Browsing by Author "Deepika Jaiswal"

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Association of interleukin-1beta C + 3953T gene polymorphism with human male infertility
(2013) Deepika Jaiswal; Sameer Trivedi; Neeraj K. Agrawal; Rajendra Singh; Kiran Singh
Cytokines are involved in the regulation of spermatogenesis likely mediating the crosstalk among Sertoli and germ cells to facilitate germ cell movement across the seminiferous epithelium during cellular events such as germ cell differentiation. Members of the Interleukin-1 (IL-1) family are pleiotropic cytokines that are involved in inflammation, immunoregulation, and other homeostatic functions. Interleukin-1 alpha (IL-1α), IL-1β, and the IL-1 antagonistic molecule (IL-1 Ra) are present in the testis under normal homeostasis and they further increase upon infection/inflammation. In the present study we have examined the association of C + 3953T polymorphism of the human IL-1B gene with human male infertility. The case control study comprised of two groups: 222 infertile patients and 230 fertile healthy control men. Genotyping for SNP C + 3953T IL-1B was carried out by polymerase chain reaction followed by analysis with specific endonucleases (PCR-RFLP). DNA sequencing was used to validate the PCR-RFLP results. The genotype frequencies of the IL-1B Taq C/T polymorphism were compared between infertile men and controls. The frequency was significantly higher in asthenozoospermic patients compared to fertile control men (odds ratio = 10.4, CI: 2.50- 43.96, p = 0.001). The C + 3953T of the IL-1B gene is associated with male infertility risk in the asthenozoospermic patients from an Indian population. © 2013 Informa Healthcare USA, Inc.
Association of polymorphism in cell death pathway gene FASLG with human male infertility
(Elsevier (Singapore) Pte Ltd, 2015) Deepika Jaiswal; Sameer Trivedi; Neeraj K Agrawal
Objective: To investigate -844C>T single nucleotide polymorphism (SNP) present in the promoter of cell death pathway gene FASLG with male infertile phenotype. Methods: Genotyping for SNP FASLG (rs763110) was done by polymerase chain reaction followed by analysis with specific endonuclease (PCR-RFLP). DNA sequencing was used to ascertain PCR-RFLP results. Results: FASLG -844C>T polymorphism, allele and genotype distribution did not differ significantly between patients and controls (OR: 1.03, 95% CI= 0.7638 to 1.3952, P=0.83). Thus SNP-844C>T of the FASLG gene is not associated with male infertility risk in the analyzed patients. Conclusions: Human male infertility is a complex disorder and thus other genetic or environmental factors may be contributing to the complex etiology, and further study in other region of Indian populations will verify whether it is associated with male infertility risk. © 2015 Hainan Medical College.
Association of the IL1RN Gene VNTR Polymorphism with Human Male Infertility
(2012) Deepika Jaiswal; Sameer Trivedi; Rajendra Singh; Rima Dada; Kiran Singh
Interleukin-1 (IL-1) is a regulatory cytokine that plays an important role in the maintenance of the immune environment of the testis, regulation of junction dynamics and cell differentiation during spermatogenesis. Members of the IL-1 family are pleiotropic cytokines that are involved in inflammation, immunoregulation and other homeostatic functions in the body. IL-1α, IL-1β, and the IL-1 receptor antagonistic molecule (IL-1 Ra) are expressed in the testis under normal homeostasis and they further increase upon infection/inflammation. In the present study we have examined the association of Variable Number Tandem Repeats (VNTR) polymorphism of the Interleukin-1 receptor antagonist gene (IL1RN) with human male infertility. The case-control study comprised of two groups: 331 idiopathic infertile patients and 358 fertile healthy men. The study indicates risk of IL1RN2 variant with male infertility (OR: 1.43, CI: 1.1546 to 1.7804, P = 0.001). To our best knowledge, this is the first report that links IL1RN VNTR polymorphism with human male infertility. © 2012 Jaiswal et al.
Association of the patterns of global DNA methylation and expression analysis of DNA methyltransferases in impaired spermatogenic patients
(Elsevier (Singapore) Pte Ltd, 2015) Deepika Jaiswal; Sameer Trivedi; Neeraj K. Agrawal; Kiran Singh
Objective: To analyze global DNA methylation along with DNA methyltransferases (DNMTs) expression at transcript level in patients with impaired spermatogenesis to dissect its role in pathophysiology of human male infertility. Method: The content of Global methylated cytosine (mC) was determined using ELISA system (Imprint Methylated DNA Quantification Kit, Sigma-Aldrich) in 31 testicular biopsies showing impaired spermatogenesis and 8 with normal spermatogenesis. Real-time reverse transcription-polymerase chain reaction was done to analyze DNMTs (DNMT1, DNMT3A, DNMT3B and DNMT3L) mRNA levels in biopsies with different testicular phenotypes. Results: There was significant increase in levels of global methylation in different impaired testicular phenotypes as compared to normal. Expression analysis revealed significantly increased expression of DNMT1 and its positive correlation with global DNA methylation. Conclusion: In conclusion, increased levels of global methylation in impaired cases might be the one of the contributing factors for aberrant gene expression in infertile patients. © 2015 The Authors.
