Downregulation of miR-211 expression in the blood plasma of infertile men compared to the fertile controls.

OBJECTIVES: Infertility is inability to conceive after 12 months of regular unprotected sex. MiRNA expression changes can serve as potential biomarkers for infertility in males due to impaired spermatogenesis. This research was conducted to measure the expression level of miR-211 in plasma samples as a factor identifying infertility in comparison with the control group. METHODS: In this study, blood plasma were taken from the infertile men (n = 103) nonobstructive azoospermia (NOA) or severe oligozoospermia (SO) and the control group (n = 121). The expression of circulating miR-211 in plasma was assessed by qRT-PCR. A relative quantification strategy was adopted using the 2-ΔΔCT method to calculate the target miR-211 expression level in both study groups. RESULTS: Plasma miR-211 levels were significantly lower in infertile men compared to the control group (0.544 ± 0.028 and 1.203 ± 0.035, respectively, p < 0.001). Pearson's correlation analysis showed that miR-211 expression level has a positive and significant correlation with sperm parameters, including sperm concentration, sperm total motility, progressive motility, and normal morphology (p < 0.001). CONCLUSIONS: Decreased expression of miR-211 in blood plasma seems to be associated with male infertility. This experiment showed that miR-211 can be considered as a biomarker for evaluation, diagnosis, and confirmation of the results of semen analysis in male infertility.

Effect of smoking on methylation and semen parameters.

One type of epigenetic modification is genomic DNA methylation, which is induced by smoking, and both are associated with male infertility. In this study, the relationship between smoking and CHD5 gene methylation and semen parameters in infertile men was determined. After the MS-PCR of blood in 224 samples, 103 infertile patients (62 smokers and 41 non-smokers) and 121 fertile men, methylation level changes between groups and the effect of methylation and smoking on infertility and semen parameters in infertile men were determined. The results showed that there is a significant difference in the methylation status (MM, MU, UU) of the CHD5 gene between the patient and the control group, and this correlation also exists for the semen parameters (p < .001). The average semen parameters in smokers decreased significantly compared to non-smokers and sperm concentration was (32.21 ± 5.27 vs. 55.27 ± 3.38), respectively. MM methylation status was higher in smokers (22.5%) compared to non-smokers (14.6%). Smoking components affect the methylation pattern of CHD5 gene, and smokers had higher methylation levels and lower semen parameters than non-smokers, which can be biomarkers for evaluating semen quality and infertility risk factors. Understanding the epigenetic effects of smoking on male infertility can be very useful for predicting negative consequences of smoking and providing therapeutic solutions.

CHD5 gene (rs9434741) might be a genetic risk factor for infertility in non-obstructive azoospermia and severe oligozoospermia.

Inability to conceive is one of the health concerns. Chromodomain helicase DNA-binding protein5 (CHD5) gene is a major regulator in the replacement of histone proteins with protamines, the chromatin remodelling in spermatogenesis process. Thus, functional SNPs in this gene can disrupt sperm development. This study aimed to investigate the relationship between CHD5 polymorphism (rs9434741) and male infertility. This case-control study was conducted on 103 infertile and 121 fertile men. CHD5 polymorphism rs9434741 was tested using T-ARMS-PCR to investigate its association with male infertility. The presence of G allele caused 1.52 fold increase (OR = 1.52, 95% CI = 1.09-2.31 and p = 0.019) in infertility susceptibility in the patient group. GG genotype and (AG+GG) were significantly related to the increased risk of infertility (OR = 3.13, 95% CI = 1.26-7.76, p = 0.013; OR = 2.72, 95% CI = 1.35-5.47), respectively. Significant differences were observed between genotypes in NOA and SO groups compared to the control group (p = 0.029). Sperm count and total motility were significantly different among three genotypes in infertile men and the control group (p < 0.001). Analysis of genotypes and alleles frequency indicated statistically significant differences between the patient and control groups (p < 0.05). This study showed that CHD5 polymorphism (rs9434741) could be associated with the risk of male infertility. It is recommended to conduct further studies on different populations.

Analysis of the IL-10, IL-12, and TNF-α Gene Polymorphisms in Patients With Vesicoureteral Reflux Among the Southeast Iranian Population.

BACKGROUND: Vesicoureteral reflux (VUR) is a common childhood disorder that is characterized by the abnormal movement of urine from the bladder into the ureters or kidneys. OBJECTIVES: The aim of this study was to determine whether the genetic polymorphisms of the IL-10, IL-12, and TNF-α genes are involved in the development of VUR. PATIENTS AND METHODS: The tetra amplification mutation refractory system-polymerase chain reaction (Tetra-ARMS PCR) was applied to analyze the four polymorphic sites of the IL-10AG-1082, IL-10CA597, IL-12CA1188, and TNF308GA genes in 124 VUR children and 110 healthy controls. RESULTS: A significant, highly increased risk of VUR disease was found for the CA, AA, and combined genotypes of IL-10CA597 (OR = 5.2, 95% CL: 1.80 - 18.25; P = 0.0006, OR = 9.1, 95% CL: 1.11 - 122.75; P = 0.02, OR = 5.3, 95% CL: 1.82 - 18.61; P = 0.00052, respectively); the AG, GG, and AG + GG genotypes of IL-10AG-1082 (OR = 12.8, 95% CL; 2.9 - 113.9; P = 0.00003, OR = 12.62, 95% CL: 2.93 - 114.53; P = 0.00003, respectively); and the AA genotype of IL-12 (AA, OR = 0.19, 95% CL: 0.5 - 0.55; P = 0.0006). The frequency of the C allele in both IL-10CA and IL-12CA was greater in patients with VUR than in the healthy controls. No association was found between TNF308GA and the risk of VUR. CONCLUSIONS: The results demonstrated significant associations between the IL-10 (AG-1089, IL-10CA) and IL-12 (AA) gene polymorphisms and a highly increased risk of VUR.