Male Infertility In Iranian Population Research Articles

Susceptibility to azoospermia by haplotype analysis of protamine 1 and protamine 2 variants

Infertility remains a major global problem, affecting 10–15% of couples worldwide, with half of the cases due to male factors. Protamines, found only in the testes, are essential for sperm chromatin condensation and paternal genome imprinting during spermatogenesis. Seventy testicular samples from infertile men were analyzed for the expression level of PRM1 and PRM2. 448 infertile males were additionally examined for PRM1 and PRM2 polymorphism. There was a significant association of rs2070923 polymorphism of PRM2 in both additive and recessive models (OR (95% CI) 1.32[0.92; 1.88, p = 0.023] and 2.26[1.12; 4.57, p = 0.017], respectively). The TT genotype of rs2070923 PRM2 was also correlated with lower gene expression of PRM2 in the infertile group (p = 0.03). Moreover, our result showed that the frequency of GTCT haplotype was higher than average in azoospermic patients (OR = 2.67; 95%CI = 1.17–2.53; p = 0.041) and that gene-gene interaction played a role in male infertility. The linkage disequilibrium plot showed that rs2301365 was strongly associated with rs2070923. For the first time, we reported a significant haplotype of PRM1 and PRM2 genes associated with male infertility in Iranian population. These results are likely to contribute to a better understanding of the causes of male infertility.

P–020 AZFc partial microdeletions of the Y chromosome is associated with severe oligozoospermia among Iranian men

Abstract Study question Are AZFc partial deletions correlated with severe oligozoospermia in Iranian men? Can we consider them as risk factors for infertility? Summary answer The frequency of total partial AZFc microdeletions was significantly higher in the oligozoospermia group compared to control group (8% vs. 3%, P = 0.028). What is known already Among many factors affecting male infertility, the second most common genetic factor is Y chromosome microdeletion. Some studies on partial AZFc microdeletions (especially on three major types; gr/gr, b1/b3 and b2/b3) have associated them with impaired spermatogenesis (azoospermia and oligozoospermia) in infertile men from different ethnicities. This finding is attributed to differences in alterations in pattern of DAZ/CDY1 copy numbers as spermatogenesis related genes. Study design, size, duration 200 oligozoospermic (sperm count <5 mil./mL) and 200 fertile men were included as case and control groups, respectively. Individuals with karyotype abnormalities, complete microdeletions in AZF regions, infections, hypogonadism, history of chemotherapy and radiation, cryptorchidism or history of orchiopexy were not included. The study was approved by the Royan Institute Ethics Committee. Written informed consents were obtained from each participant. Participants/materials, setting, methods Total DNA from peripheral blood was used to amplify six sequence-tagged sites (STS) markers through multiplex PCR to detect AZFc partial deletions according to previous studies. Patterns of deletion in DAZ and CDY1 copies were determined through PCR- RFLP. Main results and the role of chance The frequency of AZFc partial microdeletions was 8% in oligozoospermic men (16/200) which was significantly higher compared to 3% in control group (6/200) (P = 0.028). Hence, partial deletions may be considered as a risk factor for the male infertility in Iranian population. Also, gr/gr showed a higher frequency in oligozoospermic group (4%) compared to controls (1.5%) (P = 0.126). The combination of DAZ1/2+CDY1b was the most observed deletion pattern in 8 oligozoospermic men with gr/gr deletion (75%), while among 3 controls with gr/gr, DAZ3/4+CDY1a (2 out of 3) and DAZ3/4+CDY1b (1 out of 3) were detected. Therefore, DAZ1/2+CDY1b can be correlated to oligozoospermia. Limitations, reasons for caution In order to achieve stronger statistical results, a larger sample size is of more help. Wider implications of the findings: Risk of vertical transmission to male offspring and expansion in the size of deletions should be considered when providing ART services to infertile men. Genetic counseling is suggested in oligozoospermic men. Trial registration number -

Detection of Polymorphisms in MTHFD1 G1958A and Its Possible Association with Idiopathic Male Infertility.

