Browsing by Author "Vertika Singh"

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Array-based DNA methylation profiling reveals peripheral blood differential methylation in male infertility
(Elsevier Inc., 2019) Saumya Sarkar; Kumar Mohanty Sujit; Vertika Singh; Rajesh Pandey; Sameer Trivedi; Kiran Singh; Gopal Gupta; Singh Rajender
Objective: To study peripheral blood DNA differential methylation in oligozoospermic infertile men in comparison with normozoospermic fertile controls. Design: Case-control study. Setting: Reproductive biology laboratory. Patients(s): Azoospermic and oligozoospermic infertile patients (n = 6) and normozoospermic fertile controls (n = 6) in the discovery phase, and oligo/asthenozoospermic infertile men (n = 11) and normozoospermic fertile controls (n = 10) in the validation phase. Intervention(s): Blood samples drawn from all participants, DNA isolation and methylation analysis. Main Outcome Measure(s): DNA methylation values analyzed using genomewide methylation 450K BeadChip array, followed by deep sequencing of selected regions for methylation analysis in the neighborhood regions of differentially methylated CpGs. Result(s): We found 329 differentially methylated CpG spots, out of which 245 referred to the genes, representing 170 genes. Deep-sequencing analysis confirmed the methylation pattern suggested by 450K array. A thorough literature search suggested that 38 genes play roles in spermatogenesis (PDHA2, PARP12, FHIT, RPTOR, GSTM1, GSTM5, MAGI2, BCAN, DDB2, KDM4C, AGPAT3, CAMTA1, CCR6, CUX1, DNAH17, ELMO1, FNDC3B, GNRHR, HDAC4, IRS2, LIF, SMAD3, SOD3, TALDO1, TRIM27, GAA, PAX8, RNF39, HLA-C, HLA-DRB6), are testis enriched (NFATC1, NMNAT3, PIAS2, SRPK2, WDR36, WWP2), or show methylation differences between infertile cases and controls (PTPRN2, RPH3AL). Conclusion(s): We found a statistically significant correlation between peripheral blood DNA methylation and male infertility, raising the hope that epigenome-based blood markers can be used for screening male infertility risk. The study also identified new candidates for spermatogenesis and fertility. © 2019 American Society for Reproductive Medicine
Autosomal genes in male infertility
(Springer Singapore, 2017) Vertika Singh; Sandeep Kumar Bansal; Rajender Singh; Kiran Singh
Spermatogenesis is driven by the master genes present on the Y chromosome. These driver genes need support from numerous other genes spread across the genome for a number of actions such as energy metabolism, cell death and apoptosis, protein turnover, synthesis of new proteins and garbage disposal. Preliminary studies on infertility focused on the Y chromosome genes due to their primary and indispensable role in spermatogenesis. A number of other studies on human infertility and mouse knockouts have identified several spermatogenically important genes present on chromosomes other than X and Y. For some of these genes, molecular pathways they participate in have also been worked out. This chapter summarizes the genes present on the autosomes that facilitate the process of spermatogenesis and fertility. © Springer Nature Singapore Pte Ltd. 2017. All rights reserved.
AZF deletions in Indian populations: original study and meta-analyses
(Springer, 2020) Andrabi Syed Waseem; Vertika Singh; Girish Chandra Makker; Sameer Trivedi; Geetanjali Mishra; Kiran Singh; Singh Rajender
Purpose: To identify the frequency of Y chromosome microdeletions in Indian populations and to quantitatively estimate the significance of association between these deletions and male infertility. Methods: A total of 379 infertile males (302 azoospermic and 77 oligozoospermic infertile males) and 265 normozoospermic fertile males were evaluated for Y chromosome microdeletions (YCD) using PCR amplification and gel electrophoresis. Meta-analyses were performed on AZFa (2079 cases and 1217 controls), AZFb (2212 cases and 1267 controls), AZFc (4131 cases and 2008 controls), and AZFb+c (1573 cases and 942 controls) deletions data to quantitatively estimate the significance of association between these deletions and male infertility in Indian populations. Results: The results revealed that out of 379 infertile azoospermic and oligozoospermic males, 38 (10.02%) had AZF deletions. No deletion was found in control samples. The highest percentage of deletions was observed in the AZFc region, followed by AZFa and AZFb. Qualitative analysis showed that AZF deletions were present in 0.59 to 32.62% (average 13.48%) of infertile cases in Indian populations. Meta-analysis revealed a significant association of AZFa (OR = 6.74, p value = 0.001), AZFb (OR = 4.694, p value = 0.004), AZFc (OR = 13.575, p value = 0.000), and AZFb+c (OR = 5.946, p value = 0.018) deletions with male infertility. Conclusion: AZF deletions were seen in 10.02% of azoospermic and oligozoospermic cases with the highest frequency of AZFc deletions. Pooled analysis for all studies showed deletion frequency from 0.59 to 32.62% (average = 13.48%). Meta-analysis showed significant association of AZFa, AZFb, and AZFb+c deletions with male infertility. Analysis of Y chromosome microdeletions should be reckoned as an essential testing for diagnostic and therapeutic purposes. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.
