Figure 1 - uploaded by Rima Dada
Content may be subject to copyright.
Schematic representation of the Y chromosome showing seven deletion intervals and pseudoautosomal region (PAR) 1 and 2.
Source publication
Infertility affects 15% couples attempting pregnancy and in 40-50% of these cases the male partner has qualitative or quantitative abnormalities of sperm production. Microdeletions in the azoospermia factor (AZF) region on the long arm of the Y chromosome are known to be associated with spermatogenic failure and have been used to define three regio...
Context in source publication
Similar publications
Defined infertility as incapability of a married couple tᴏ have children for the one-year ᴏf unprotected intercourse. Y chromosomal microdeletions are the second greatest common genetic reason of men sterility. This research aims to find the prevalence of AZF Y chromosome microdeletions in azoospermic and severe oligospermia patients. Further, to e...
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...
To apply capillary electrophoresis for rapid screening for Y microdeletions
A set of 25 specific sequence tagged sites that cover the azoospermia factor a, b, and c regions of the Y chromosome was amplified in 5 fluorescent multiplex sets each including 5 primer pairs. One of the primers of each pair was labeled with a fluorescent tag attached to t...
Cytogenetic investigations and molecular analysis of the Y chromosome by the polymerase chain reaction amplification of sequence-tagged sites (STS-PCR) technique were performed in 126 patients affected by idiopathic oligo-azoospermia following accurate selection of cases. Seventeen patients evidenced an abnormal karyotype. Fourteen patients with a...
Chromosomal abnormalities and Y chromosome microdeletions are considered to be the two more common genetic causes of spermatogenic failure. However, the relationship between chromosomal aberrations and Y chromosome microdeletions is still unclear. This study was to investigate the incidence and characteristics of chromosomal aberrations and Y chrom...
Citations
... According to the latest report of the World Health Organization, the prevalence of infertility among couples of childbearing age in the world ranges from 12.6% to 17.5%, affecting approximately one-sixth of the global population [1]. Among them, male infertility accounts for 50% [2]. Among male infertility factors, spermatogenesis disorder is the most common, with clinical manifestations of azoospermia and oligoasthenospermia. ...
The long arm of the Y chromosome (Yq) contains many amplified and palindromic sequences that are prone to self-reorganization during spermatogenesis, and tiny submicroscopic segmental deletions in the proximal Yq are called Y chromosome microdeletions (YCM). A retrospective study was conducted on male infertility patients of Zhuang ethnicity who presented at Reproductive Medical Center of Nanning between January 2015 and May 2023. Seminal fluid was collected for standard examination. YCM were detected by using a combination of multiplex PCR and agarose gel electrophoresis. Preparation of peripheral blood chromosomes and karyotyping of chromosomes was performed. 147 cases (9.22%) of YCM were detected in 1596 male infertility patients of Zhuang ethnicity. Significant difference was found in the detection rate of YCM between the azoospermia group and the oligospermia group ( P < 0.001). Of all types of YCM, the highest detection rate was AZFc ( n = 83), followed by AZFb + c ( n = 28). 264 cases (16.54%) of sex chromosomal aberrations were detected. The most prevalent karyotype was 47, XXY ( n = 202). The detection rate of sex chromosomal aberrations in azoospermia group was higher than that in severe oligospermia group and oligospermia group, and the differences were significant ( P < 0.001). 28 cases (1.57%) of autosomal aberrations and 105 cases (6.58%) of chromosomal polymorphism were identified. The current research has some limitations due to the lack of normal men as the control group but suggests that YCM and chromosomal aberrations represent key genetic factors influencing spermatogenesis in infertile males of Zhuang ethnicity in Guangxi.
... 21 With deletions in the AZFb region, many large hospitals worldwide have employed the sY127 and sY134 sequences to confirm the diagnosis. [22][23][24][25][26][27][28][29][30] Similar to deletions in the AZFa region, according to the recommendations of EAA/ EMQN, the complete loss of sY127, sY134 of AZFb require further identification of additional extended microdeletions: sY105 and sY121 or sY1224 for the proximal border and sY143 or sY1192 and sY153 for the distal border. 21 Regarding deletions in the AZFc region, sY54 and sY255 are recommended by EAA/EMQN as representatives of the AZFc region. ...
