NFKB1 rs28362491 and pre-miRNA-146a rs2910164 SNPs on E-Cadherin expression in case of idiopathic oligospermia: A case-control study

Abstract

Background:A notable proportion of idiopathic male infertility cases is accompanied by oligozoospermia; and yet, the molecular mechanisms of fertilization problem underlying this defect are still unclear. Epithelial cadherin has been involved in several calcium-dependent cell-to-cell adhesion events; however, its participation in gamete interaction has also not been fully investigated.Objective:The aim was to investigate the changes in the expression of E-cadherin, based on the frequency of Single nucleotide polymorphisms in Nuclear Factor Kappa-B 1 and pre-mir-146a in oligospermic men.Materials and Methods: In this case-control study, semen and blood samples of 131 oligospermic men as the case group and 239 fertile healthy men as the control group were analyzed. Variants single nucleotide polymorphisms rs28362491 and rs2910164 were performed using polymerase chain reaction-restriction fragment length polymorphism method and E-cadherin expression were determined by immunoprecipitation studies.Results:ins/ins genotype of rs28362491 was determined as a risk factor for idiopathic oligospermia by 1.73 times (p=0.0218), whereas no significant differences were found between the groups concerning pre-mir-146a rs2910164 polymorphism (p=0.2274 in case of GC genotype and p=0.9052 in case of GG genotype). Combined genotype analysis results did not show any notable differences between the multiple comparisons of 28362491-rs2910164 in oligospermic men and control groups. In addition, E-cadherin expression of oligospermic men with ins/ins genotype was significantly lower than patients with del/ins genotype (p=0.0221). E-cadherin expression level was low in oligospermic men with respect to the control group in presence of ins/ins genotype of NFKB1 gene.Conclusion:These results suggest that ins allele prevents binding of surface proteins to spermatozoa, leading to a low affinity of sperm-oocyte interaction in oligospermic men.

Functional variations of NFKB1 and NFKB1A in inflammatory disorders and their implication for therapeutic approaches

“…We found increased risk of development of male infertility associated with the presence of the ins allele of NFKB1. Moreover, in the context of low E-cadherin expression, NFKB1 rs28362491 ins/ins and del/del genotypes are likely to display an essential role in the case of susceptibility to oligospermic male infertility [55]. In other works, we were not able to find any correlation of rs28362491 within NFKB1 or the rs696 polymorphisms within NFKB1A in cases of elevated apoptosis in oligospermia.…”

Sperm Antioxidant Biomarkers and Their Correlation with Clinical Condition and Lifestyle with Regard to Male Reproductive Potential

“…50%), while about 20% of infertility cases involve overlapping male and female factors. Idiopathic infertility remains to be a major problem in all cases of not-recognized male infertility [ 5 , 11 ].…”