Azoospermic infertility is associated with altered expression of DNA repair genes
(Elsevier B.V., 2019) Vertika Singh; Deepika Jaiswal; Kanhaiya Singh; Sameer Trivedi; Neeraj K Agrawal; Gopal Gupta; Singh Rajender; Kiran Singh
Compelling evidence suggest that germs cells are predominantly sensitive to DNA damaging agents in comparison to other cells. High fidelity DNA repair in testicular cells thus becomes indispensable to preserve the genomic integrity for passing on to the progeny. Compromised DNA repair machinery in the testicular cells may result in impaired spermatogenesis and infertility. It remains unclear if the alterations in the expression of DNA repair genes correlate with azoospermia and male infertility. In the present study, 54 non-obstructive azoospermic infertile patients with hypospermatogenesis (HS, n = 26), maturation arrest (MA, n = 15), Sertoli cell only syndrome (SCOS, n = 13) and 14 controls with obstructive azoospermia, but normal spermatogenesis were recruited. Expression profiling of 84 DNA repair genes in testicular biopsy samples was performed using PCR array. Out of 84 genes, 27, 64 and 28 genes showed >5 fold down-regulation in the HS, MA and SCOS groups, respectively. On the basis of differential expression and their functional significance in spermatogenesis, ten genes (MSH2, BRIP1, CCNH, LIG4, MGMT, NTHL1, PMS1, DMC1, POLB and XPA) were selected for validation of transcript levels in a higher number of cases using RT-PCR, which corroborated the findings of array. Four genes (MSH2, LIG4, PMS1 and DMC1) were analyzed for protein levels using immunohistochemistry, which further validated the loss of DNA repair gene expression. Caspase-3 immunostaining showed that the loss of DNA repair correlated with increased testicular apoptosis in patients. Maturation arrest showed the highest apoptotic index with maximum number of downregulated genes. We conclude that the loss of DNA repair genes expression in testis correlates with increased apoptosis, azoospermia and infertility. © 2019 Elsevier B.V.
Chromosome microarray analysis: A case report of infertile brothers with CATSPER gene deletion
(Elsevier, 2014) Deepika Jaiswal; Vertika Singh; U.S. Dwivedi; Sameer Trivedi; Kiran Singh
We present the case of two brothers who were referred to a male infertility clinic for infertility workup. Conventional chromosome analysis and Y chromosome microdeletions did not reveal any genetic alterations. We utilized the chromosome microarray analysis (CMA) to identify novel and common variations associated with this severely impaired spermatogenesis cases. CMA specific results showed a common deletion in the 15q15.3 region that harbors genes like CATSPER2, STRC and PPIP5K1 in both cases (M18 and M19). In addition we identified small duplication in X and 11 chromosomes of M19. This is the first familial case report from India on occurrence of CATSPER gene deletion in human male infertility. © 2014 Elsevier B.V.
Cytogenetic factors in male infertility
(Springer Singapore, 2017) Vertika Singh; Kiran Singh
Nearly 15% of the couples worldwide face the problem of infertility. A number of cytogenetic aberrations in the form of somatic chromosome aneuploidies, sperm aneuploidies, chromosomal translocations and inversions, etc. are known to contribute to male infertility. Couples with normal hormonal profile should be evaluated for possible cytogenetic abnormalities before proceeding to treatment. The identification of cytogenetic abnormality cannot only explain infertility but also guide treatment in the affected cases. This chapter summarizes the cytogenetic factors that increase the risk of male infertility. Towards the end, we have provided a glimpse of the contemporary techniques that have revolutionized the classical field of cytogenetics. © Springer Nature Singapore Pte Ltd. 2017. All rights reserved.