Background
To optimize the multiplex polymerase chain reaction (M-PCR) technique to diagnose microdeletions of azoospermia factors (AZF) on the Y chromosome and initially apply the technique to diagnose male patients with sperm density less than 5×10⁶ million sperm/mL was assigned to do a test to check for AZF microdeletions on the Y chromosome.
Methods
Based on the positive control samples which belong to male subjects who have had 2 healthy children without any assisted reproductive technologies, the M-PCR method was developed to detect simultaneously and accurately AZF microdeletions on 32 male patients with sperm densities below 5×10⁶ million sperm/mL of semen at the Department of Biology and Medical Genetics – Vietnam Military Medical University.
Results
Successful optimization of the M-PCR technique including 7 reactions arranged according to each AZFabc region using 24 STS/gene on the Y chromosome. Initial application to diagnose AZF deletion on 32 azoospermic and oligospermic men reveals that AZFa deletion accounts for 6.25% (2/32); deletion of all 3 regions AZFa,b,c with 18.75% (6/32 cases); The combined deletion rate of AZFb,c is highest, accounting for 56.24% (18/32 patients).
Conclusion
Successfully optimized the M-PCR technique in identifying AZF microdeletions using 24 sequence tagged sites (STS)/gene for azoospermic and oligozoospermic men. The M-PCR technique has great potential in the application of AZF deletion diagnosis.
... [24] There are signi cant racial and regional differences in the probability and type of AZF microdeletions, with an incidence rate of 8-18% in Europe and 6.7-13% in Asia. [25,26] AZFc deletion is mainly the type of Y chromosome deletion in all regions, and the AZFc microdeletion rate in some regions exceeds 80%. [3,24] The non-allelic homologous recombination mediated by the amplicon of the MSY sequence is the direct cause of AZF microdeletion, but external environmental factors can also indirectly cause microdeletion. ...
Backgroud: Y chromosome microdeletions is an important cause of male infertility. At present, research on the Y chromosome mainly focuses on analyzing the loss of large segments of the AZFabc gene, and few people have studied the impact of unit point deletion in the AZF band on fertility.
Methods: A total of 15 associated sequence tag site loci in the AZF region of the Y chromosome in 2,000 patients with oligoasthenospermia were tested, and 116 patients with AZF microdeletion were selected. Calculated the proportion of azoospermia caused by the sY1192 deletion. The proportion and type of sY1192 independent and combined deletions in the AZFb/c region were determined to analyze the changes in the associated sex hormone levels due to the loss of sY1192 and the pregnancy outcomes of patients with weak or obstructive assisted reproductive techniques to assist in pregnancy.
Results: Among the 116 patients with AZF microdeletion, the sY1192-independent deletion accounted for 41.38% (48/116), and the sY1192 combined deletion with other loci accounted for 25.86% (30/116). Eight patterns were found in the deletions associated with sY1192: the independent deletion of sY1192 (61.5%, 48/78); the common deletion of sY1192 and sY153 (1.3%, 1/78); the common deletion of sY1192, sY153, sY254, and sY255 (26.9%, 21/78); the common deletion of sY1192, sY121, sY127, and sY134 (1.3%, 1/78); the common deletion of sY1192, sY121, sY127, sY134, sY153, sY254, and sY255 (1.3%, 1/78); the common deletion of sY1192, sY121, sY127, sY134, sY153, sY254, sY255, and sY160 (3.8%, 3/78); the common deletion of sY1192, sY105, sY121, sY134, sY152, sY153, sY254, sY255, and sY160 (1.3%, 1/78); and 15 missing loci (2.6%, 2/78). The sperm detection rate was similar in the semen of patients with sY1192 independent deletion and sY1192 combined deletion (52.1% vs. 50.0%, P > 0.05). The sperm detection rate was higher than that in other types of microdeletions present at the sY1192 locus (52.1% vs. 32.0%, P < 0.05). The hormone levels were similar in patients with sY1192 deletion alone and in those with sY1192 deletion and other types of microdeletions in the presence of the sY1192 locus (P > 0.05), but the Follicle stimulating hormone (FSH), Luteinizing hormone (LH), Estradiol (E2),andTestosterone (T) were higher than those in the normal human controls (P < 0.05). After multiple intracytoplasmic sperm injection (ICSI) techniques, the total pregnancy rate of sY1192 independent deletion was similar to that of other types of microdeletions (73.9% vs. 75.0%, P > 0.05), but the fertilization rate and cleavage rate were higher (P < 0.05).