The role of male infertility is important in human infertility pathology. Spermatogenesis is a complex developmental process which is regulated by a number of genes. Methylenetetrahydrofolate dehydrogenase1 (MTHFD1) is involved in the synthesis of purine, pyrimidine, and methionine. The aim of this study was to identify the MTHFD1, G1958A polymorphism and its association with idiopathic male infertility in Iranian population. This case-control study was conducted on 200 Iranian men, 100 cases with idiopathic infertility (experimental group) and 100 normal men (control group). The subjects were assessed for the MTHFD1 G1958A polymorphism, using the polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP). The chi-square test was used to determine the association between MTHFD1 G1958A polymorphism and male infertility, using SPSS software. P ? 0.05 was considered significant. Totally, the frequency of A allele and AA homozygous genotype was found 51% and 47.3% respectively, with 52.5% and 30% in the experimental group versus 42% and 21% in control group. There was a statistically significant correlation between the frequencies of A allele (95 % CI = 1.028- 2.265, OR = 1.526, p = 0.035) and AA homozygous (% CI = 0.995- 4.494, OR = 2.114, 95 p = 0.05) genotype with the MTHFD1 G1958A polymorphism (P ? 0.05). These results suggest that the polymorphism in MTHFD1 G1598A gene could be considered as an important genetic disorder associated with the etiology of male infertility.

Certain TSGA10 polymorphisms are not associated with male infertility in Iranian population

Testis specific protein 10 (TSGA10) is expressed in normal adult testis and has been suggested to be involved in the normal function of sperms. Tsga10 expression has a role in the protection of spermatozoa and enhancement of male fertility. This gene has a number of single nucleotide polymorphisms (SNPs). In the current study, we genotyped rs3811553, rs200902126 and rs17852533 in 156 fertile men, 150 oligospermic and 150 azoospermic men using PCR-RFLP method. The genotyping showed that all assessed individuals were homozygote for wild type allele of both rs3811553 and rs200902126. In the case of the rs17852533, although we found the three genotypes in the studied individuals, there was no significant difference in distribution of these genotypes between the study groups. The current study shows insignificance of these SNPs in male infertility. However, future studies in larger sample sizes are needed to reach conclusive results.

HSPA1L and HSPA1B gene polymorphisms and haplotypes are associated with idiopathic male infertility in Iranian population

ObjectiveMale infertility is a multifactorial disease resulting from the interaction between the genetic and environmental factors. Spermatogenic failure accounts for more than half of male infertility cases. Heat shock proteins (HSPs) are the molecular chaperones that are involved in different developmental stages of spermatogenesis. The current study was planned to investigate the role of HSPA1L rs2227956 and HSPA1B rs1061581 gene polymorphisms in idiopathic male infertility. Study DesignThis case-control study was conducted on 516 subjects consisted of 308 patients with idiopathic male infertility and 208 age matched-(±5) control subjects. HSPA1L rs2227956 and HSPA1B rs1061581 polymorphisms were genotyped by PCR-RFLP method. ResultsA significant association with male infertility was found for HSPA1L rs2227956 in genotypes (TT vs CT: OR = 2.049, 95% CI = 1.337–3.139, P = 0.001; TT vs CC: OR = 3.028, 95% CI = 1.100–8.332, P = 0.032). In the dominant genetic model, rs2227956C allele increased the risk of male infertility (OR = 2.049, 95% CI = 1.337–3.139, P = 0.001). Also, the results showed a significant association between the HSPA1B rs1061581GG genotype and male infertility (OR = 2.638, 95% CI: 1.001–4.486, P = 0.001). The rs1061581 G allele was a risk factor for male infertility (OR = 1.657, 95% CI = 1.278–2.148, P < 0.001). Haplotype analysis showed CG and TA (rs2227956/ rs1061581) haplotype affect the risk of male infertility (P < 0.001). ConclusionHSPA1L rs2227956 and HSPA1B rs1061581 gene polymorphisms are associated with susceptibility to idiopathic male infertility in Iranian population. Further studies in different ethnicity are necessary to confirm these results.

Study of association the single nucleotide polymorphisms (rs6631) in 3′-UTR CGA gene with male infertility in Iranian population

ObjectiveStudying the possible association between SNP (rs6631) residing in the miRNA-binding-site of spermatogenesis-related gene (CGA) with azoospermia male infertility in Iranian population was our purpose of this research. CGA has essential role in gonads function. SNP is located in the miRNA-binding site in 3′ untranslated region (3′-UTR) gene may lead to disruption of CGA and elevate the risk of male infertility. MethodsBlood samples were collected from different ethnicities and their DNA was extracted by using salting out method. Sixty-eight infertile men suffer from azoospermia and sixty-three fertile men were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) technique and some of them were sequenced randomly. Statistical analyses were performed to investigate the association between rs6631 and azoospermia. ResultsCGA-215AA genotype was significantly associated with azoospermia infertility. Logistic regression analysis of the genotype frequency between fertile and infertile men revealed significant difference (p < 0.05) in all models of inheritance except recessive model. The most genotype frequencies for T215A in our studied population was heterozygote genotype (T/A), it was same as the results in NCBI. hsa-miR-1302 and hsa-miR-557 bind to rs6631-A (mutant allele) more stably than rs6631-T, so CGA expression may be dysregulated. As a result, this SNP may elevate risk of male infertility. ConclusionOur results indicated that the mentioned polymorphism in CGA gene could be associated with azoospermia male infertility in Iran. Further studies are required to support the obtained result.