Duplications in 19p13.3 are associated with male infertility
(Springer New York LLC, 2019) Vertika Singh; Renu Bala; Arijit Chakraborty; Singh Rajender; Sameer Trivedi; Kiran Singh
Purpose: To identify genomic imbalances and candidate loci in idiopathic male infertility. Methods: Affymetrix CytoScan 750K Array was used to analyze genomic imbalances and candidate loci in 34 idiopathic infertile cases of different phenotypes (hypo-spermatogenesis, n = 8; maturation arrest, n = 7; and Sertoli cell-only syndrome, n = 13, severe oligozoospermia, n = 6, and 10 normozoospermic fertile men). Ten ethnically matched controls were screened for comparison. Results: The cytogenetic array analysis detected a genomic gain at the 19p13.3 region in 9 (26.47%) cases, with the highest frequency in patients with Sertoli cell-only syndrome (SCOS) (38%). Its complete absence in the control group suggests its likely pathogenic nature. In addition to Y-classical, micro, and partial deletions, the duplication in 19p13.3 could serve as a unique biomarker for evaluation of infertility risk. The common region across the individuals harboring the duplication identified STK11, ATP5D, MIDN, CIRBP, and EFNA2 genes which make them strong candidates for further investigations. The largest duplicated region identified in this study displayed a major network of 7 genes, viz., CIRBP, FSTL3, GPX4, GAMT, KISS1R, STK11, and PCSK4, associated with reproductive system development and function. The role of chance was ruled out by screening of ethnically matched controls. Conclusion: The result clearly indicates the significance of 19p13.3 duplication in infertile men with severe testicular phenotypes. The present study underlines the utility and significance of whole genomic analysis in the cases of male infertility which goes undiagnosed due to limitations in the conventional cytogenetic techniques and for identifying genes that are essential for spermatogenesis. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
Environment, Lifestyle, and Female Infertility
(Springer Science and Business Media Deutschland GmbH, 2021) Renu Bala; Vertika Singh; Singh Rajender; Kiran Singh
Lifestyle factors, which include the practices we adopt in our daily life, have a significant role in shaping our overall health. These lifestyle choices are mainly centered on personal preferences and our surrounding social environment. In addition to lifestyle factors, we continuously interact with our environment, which impacts physiology. Several factors have been claimed to affect women’s fertility; lifestyle-related factors, in particular, have received great attention in the last decade. Due to societal and professional pressure, childbearing age in women has gradually shifted to the 30s. Delayed age of childbearing along with modern lifestyle offers a wider window of opportunity for various lifestyle and genetic perturbations to penetrate to affect fertility. While clinical studies have strengthened a direct correlation between lifestyle, environment, and female reproductive health; experimental studies on animal models have investigated their mechanism of action. In most instances, these factors target the neuroendocrine pathways, resulting in metabolic derangements. This review aims to dissect the plausible interconnection of lifestyle and environmental factors with various neuroendocrine pathways and to discuss how it can affect the female physiology in the long-term, resulting in reproductive incompetence. © 2020, Society for Reproductive Investigation.
Excess iodine impairs spermatogenesis by inducing oxidative stress and perturbing the blood testis barrier
(Elsevier Inc., 2020) Arijit Chakraborty; Vertika Singh; Kiran Singh; Singh Rajender
Approximately 2 billion people worldwide are susceptible to iodine deficiency. Iodine deficiency has largely been tackled by iodine fortification in salt; however indiscriminate use of iodine raises the risk of iodine toxicity. In this study, we aimed to investigate the molecular mechanisms underlying adverse effect of excess iodine on spermatogenesis. Sprague Dawley (SD) rats were orally administered with 0.7 mg potassium iodide (KI)/100 g Bw and 3.5 mg potassium iodide (KI)/100 g Bw for a period of 60 days. This resulted in significant loss of sperm count and motility. Molecular investigations provided evidence for the generation of oxidative stress with high SOD levels, reduced Nrf2, HO-1 and increased NF-kB and Follistatin. Further investigations showed increased apoptosis evidenced by reduced expression of anti-apoptotic (BCL-2, Survivin), increased expression of pro-apoptotic (Bid, Bax) markers, and increased expression of p53 and other modulators/effectors of apoptosis (cytochrome c, cleaved PARP, caspase3 and caspase9). Analysis of the blood testis barrier proteins showed reduced expression of tight junction (JAM-A, Tricellulin), ectoplasmic specialization (Integrin- β1), adherens junction (N-Cadherin, E-cadherin, β-catenin) proteins, and reduced expression of other junction protein coding genes (Claudin1, Claudin 5, Occludin, ZO-1, Testin, Fibronectin, CAR-F). Focal adhesion kinase (FAK) and key regulators of spermatogenesis (c-Kit receptor, androgen receptor) were also parallelly decreased. Further investigation showed reduced expression of germ cell proliferation and differentiation markers (PCNA, Cyclin D1, c-Kit, Cdk-4). These findings collectively explain the loss of spermatogenesis under excess iodine conditions. In conclusion, excess iodine causes loss of spermatogenesis by inducing oxidative stress and disrupting the blood testis barrier and cytoskeleton. © 2020
Fertilization failure and gamete health: Is there a link?