Conclusions: Eight deletion patterns were observed for sY1192 microdeletions of AZFb/c, dominated by the independent deletion of sY1192. Combined deletions mostly occurred in sY1192, sY153, sY254, and sY255 (the b2–b4 amplicon region distributed in the AZFc region). The FSH, T, E2, and LH levels in patients with sY1192 deletions were higher than those in normal subjects and were not different from other types of microdeletions. After ICSI, the fertilization rate and cleavage rate of the sY1192 independent microdeletion were higher than those of other Y chromosome microdeletion types, but there was no difference in pregnancy outcomes.
... With the increase of life pressure, infertility is increasing every year. About 15% of gestational age couples suffer from infertility symptoms of varying degrees, of which about 50% are caused by male infertility (Dada et al., 2003). About 7% of men in the general population suffer from different degrees of infertility. ...
Male infertility has always been one of the important factors affecting the infertility of couples of gestational age. The reasons that affect male infertility includes living habits, hereditary factors, etc. Identifying the genetic causes of male infertility can help us understand the biology of male infertility, as well as the diagnosis of genetic testing and the determination of clinical treatment options. While current research has made significant progress in the genes that cause sperm defects in men, genetic studies of sperm content defects are still lacking. This article is based on a dataset of gene expression data on the X chromosome in patients with azoospermia, mild and severe oligospermia. Due to the difference in the degree of disease between patients and the possible difference in genetic causes, common classical clustering methods such as k-means, hierarchical clustering, etc. cannot effectively identify samples (realize simultaneous clustering of samples and features). In this paper, we use machine learning and various statistical methods such as hypergeometric distribution, Gibbs sampling, Fisher test, etc. and genes the interaction network for cluster analysis of gene expression data of male infertility patients has certain advantages compared with existing methods. The cluster results were identified by differential co-expression analysis of gene expression data in male infertility patients, and the model recognition clusters were analyzed by multiple gene enrichment methods, showing different degrees of enrichment in various enzyme activities, cancer, virus-related, ATP and ADP production, and other pathways. At the same time, as this paper is an unsupervised analysis of genetic factors of male infertility patients, we constructed a simulated data set, in which the clustering results have been determined, which can be used to measure the effect of discriminant model recognition. Through comparison, it finds that the proposed model has a better identification effect.
... Previous studies concerning Y chromosome microdeletion in the AZFc region showa discrete percentage of deletion among different parts of India. Broadly, in North India, on average, 46.5 percent (Dada et al. 2003;Mahanta et al. 2011;Thangaraj et al. 2003), likewise 45.34 percent of average in Central India (Ambulkar et al. 2015;Ambulkar et al. 2014) and closely 44.85 percent in South India (Papanna et al. 2015;Vijesh et al. 2015;Vineeth et al. 2015) have been reported. These results show that the AZFc region has a crucial role in the proper functioning of spermatogenesis, resulting in infertility, which is inheritable in upcoming generations. ...