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.
Combined effect of GSTT1 and GSTM1 polymorphisms on human male infertility in North Indian population
(2012) Deepika Jaiswal; Ravindra Sah; Neeraj K. Agrawal; U.S. Dwivedi; Sameer Trivedi; Kiran Singh
Genes of different pathways regulate spermatogenesis, and complexity of spermatogenic process indicates that polymorphisms or mutations in these genes could cause male infertility. Detoxification pathway is involved in the regulation of spermatogenesis by reducing oxidative stress and contributes to the maintenance of global methylation in concert with other pathways. Glutathione S-transferases (GSTs) belong to the family of phase II antioxidant enzymes involved in the cellular detoxification of various physiological substances. Glutathione S-transferases act as an antioxidant and protect spermatozoa from oxidative stress. Increase in the levels of reactive oxygen species (ROS) along with reduced activity of GSTs may result in sperm membrane damage and DNA fragmentation. A case-control study was done to elucidate the role of deletion polymorphism of GSTT1 and GSTM1 genes from GSTs family on idiopathic human male infertility. The study comprises 2 groups: 113 nonobstructive azoospermia patients and 91 healthy fertile controls. Genomic DNA was analyzed by polymerase chain reaction for GSTT1 and GSTM1 genes. The study showed statistically significant protective association of GSTT1 null genotype with human male infertility (odds ratio [OR]: 0.3, 95% confidence interval [CI] 0.143-0.9966, P =.048) but not with GSTM1 null genotype (OR: 0.66, 95% CI 0.3653-1.2234, P =.19). Also, combination of null genotypes of GSTM1 and GSTT1 confers protective effect (OR: 0.28, CI 0.0801-0.948; P =.04). Probably, individuals bearing GSTM1 and GSTT1 (-/-) genotypes may have protective effect by gene-gene interaction mechanism. In summary, our study underscores the significance of combined effect of GSTT1 and GSTM1 null genotypes in modulating the risk of male infertility. © The Author(s) 2012.
Dysregulation of apoptotic pathway candidate genes and proteins in infertile azoospermia patients
(Elsevier Inc., 2015) Deepika Jaiswal; Sameer Trivedi; Neeraj K. Agrawal; Kiran Singh
Objective To dissect the role of the apoptotic pathway and its regulation in the pathogenesis of male infertility in nonobstructive azoospermia. Design Prospective study. Setting University hospital. Patient(s) Sixty-three infertile azoospermic patients with different histologic phenotypes were recruited (obstructive azoospermia, n = 16; hypospermatogenesis, n = 11; maturation arrest, n = 15; Sertoli cell only, n = 21). Intervention(s) Testicular biopsies for histopathologic and expression analysis. Main Outcome Measure(s) Expression analysis by quantitative reverse transcription-polymerase chain reaction, protein localization by immunohistochemistry and apoptotic proteome array. Result(s) Results showed significantly increased expression of proapoptotic proteins like BAX, BAD, and BAK and comparatively lowered expression of antiapoptotic BCL2 and BCLW. Immunostaining revealed increased active caspase-3 activity and more TUNEL-positive cells in different impaired phenotypes as compared with normal. In addition, significantly increased m-RNA expression of TGFB1, P53, and FASLG along with significant down-regulation of VEGFA were observed. Expression of phosphorylated P53 at the S15 position and phosphorylated RAD17 at S635 was observed in cases with spermatogenic impairment at the translational level. Conclusion(s) The results clearly indicate increased levels of apoptosis along with its other regulatory factors. The balance between pro- (BAX and BAK) and antiapoptotic (BCL2 and BCLW) genes was disturbed, which may lead to altered apoptosis. Therefore, altered regulation of apoptosis might be associated with impaired spermatogenesis, eventually leading to male infertility. © 2015 American Society for Reproductive Medicine.
FAS-670 A/G and FAS-1377 G/A polymorphism in cell death pathway gene FAS and human male infertility
(Elsevier (Singapore) Pte Ltd, 2012) Deepika Jaiswal; Udai Shankar Dwivedi; Neeraj Kumar Agrawal; Sameer Trivedi; Kiran Singh
Objective: To study the role and association of functional variations present in FAS gene with idiopathic male infertility. Methods: The case-control study comprised of two groups: 160 idiopathic infertile nonobstructive azoospermia patients and 200 fertile healthy control men. Genotyping for single-nucleotide polymorphism of FAS-670 A/G (rs1800682) and FAS-1377 G/A (rs2234767) was done by PCR-RFLP method. DNA sequencing was used to ascertain PCR-RFLP results. For FAS-670 A/G and FAS-1377 G/A functional polymorphism, allele and genotype distribution were evaluated using Chi-square test. Results: Allele and genotype distribution did not differ significantly between patients and controls for FAS-670 A/G and FAS-1377 G/A. Conclusions: Human male infertility is a complex disorder and thus other genetic or environmental factors may be contributing to the complex etiology. © 2012 Hainan Medical College.