(Frontiers in Bioscience, 2017) Snehil Budhwar; Vertika Singh; Priyanka Verma; Kiran Singh
Fertilization is a hallmark event of sexual reproduction marked by the fusion of male and female gamete to form zygote. It is a highly complex, yet a robust process that is intricately regulated by various signalling molecules. A healthy fertilization is determined by the quality of zygote which is contingent on the health of egg and sperm. The relationship between infertility and gametic health can be reciprocal. On one hand gametogenesis has to be dynamic and unremitting to sustain the reproductive health, while on the other hand it has to be error free for proper embryonic development. Complex cellular interactions make gametogenesis highly vulnerable to extrinsic as well as intrinsic intrusions. Molecular disparities during these phases may result in complete fertilization failure. Present review provides an overview of the regulation of gametogenesis, determinants of healthy gamete, players at fertilization window and what may go wrong during the development of zygote to embryo leading to implantation failure. We have outlined different 'windows' of vulnerability during gametogenesis supported by evidences affecting the fertility potential of both the partners.
Genome-wide differential methylation analyses identifies methylation signatures of male infertility
(Oxford University Press, 2018) Kumar Mohanty Sujit; Saumya Sarkar; Vertika Singh; Rajesh Pandey; Neeraj Kumar Agrawal; Sameer Trivedi; Kiran Singh; Gopal Gupta; Singh Rajender
STUDY QUESTION: Do methylation changes in sperm DNA correlate with infertility? STUDY ANSWER: Loss of spermatogenesis and fertility was correlated with 1680 differentially-methylated CpGs (DMCs) across 1052 genes. WHAT IS KNOWN ALREADY: Methylation changes in a number of genes have been correlated with reduced sperm count and motility. STUDY DESIGN, SIZE, DURATION: This case-control study used spermatozoal DNA from 38 oligo-/oligoastheno-zoospermic infertile patients and 26 normozoospermic fertile men. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Genome-wide methylation analysis was undertaken using 450 K BeadChip on spermatozoal DNA from six infertile and six fertile men to identify DMCs. This was followed by deep sequencing of spermatozoal DNA from 32 infertile patients and 20 fertile controls. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1680 DMCs were identified, out of which 1436 were hypermethylated and 244 were hypomethylated. Classification of DMCs according to the genes identified BCAN, CTNNA3, DLGAP2, GATA3, MAGI2 and TP73 among imprinted genes, SPATA5, SPATA7, SPATA16 and SPATA22 among spermatogenesis-associated genes, KDM4C and JMJD1C, EZH2 and HDAC4 among genes which regulate methylation and gene expression, HLA-C, HLA-DRB6 and HLA-DQA1 among complementation and immune response genes, and CRISPLD1, LPHN3 and CPEB2 among other genes. Genes showing significant differential methylation in deep sequencing, i.e. HOXB1, GATA3, EBF3, BCAN and TCERG1L, are strong candidates for further investigations. The role of chance was ruled out by deep sequencing of select genes. LARGE-SCALE DATA: N/A. LIMITATIONS, REASON FOR CAUTION: Genome-wide analyses are fairly accurate, but may not be exactly validated in replication studies across all DMCs. We used the 't' test in the genome-wide methylation analysis, whereas other tests could provide a more robust and powerful analysis. WIDER IMPLICATIONS OF THE FINDINGS: DMCs can serve as markers for inclusion in infertility screening panels, particularly those in the genes showing differential methylation consistent with previous studies. The genes validated by deep sequencing are strong candidates for investigations of their roles in spermatogenesis.STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Council of Scientific and Industrial Research (CSIR), Govt. of India with grant number BSC0101 awarded to Rajender Singh. None of the authors has any competing interest to declare. © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
Genomic landscape of human Y chromosome and male infertility
(Springer Singapore, 2017) Vertika Singh; Kiran Singh
Initially thought to be functionally inert, the Y chromosome has now been established not only as a regulator organizer of sex determination and a functional hub for spermatogenesis but also as a genetic center involved in mediating autosomal functions and genome-wide expressions. The whole genome and transcriptome analysis of Y chromosome across different species have shed light on the origin, comparative gene content, and long-term providence of this interesting chromosome. Comparative studies further provided insights into the evolutionary and molecular forces driving Y degeneration toward evolutionary destiny. In the due course of evolution, the Y chromosome has undergone dynamic transformations and has evolved autonomously, gaining a lot of distinctive characteristics that no other chromosome possesses. An unusual architecture and dynamic nature has made it the most remarkable chromosome for genetic and molecular studies. © Springer Nature Singapore Pte Ltd. 2017. All rights reserved.
