Faisel Ahmad , Mahrukh Hameed Zargar , Mohammad Lateef , Arshad Hussain , Tahir Mohuiddin Malla , Mohd Ashraf Ganie , Iqbal Qasim , Sajad Ul Islam Mir , Saima Wani , Nadia Khurshid
{"title":"Azoospermia factor gene microdeletions in infertile men with non-obstructive azoospermia and normal karyotype: First case-control study from Kashmir","authors":"Faisel Ahmad , Mahrukh Hameed Zargar , Mohammad Lateef , Arshad Hussain , Tahir Mohuiddin Malla , Mohd Ashraf Ganie , Iqbal Qasim , Sajad Ul Islam Mir , Saima Wani , Nadia Khurshid","doi":"10.1016/j.genrep.2024.102064","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Micro-deletions in the Y chromosome are recognized as the causative factor for male infertility. The prevalence of Y chromosome micro-deletions exhibits variation among infertile males across different areas and races globally. The study of Y chromosome micro- deletions is crucial among genetic variables owing to their ability to transmit genetic defects to the progeny. Microdeletion of the azoospermia factor (AZF) region associated with the long arm of the Y chromosome (Yq) has three sub-regions (AZFa, AZFb, and AZFc) that play an important role in spermatogenesis. The genes associated with the AZF region of the Y chromosome are believed to play a crucial role in the process of spermatogenesis by performing several activities such as gene silencing, transcription, ubiquitination, and maintenance of microtubule networks. Due to the absence of epidemiological research on Y chromosome micro-deletions in ethnic infertile male population of Kashmir, our study sought to examine the Y chromosome micro-deletions among non-obstructive azospermic infertile men in Kashmir.</div></div><div><h3>Objective</h3><div>The research was aimed to establish the frequency and characteristics of micro-deletions in the AZF region of Y chromosome in infertile males of our population with non-obstructive Azoospermia and normal Karyotype.</div></div><div><h3>Methods</h3><div>A total of 120 subjects were included in the study. Samples from 60 male patients with fertility issues (non-obstructive azoospermia) and an equal number of samples from normal men having established fatherhood (biological fathers) were taken for the study. The average age in years of cases and controls were 32.80 and 34.88 respectively. A total of 26.66 % of cases and 13.33 % of controls were found to be consanguineous, 36.66 % of cases and 40 % of controls were urban while 63.33 % of cases and 60 % of controls were from rural population. Molecular analysis was performed by multiplex polymerase chain reactions (PCR) using sequence tagged sites (STS) from 3 different regions of AZF of Y chromosome. To assess the frequency of AZF micro-deletions, molecular analysis was performed by multiplex polymerase chain reactions (PCR) using sequence tagged sites (STS) from 3 different regions of the Y chromosome (sY84 and sY86 for AZFa region; sY127 and sY134 for AZFb; sY254 and sY255 for AZFc region).</div></div><div><h3>Results</h3><div>In the present study a total of 9 out of 60 cases (15 %) were found to have Y chromosome micro- deletions in AZF region of Yq arm. The most frequent micro deletions were observed in AZF<sub>b</sub> region, 8 out of 60 cases (13.33 %) from AZF<sub>b</sub> region were found to have deletions.5 out of 60 cases (8.33 %) were reported with deletions associated to AZFc region region and 6.66 % of cases were found to harbor deletions in both AZF<sub>b</sub> and AZF<sub>c</sub> region. However no deletion was reported in the AZFa region in all the studied cases. No micro-deletions were reported in the controls during the study.</div></div><div><h3>Conclusion</h3><div>The study represents the first report on the incidence of Y chromosome microdeletions in infertile men from our population. The findings from the present study indicate the prevalence of these gene microdeletions as a major contributing factor to the etiology of infertility in males. This study emphasizes that the multiplex PCR based screening is a reliable method in ruling Y chromosome micro deletions as a factor in the pathogenicity of male infertility and recommends genetic testing prior to planning of any reproductive assistance.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102064"},"PeriodicalIF":1.0000,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gene Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2452014424001870","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Micro-deletions in the Y chromosome are recognized as the causative factor for male infertility. The prevalence of Y chromosome micro-deletions exhibits variation among infertile males across different areas and races globally. The study of Y chromosome micro- deletions is crucial among genetic variables owing to their ability to transmit genetic defects to the progeny. Microdeletion of the azoospermia factor (AZF) region associated with the long arm of the Y chromosome (Yq) has three sub-regions (AZFa, AZFb, and AZFc) that play an important role in spermatogenesis. The genes associated with the AZF region of the Y chromosome are believed to play a crucial role in the process of spermatogenesis by performing several activities such as gene silencing, transcription, ubiquitination, and maintenance of microtubule networks. Due to the absence of epidemiological research on Y chromosome micro-deletions in ethnic infertile male population of Kashmir, our study sought to examine the Y chromosome micro-deletions among non-obstructive azospermic infertile men in Kashmir.
Objective
The research was aimed to establish the frequency and characteristics of micro-deletions in the AZF region of Y chromosome in infertile males of our population with non-obstructive Azoospermia and normal Karyotype.
Methods
A total of 120 subjects were included in the study. Samples from 60 male patients with fertility issues (non-obstructive azoospermia) and an equal number of samples from normal men having established fatherhood (biological fathers) were taken for the study. The average age in years of cases and controls were 32.80 and 34.88 respectively. A total of 26.66 % of cases and 13.33 % of controls were found to be consanguineous, 36.66 % of cases and 40 % of controls were urban while 63.33 % of cases and 60 % of controls were from rural population. Molecular analysis was performed by multiplex polymerase chain reactions (PCR) using sequence tagged sites (STS) from 3 different regions of AZF of Y chromosome. To assess the frequency of AZF micro-deletions, molecular analysis was performed by multiplex polymerase chain reactions (PCR) using sequence tagged sites (STS) from 3 different regions of the Y chromosome (sY84 and sY86 for AZFa region; sY127 and sY134 for AZFb; sY254 and sY255 for AZFc region).
Results
In the present study a total of 9 out of 60 cases (15 %) were found to have Y chromosome micro- deletions in AZF region of Yq arm. The most frequent micro deletions were observed in AZFb region, 8 out of 60 cases (13.33 %) from AZFb region were found to have deletions.5 out of 60 cases (8.33 %) were reported with deletions associated to AZFc region region and 6.66 % of cases were found to harbor deletions in both AZFb and AZFc region. However no deletion was reported in the AZFa region in all the studied cases. No micro-deletions were reported in the controls during the study.
Conclusion
The study represents the first report on the incidence of Y chromosome microdeletions in infertile men from our population. The findings from the present study indicate the prevalence of these gene microdeletions as a major contributing factor to the etiology of infertility in males. This study emphasizes that the multiplex PCR based screening is a reliable method in ruling Y chromosome micro deletions as a factor in the pathogenicity of male infertility and recommends genetic testing prior to planning of any reproductive assistance.
Gene ReportsBiochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.30
自引率
7.70%
发文量
246
审稿时长
49 days
期刊介绍:
Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.