This work aims to analyze Y-chromosome microdeletion in AZFc region of Oligoasthenoteratozoospermic (OAT) patients and oxidative damage profile in idiopathic OAT patients. Peripheral blood, serum, and semen samples of 57 OAT men and 57 fertile controls samples were collected for analyzing YCMD in the AZFc region using polymerase chain reaction and gel electrophoresis and to understand the oxidative damage level, total antioxidant capacity (T-AOC), Human 8-Hydroxy-deoxyguanosine (8-OHdG), Lipid peroxidation (LPO) and nitric oxide (NO) profiles were used. Out of the 57 OAT men, nine (15.7%) were observed with AZFc deletion. The remaining 48 idiopathic infertile men samples were analyzed for oxidative damage. The T-AOC levels were significantly reduced inpatient samples than in the control (p<0.05). This study shows that testing YCMD and oxidative stress damage analysis is necessary before undergoing Assisted Reproductive Technology (ART).
... Among them, only 14-15% have oligospermia, asthenospermia, or teratospermia. 3 Therefore, semen parameters may not accurately indicate male fertility. ...
Objective
The objective of this study is to reduce the dimension of several indicators with a strong correlation when conducting semen quality analysis in a small number of comprehensive variables that could retain most of the information in the original variables.
Methods
A total of 1132 subjects were recruited from the Maternal and Child Health Institutions of seven provinces in mainland China. They completed the questionnaire and provided semen samples. Visualization of the correlation between variables was realized by using a function chart and correlation in the PerformanceAnalytics package of the R programming language (version 3.6.3 [2020-02-29]). Factor analysis was conducted using the principal function in the psych package of R. Principal component analysis, combined with varimax rotation, was used in the operation of the model, and two common factors were selected and measured to provide values for the common factor. The score coefficient was estimated using the regression method.
Results
The contribution rates of the two common factors to variable X were 43.7% and 33.98%, respectively. When the two common factors were selected, approximately 78% of the information of the original variables could be explained. The correlation coefficients between the first common factor (the quantitative factor) and sperm density, total sperm count, and semen volume were 0.824, 0.984, and 0.544, respectively. The correlation coefficients between the second common factor (the quality factor) and sperm motility and the percentage of forward-moving (progressive spermatozoa) sperm were 0.978 and 0.976, respectively.
Conclusion
The correlation between the original variables of a semen quality analysis was strong and suitable for dimensionality reduction by factor analysis. Factor analysis and dimensionality reduction provide a fast and accurate assessment of semen quality. Patients with low fertility or infertility can be identified and provided with corresponding treatments.
... Currently, infertile couples account for about 15% of married couples worldwide, and male infertility accounts for 40-50% (Dada et al., 2003). The etiology of infertility is complex, and the detection methods and related research are still relatively sparse. ...
The World Health Organization predicts that infertility will be the third major health threat after cancer and cardiovascular disease, and will become a hot topic in medical research. Studies have shown that epigenetic changes are an important component of gametogenesis and related reproductive diseases. Epigenetic regulation of noncoding RNA (ncRNA) is appropriate and is a research hotspot in the biomedical field; these include long noncoding RNA (lncRNA), microRNA (miRNA), and PIWI-interacting RNA (piRNA). As vital members of the intracellular gene regulatory network, they affect various life activities of cells. LncRNA functions as a molecular bait, molecular signal and molecular scaffold in the body through molecular guidance. miRNAs are critical regulators of gene expression; they mainly control the stability or translation of their target mRNA after transcription. piRNA functions mainly through silencing genomic transposable elements and the post-transcriptional regulation of mRNAs in animal germ cells. Current studies have shown that these ncRNAs also play significant roles in the reproductive system and are involved in the regulation of essential cellular events in spermatogenesis and follicular development. The abnormal expression of ncRNA is closely linked to testicular germ cell tumors, poly cystic ovary syndrome and other diseases. This paper briefly presents the research on the reproductive process and reproductive diseases involving ncRNAs.
... According to various published reports, the frequency of Y chromosome microdeletion among infertile male ranges from 1-55% and the average frequency has been reported to be 15% worldwide (Simoni et al. 1999(Simoni et al. , 2004. In the present study, the estimated frequency of Y chromosome microdeletion was 8.5% which is similar to that reported by other investigators from northern region of India (Thangaraj et al. 2003;Dada et al. 2003) but lower than that reported from southern India (11.1%-12.9%) (Sakthivel and Swaminathan 2008). ...