HPG axis: The central regulator of spermatogenesis and male fertility
(Springer Singapore, 2017) Vertika Singh; Neeraj Kumar Agrawal; Rajesh Verma; Kiran Singh
Pituitary gonadotropins have been established as essential components for the differentiation of the male reproductive organs. Human sexual maturation and spermatogenesis are intricately regulated by the hypothalamic-pituitary-gonadal (HPG) axis, which eventually determines the reproductive potential of an organism. Alterations affecting this fine balance can severely impair sexual development and fertility. These defects may result from mutations, small deletions or polymorphic changes within the regulatory genes involved in the biosynthesis of hormones, hormone receptors, growth factors and their associated signal transduction pathways. This present chapter summarizes the functioning and regulation of the HPG axis, its control over spermatogenesis by means of FSH and LH synthesis, and the impact of endocrine disruptors on this central axis regulating fertility. © Springer Nature Singapore Pte Ltd. 2017. All rights reserved.
Hyperhomocysteinemia and low vitamin B12 are associated with the risk of early pregnancy loss: A clinical study and meta-analyses
(Elsevier Inc., 2021) Renu Bala; Rachna Verma; Priyanka Verma; Vertika Singh; Namrata Yadav; Singh Rajender; Nisha Rani Agrawal; Kiran Singh
One-carbon metabolism is crucial for the maintenance of healthy pregnancy and alterations in this pathway have been associated with various pregnancy-related complications. Therefore, the present study was conducted to test the hypothesis that the altered folic acid, vitamin B12 and homocysteine levels are associated with the risk of early pregnancy loss (EPL). Plasma folic acid, vitamin B12 and homocysteine levels were analyzed in 83 females with EPL and 70 healthy pregnant females in their first trimester. Further, meta-analyses of folic acid, vitamin B12 and homocysteine were also performed involving various eligible studies. Results from our case-control study and meta-analysis showed that folic acid deficiency is not associated with the risk of EPL. On the other hand, low vitamin B12 and hyperhomocysteinemia were individually found to be significant risk factors for EPL in the present study (P < .01, P < .05, respectively) and meta-analysis as well (P < .001, P < .05, respectively). Vitamin B12 deficiency in combination with hyperhomocysteinemia was a more serious risk factor for EPL (Odds Ratio = 4.98, P = 0.002). Therefore, we conclude that vitamin B12 deficiency and elevated homocysteine levels are independent risk factors for EPL, and of higher risk when combined. The assessment of vitamin B12 and homocysteine levels may serve as a good screening marker for EPL risk. © 2021 Elsevier Inc.
Impact of socio-demographic variables on antenatal services in eastern Uttar Pradesh, India
(Taylor and Francis Ltd., 2021) Renu Bala; Ajay Singh; Vertika Singh; Priyanka Verma; Snehil Budhwar; Om Prakash Shukla; Gyan Prakash Singh; Kiran Singh
We investigated the impact of socio-demographic variables on antenatal care (ANC) utilization and the low birth weight of a child. Data were collected from 300 pregnant females. Only 22.5% of females received full antenatal care (≥4 visits). Our results showed that female’s age at marriage and education plays a significant role in improving ANC. We observed an overall decrease in the utilization of services provided during each antenatal visit. ANC visits from the first trimester decrease the risk of having a baby with low birth weight. Awareness programs and educating families about pregnancy care are recommended to improve ANC utilization. © 2020 Taylor & Francis Group, LLC.