Investigation of GRTH gene single nucleotide polymorphism in association with male infertility in Iranian population

IntroductionGRTH gene is located on chromosome 11q24 and consists of 14 exons. GRTH codes for a protein product which is involved in testicular function and spermatogenesis. The absence of this gene can lead to gametogenesis arrest. The purpose of this study was to investigate the association of SNP IVS6+55G→T (rs551373) in DDX25/GRTH gene with male infertility. MethodsIn this case-control study, DNA samples were extracted from 180 men, including 90 fertile men and 90 infertile cases with azoospermia by Salting out method. PCR-RFLP was conducted to identify the SNP in DDX25/GRTH gene. ResultsAccording to statistical analyses carried out in SPSS and SNPstats online software, the SNP rs551373 is significantly associated with azoospermic cases studied. ConclusionThe results of our study suggest that positive association of rs551373 SNP probably reveals an important role in azoospermia male infertility. Further studies with larger sample size are required to support our findings. Investigation of association of this SNP with other types of non-obstructive male infertility is also suggested.

Association study of SPATA-16 polymorphism with male infertility in Iranian population

IntroductionIt is estimated that about 15% of couples are confronted with the inability to conceive after 1year of unprotected intercourse. Genetic and environmental factors are the most important reasons that affect male infertility. SPATA16 is encoded by a gene that maps to human chromosome 3q26. The c.848G>A mutation has been predicted to change an amino acid of a highly conserved residue (p.R283Q). In addition, the c.848G>A mutation affects the last nucleotide of exon 4, and may disrupt the 5′ splice site of intron 4. Our purpose was to study association of individuals with globozoospermia and teratozzospermia and SNP rs137853118 located in exon 4 of SPATA-16 gene. MethodsDNA samples of 130 infertile couples suffered from teratozoospermia, globozoospermia, and 110 control individuals were collected from Royan institute. SNP genotyping was performed by PCR-RFLP technique following sequencing exon 4 region of SPATA-16 gene. ResultsThe rs137853118 SNP showed no polymorphism in patients and controls according to sequencing and statistical analysis. ConclusionsSPATA16 studied SNP did not exist in Iranian population and has no significant relation with globozoospermia infertility, although further studies on more samples are demanded. Furthermore, the study of genetic parameters did not show genetic variation between case and control individuals.

Association of Two Polymorphisms in H2B.W Gene with Azoospermia and Severe Oligozoospermia in An Iranian Population.

During spermatogenesis, the H2B family, member W (H2B.W) gene, en- codes a testis specific histone that is co-localized with telomeric sequences and has the potential role to mediate the sperm-specific chromatin remodeling. Previously H2B.W genetic variants were reported to be involved in susceptibility to spermatogenesis im- pairment. In the present study, two single nucleotide polymorphisms (SNPs) in 5΄UTR and exon 1 of H2B.W gene were examined to investigate possible association of these polymorphisms with male infertility in Iranian population. This case control study was conducted in Royan institute during four-year period (2010-2013). Genetic alteration of two SNPs loci, -9C>T and 368A>G, in H2B.W gene were indicated in 92 infertile men who were divided into two main groups includ- ing azoospermia (n=46) and sever oligozoospermia (n=46), while there was 60 fertile men as control group. Azoosperima was also divided into three sub-groups including sertoli cell only syndrome (SCOS, n=21), complete maturation arrest (CMA, n=17) and hypo spermatogenesis (n=8) according to testicular biopsy. For analysis, polymerase chain reaction-restriction frag- ment length polymorphism (PCR-RFLP) technique was applied. The frequency of allele -9T was significantly higher in CMA group than in patients with SCOS (P<0.05). The haplotype TA (corresponding to simultaneous occur- rence of -9T and 368A) compared with haplotype CA (corresponding to simultaneous occurrence of -9C and 368A) in patients suffering from CMA significantly increased, compared with patients had SCOS (P<0.05). However, statistical studies indicated that in general, the distribution frequencies of -9C>T and 368A>G had no significant difference between the infertile groups and control (P=0.859 and P=0.812, respectively). This investigation showed that SNP -9C>T might be contribute to CMA in azoo- spermic patients and SNP 368A>G had no correlation with male infertility in Iranian population.