Gr/gr deletions on Y-chromosome correlate with male infertility: An original study, meta-analyses, and trial sequential analyses
(Nature Publishing Group, 2016) Sandeep Kumar Bansal; Deepika Jaiswal; Nishi Gupta; Kiran Singh; Rima Dada; Satya Narayan Sankhwar; Gopal Gupta; Singh Rajender
We analyzed the AZFc region of the Y-chromosome for complete (b2/b4) and distinct partial deletions (gr/gr, b1/b3, b2/b3) in 822 infertile and 225 proven fertile men. We observed complete AZFc deletions in 0.97% and partial deletions in 6.20% of the cases. Among partial deletions, the frequency of gr/gr deletions was the highest (5.84%). The comparison of partial deletion data between cases and controls suggested a significant association of the gr/gr deletions with infertility (P = 0.0004); however, the other partial deletions did not correlate with infertility. In cohort analysis, men with gr/gr deletions had a relatively poor sperm count (54.20 ± 57.45 million/ml) in comparison to those without deletions (72.49 ± 60.06), though the difference was not statistically significant (p = 0.071). Meta-analysis also suggested that gr/gr deletions are significantly associated with male infertility risk (OR = 1.821, 95% CI = 1.39-2.37, p = 0.000). We also performed trial sequential analyses that strengthened the evidence for an overall significant association of gr/gr deletions with the risk of male infertility. Another meta-analysis suggested a significant association of the gr/gr deletions with low sperm count. In conclusion, the gr/gr deletions show a strong correlation with male infertility risk and low sperm count, particularly in the Caucasian populations.
Human Male infertility: A Complex Multifactorial Phenotype
(2011) Kiran Singh; Deepika Jaiswal
Infertility is a major reproductive health problem affecting 10% to 15% of couples, with approximately equal contributions. Spermatogenesis is a dynamic and multistep process of male germ cell proliferation and differentiation by which spermatozoa are produced from primordial germ cells. The causes of spermatogenic defects in infertile men are multifactorial and many environmental, nutritional, behavioral and genetic factors affect male infertility. In most of the infertile cases, the underlying mechanisms remain obscure. Genomics and proteomics offer new tools for better understanding the genetics of male infertility. The current review provides insights into the plausible chromosomal, genetic and epigenetic alterations, which may result into infertile phenotype. © 2011, SAGE Publications. All rights reserved.
One-carbon metabolism, spermatogenesis, and male infertility
(2013) Kiran Singh; Deepika Jaiswal
Balanced diet is the natural source of micronutrients, such as folate and vitamins, vital for proper functioning of the body. One-carbon metabolic pathway along with folate and other vitamins plays an important role in DNA synthesis and in the establishment of epigenetic modifications like DNA/histone methylation. Spermatogenesis involves distinct cellular, genetic, and chromatin changes during the course of production of male gamete sperm. Folate and normal activity of 1-carbon metabolic pathway enzymes are central to nucleotide synthesis, methylation, and maintenance of genomic integrity as well as protection from DNA damage. As a result, polymorphisms in 1-carbon metabolic pathway genes affecting several physiological processes also have an impact on spermatogenesis and may affect directly or indirectly quality of sperm. Alterations in these processes may be a consequence of additive effect resulting from altered expression of 1-carbon metabolic pathway genes and/or inadequate folate/micronutrients supplementation. The present review provides an overview of different cellular and molecular events regulated by 1-carbon metabolic pathway enzymes and their impact on male reproductive health. It also summarizes the different studies where polymorphisms in the enzymes of 1-carbon metabolic pathway or folate deficiency are associated with male infertility and future prospects. © The Author(s) 2012.
Role of -460 C/T VEGF gene polymorphism in preeclampsia
(Elsevier (Singapore) Pte Ltd, 2013) Surbhi Roy; Manjari Matah; Deepika Jaiswal; Kiran Singh
Objective: To study association of VEGF-460C>T functional polymorphism with preeclampsia. Methods: The case-control study comprised of two groups: 40 pre-eclamsia patients and 45 healthy antenatal women. Genotyping for SNP-460 VEGF was done by ARMS-PCR method. For VEGF-460C>T functional polymorphism, allele and genotype distribution were evaluated using Chi-square test. Results: The prevalence of C allele was higher among cases compared to controls. The prevalence of CT and CC genotypes were also higher among cases compared to controls indicating that CT and CC genotypes and C allele to have a role in genetic susceptibility for preeclampsia. Conclusions: The carriage of VEGF-460C allele appears to be a risk factor for preeclampsia in present pilot study. © 2013 Hainan Medical College.