Increased DNA methylation in the spermatogenesis-associated (SPATA) genes correlates with infertility
(Blackwell Publishing Ltd, 2020) Kumar Mohanty Sujit; Vertika Singh; Sameer Trivedi; Kiran Singh; Gopal Gupta; Singh Rajender
Background: Spermatogenesis-associated (SPATA) family of genes plays important roles in spermatogenesis, sperm maturation or fertilization. The knockout studies in mice have demonstrated that SPATA genes are crucial for fertility. Gene expression and genetic polymorphism studies have further suggested their correlation with infertility; however, methylation analysis of SPATA genes in human male infertility has not yet been undertaken. Objectives: To analyze the methylation status of SPATA4, SPATA5 and SPATA6 genes in oligozoospermic male infertility. Materials and methods: In the present study, we have analyzed DNA methylation pattern in the promoter regions of SPATA4, SPATA5 and SPATA6 genes in oligozoospermic patients and compared it with normozoospermic fertile controls. Semen samples were obtained from 30 oligozoospermic infertile and 19 normozoospermic fertile controls, and DNA methylation levels of the target gene promoters were analyzed by amplicon based deep sequencing methylation analysis using MiSeq. Results: SPATA4 (P < 0.0008), SPATA5 (P = 0.009) and SPATA6 (Promoter, P < 0.0005; Exon 1, P = 0.0128) genes were significantly hypermethylated in oligozoospermic patients in comparison to controls. This is the first study reporting a higher methylation in the promoters of SPATA4, SPATA5 and SPATA6 in oligozoospermic infertile individuals in comparison to the normozoospermic fertile controls. Discussion: Altered methylation of SPATA genes would affect pathways involved in sperm production or affect various processes linked to sperm fertility. Conclusion: In conclusion, hypermethylation in the SPATA4, SPATA5 and SPATA6 genes correlates with oligozoospermic infertility. © 2019 American Society of Andrology and European Academy of Andrology
Interleukin-17 gene polymorphisms and the risk of early miscarriage: A case-control study and meta-analysis
(Elsevier B.V., 2018) Priyanka Verma; Rohini R. Nair; Snehil Budhwar; Vertika Singh; Renu Bala; Anuradha Khanna; Nisha R. Agarwal; Punam Rai; Singh Rajender; Kiran Singh
Previous reports clearly suggest that IL-17 have important role in development of systemic and peripheral inflammation in early miscarriage (EM). In the present study, we have investigated the association between genetic variants in IL-17A, IL-17F and susceptibility to EM. We recruited 135 EM patients and 150 controls and used PCR-RFLP method for genotyping the polymorphisms of IL-17A, rs4711998 (−832 A/G), rs8193036 (−692C/T) and IL-17F rs763780 (7488 T/C). No significant difference was observed for all the three polymorphic sites between the EM patients and control group in terms of genotypic (rs4711998, χ2 = 1.95, p = 0.37; rs8193036, χ2 = 1.91, p = 0.38; rs763780, χ2 = 2.45, p = 0.29), and allelic frequencies (rs4711998, OR = 1.19, 95% CI = 0.84 to 1.67, p = 0.35; rs8193036,OR = 1.18, 95% CI = 0.58 to 2.06, p = 0.75; rs763780, OR = 1.5, 95% CI = 0.93 to 2.71, p = 0.11). Further, meta-analysis of IL-17F (rs763780) variant with EM also revealed non-significant association of IL-17F (rs763780) variant with EM in the presence of mutant genotype (CC) via random effect model (p = 0.70, OR = 1.30, 95% CI =0.33–5.11). © 2018
Is MTHFR 677 C>T polymorphism clinically important in Polycystic Ovarian Syndrome (PCOS)? A case-control study, meta-analysis and trial sequential analysis
(Public Library of Science, 2016) S. Justin Carlus; Saumya Sarkar; Sandeep Kumar Bansal; Vertika Singh; Kiran Singh; Rajesh Kumar Jha; Nirmala Sadasivam; Sri Revathy Sadasivam; P.S. Gireesha; Kumarasamy Thangaraj; Singh Rajender