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.
... As one of the most important gonad glands, the testis has multiple functions in male reproduction, such as spermatogenesis and endocrine effects; abnormal testis function can easily cause sexual dysfunction and male infertility (Rodprasert et al. 2020). Further, testicular dysfunction not only leads to a decrease in production efficiency in the breeding industry, which is caused by low fertility of male livestock, but also causes many problems in humans, such as male infertility (Dada et al. 2003). Testicular dysfunction could be repaired using RSV (Archana et al. 2018;Li et al. 2018;de Oliveira et al. 2019), but the underlying mechanism was unclear. ...
This study aimed to analyse global metabolomic changes associated with trans-resveratrol (RSV) treatment in mice with cryptorchidism using untargeted metabolomics. Cryptorchidism was established surgically in Kunming mice, which were then treated with 20µg g-1 day-1, s.c., RSV for 35 consecutive days. Typical manifestations of spermatogenesis arrest were seen in mice with cryptorchidism, and RSV treatment for 35 days restored spermatogenesis. Liquid chromatography-tandem mass spectrometry was used to profile the metabolome of testes from mice in the control (non-cryptorchid, untreated), cryptorchid and RSV-treated cryptorchid groups. In all, 1386 and 179 differential metabolites were detected in the positive and negative modes respectively. Seven and six potential biomarkers were screened for spermatogenesis arrest and restoration respectively. Pathway analysis showed changes in 197 metabolic pathways. The hexosamine biosynthesis pathway was inhibited in the cryptorchid group, which probably resulted in a decrease in the end product, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). Immunoblot analysis showed that total testicular protein O-linked β-N-acetylglucosamine glycosylation was related to spermatogenesis arrest, further indicating a decrease in UDP-GlcNAc in the cryptorchid group. Thus, untargeted metabolomics revealed the biochemical pathways associated with the restoration of metabolic status in the cryptorchid group following RSV treatment and the findings could be used to monitor the response to RSV treatment. This study provides a meaningful foundation for the future clinical application of RSV in the treatment of spermatogenesis dysfunction.
... Infertility is one serious issue that threatens the human reproductive health. According to statistics, on a worldwide scale 15% of married couples are infertile, and infertility factors affect about half of men and women (1). The development of assisted reproductive technology brings hope to many infertile patients. ...
... In early mammalian embryos, genomic transcription is quiescent until ZGA occurs 2-3 days after fertilization. The coding gene of YAP, Yap1, was found to be highly expressed in human and mouse oocytes and early embryos (11,12), and maternally accumulated YAP in oocyte is essential for ZGA (1). The embryos of Yap1 knockout female mice presented prolonged 2-cell stage and slower development into the 4-cell stage. ...
Background: Early embryonic developmental stagnation is one of the reasons that affect the outcome of in vitro fertilization-embryo transfer, leading to the depletion of available embryos or failure after transplantation. It has been shown that defects in the ribonucleotide-reductase lead to cell cycle arrest, developmental delay, and high mutation rates.
Case presentation: Two female patients, who were siblings from an inbreeding family, suffered primary infertility of unknown causes and early embryonic developmental arrest during IVF treatment. A total of 39 oocytes were obtained from the patients in collectively 5 IVF/ICSI cycles, of which 37 were mature eggs, only 2 transplantable embryos were formed, and no pregnancy was achieved. Whole genome sequencing and Sanger sequencing were adopted to identify and confirm variations that might cause early embryo developmental stagnation in this family. We identified a homozygous variant c.262C>T:p.His88Tyr in ribonucleotide-diphosphate reductase subunit M2 (RRM2) in both patients and their parents each carried a heterozygous allele. Pedigree analysis showed an autosomal recessive inheritance pattern. Function of this variant was predicted by online databases, which indicated it to be a potential pathogenic mutation.
Conclusions: We identified RRM2 as a potential causative gene for early embryonic developmental stagnation. It was also suggested that RRM2 might be a maternal effect gene.
