (DmSP) has resulted in the identification of 956 sperm proteins. Comparative analysis with our previous proteomic dataset revealed 766 new proteins and an updated sperm proteome containing a total of 1108 proteins, termed the DmSP-II. This expanded dataset includes additional proteins with predicted sperm functions and confirms previous findings concerning the genomic organization of sperm loci. Bioinformatic and protein network analyses demonstrated high quality and reproducibility of proteome coverage across three replicate mass spectrometry runs. The use of whole-cell proteomics in conjunction with characterized phenotypes, functional annotations and pathway information has advanced our systems level understanding of sperm proteome functional networks.
Background: Infertility has been a significantly growing problem worldwide, affecting approximately 10-15% of couples within reproductive age. Among the many causes of male infertility, Y-chromosome microdeletion is considered one of the most frequent genetic causes. Thus, this systematic review was constructed to determine the prevalence of Y-chromosome microdeletion and the population variations in the different types of Y-chromosome microdeletions.
Methods: We searched the PubMed, Scielo, and Science Direct databases to obtain articles that addressed the frequency of Y-chromosome microdeletion and male infertility. We identified 14 articles that originated from China, India, Iran, Brazil, Indonesia, North America, South Korea, and Slovakia, and the vital information collected included the year of publication, authors, number of patients with different types of Y-chromosome microdeletions, and the proportion of microdeletion in the major affected sub-regions of the Y-chromosome.
Results: In this review, we attempted to highlight the variation in the frequency of Y-chromosome microdeletion in different geographical populations. The highest and lowest frequencies of Y-chromosome microdeletion were found in Indonesian (23.94%) and Slovakian (3.5%) populations, respectively.
Conclusion: In conclusion, Y-chromosome microdeletion was undeniably found to be one of the leading genetic causes of male infertility. Azoospermic factor c (AZFc) microdeletion was the most frequent type of Y-chromosome microdeletion, typically presenting in patients with various clinical manifestations that ranged from oligozoospermia to azoospermia and exhibiting the highest chance for sperm retrieval. This review will undoubtedly help clinicians in providing a more accurate consultation to their patients and determining the success rates of assisted reproductive technology.