Background: Optimum efficiency of the folate pathway is considered essential for adequate ovarian function. 677 C>T substitution in the 5, 10-methylene tertrahydrofolatereductase (MTHFR) gene compromises activity of the MTHFR enzyme by about 50%. The significance of correlation between 677C>T substitution and PCOS remains dubious due to the low power of published studies. Methods and Results: We analyzed MTHFR 677 C>T site in ethnically two different PCOS case-control groups (total 261 cases and 256 controls) from India. The data analysis revealed a lack of association between this polymorphism and PCOS [OR = 1.11 (95%CI = 0.71-1.72), P = 0.66]. Group-wise analysis on the basis of ethnicity also revealed no association in any of the ethnic groups [Indo-Europeans, P = 1; Dravidians, P = 0.70]. Homocysteine levels did not differ significantly between cases (15.51 μmol/L, SD = 2.89) and controls (15.89 μmol/L, SD = 2.23). We also undertook a meta-analysis on 960 cases and 1028 controls, which suggested a significant association of the substitution with PCOS in the dominant model of analysis (OR = 1.47 (95%CI = 1.04-2.09), P = 0.032]. Trial sequential analysis corroborated findings of the traditional meta-analysis. However, we found that the conclusions of meta-analysis were strongly influenced by studies that deviated from the Hardy Weinberg equilibrium. A careful investigation of each study and a trial sequential analysis suggested that 677 C>T substitution holds no clinical significance in PCOS in most of the populations. Conclusion: In conclusion, MTHFR 677 C>T polymorphism does not affect PCOS risk in India. The association seen in the meta-analysis is due to an outlier study and studies showing deviation from the Hardy Weinberg equilibrium. © 2016 Carlus et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sex chromosomal genes in male infertility
(Springer Singapore, 2017) Sandeep Kumar Bansal; Vertika Singh; Kiran Singh; Rajender Singh
Y chromosome harbors the male-specific region (MSY) that regulates male sex determination and spermatogenesis. Y microdeletions are the most common cause of male infertility. These deletions are found in 15-20% of patients with idiopathic azoospermia and 7-10% of patients with severe oligozoospermia. Apart from microdeletions, partial deletions in the AZFc region result in loss of multiple copies of Y genes and increase the risk of infertility. A few studies have suggested that routine screening of these deletions could help in understanding the etiology, offering counseling and managing infertility by natural or assisted methods. X being a homologue chromosome of Y has drawn attention regarding the presence of spermatogenic genes. A number of theories and speculations have been put forward that are now supported by the identification of a number of testis-specific or testis-predominant genes present on the X chromosome. This chapter provides an overview of the Y deletions and X chromosome genes that affect spermatogenesis or male fertility. © Springer Nature Singapore Pte Ltd. 2017. All rights reserved.
SNPs in ERCC1, ERCC2, and XRCC1 genes of the DNA repair pathway and risk of male infertility in the Asian populations: association study, meta-analysis, and trial sequential analysis
(Springer New York LLC, 2019) Vertika Singh; Sandeep Kumar Bansal; D.V.S. Sudhakar; Neelabh; Arijit Chakraborty; Sameer Trivedi; Gopal Gupta; Kumarasamy Thangaraj; Singh Rajender; Kiran Singh
Purpose: We investigated if substitutions in the ERCC1, ERCC2, and XRCC1 genes of the DNA repair pathway correlate with non-obstructive azoospermia and male infertility. Methods: A total of 548 azoospermic infertile males and 410 fertile controls were genotyped for XRCC1 399A > G, 280G > A, and ERCC1 C > A 3′ UTR and 541 azoospermic infertile males and 416 fertile controls were genotyped for ERCC2 751A > C using iPLEX Gold Assay. Meta-analyses were performed on XRCC1 399A > G (1022 cases and 1004 controls), ERCC1 C > A 3′ UTR (879 cases and 1059 controls), and ERCC2 751A > C (914 cases and 850 controls) polymorphisms to quantitatively estimate the significance of the association between these polymorphisms and the risk of infertility. Results: Statistically significant association between ERCC2 751A > C SNP and male infertility was found using the codominant model (p = 0.03). Results of meta-analysis suggested a lack of correlation with male infertility risk, which could be due to pooling of studies from different ethnic populations. Due to limited the number of studies, a stratified analysis for different ethnic groups could not be performed. Conclusion (s): In conclusion, AA genotype of 751A > C SNP in ERCC2 correlated with a higher risk of male infertility and may contribute to an increased risk of azoospermia and male infertility in Indian men. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.