S. M. Kalantar

Shahid Sadoughi University of Medical Sciences and Health Services, Yezd, Yazd, Iran

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Publications (9)6.32 Total impact

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    ABSTRACT: PURPOSE: To evaluate five common cystic fibrosis trans-membrane conductance regulator (CFTR) mutations (ΔF508, G542X, R117H, W1282X and N1303K) in the Iranian infertile men with noncongenital absence of vas deferens (CAVD) obstructive azoospermia. METHODS: The common CFTR gene mutations were tested on blood samples from 53 infertile men with non-CAVD obstructive azoospermia and 50 normal men as control individuals. Genomic DNA is extracted from the whole blood and the common CFTR mutations have been detected by the amplification refractory mutation system (ARMS) techniques. RESULTS: The common CFTR mutations were found positive in 5/53)9.43%(for ΔF508 and 4/53)7.55%(for G542X mutation of all patients tested. Also, no CFTR mutations were detected in the normal men. CONCLUSION: The common CFTR mutations were detected in 9/53(17%) infertile men with non-CAVD obstructive azoospermia. Pre-treatment CFTR mutation analysis remains critical to distinguish cystic fibrosis (CF) genotypes for men with non CAVD obstructive azoospermia.
    Journal of Assisted Reproduction and Genetics 10/2011; 28(11). DOI:10.1007/s10815-011-9632-7 · 1.72 Impact Factor

  • Iranian Journal of Reproductive Medicine 01/2011; 9, Suppl.1:23-24. · 0.19 Impact Factor
  • R. Mirfakhraie · M. Montazeri · S. M. Kalantar · N. Salsabili ·

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    ABSTRACT: Introduction: Pregnancy is the process from the fertilized ovum to the fetus with capability of extra uterine survival. Pregnancy loss is the most common complication of pregnancies. Advances in the detection of early pregnancy revealed that about 70% of human conceptions fail to achieve viability but clinically recognized pregnancies terminate as a miscarriage in about 15% of cases. About 1 in 300 couples and 0.5-2% of women are involved in repeated pregnancy loss (RPL). Various etiological factors involve in RPL and the main part of them remains unknown. The apoptotic changes and the aberrant expression of many genes including apoptotic related genes were seen in RPL. Material and methods: Familial pedigrees of 335 consecutive couples suffering from RPL were initially evaluated at a primary stage. Among them, 96 women were screened as idiopathic at reproductive age. Molecular genetic variations in internal apoptotic related genes BAX, BCL2 and mitochondrial genome were investigated in comparison to control group. The methods were PCR-SSCP, PCR-Digestion-SSCP, Multiplex PCR and PCR-Direct sequencing. Results: The evaluation of familial pedigree of 335 RPL couples showed 120 cases of RPL in female relatives and 76 cases in male relatives. Other families with RPL were seen in two or three consecutive generations in 15.6% of female relatives. At least two cases of RPL in other consanguineous marriages were observed in 4.2%. There were familial marriages in 51.6% of RPL women and 21.8% of control group (P=0.0003). A statistically significant association was observed between the study and the control groups with regard to the frequency of alleles A to G (97.76% in RPL and 90.71% in control group) at nucleotide -179 in Bax promoter region (P=0.013). G90C and G95A transitions were found in the coding region of exon 1 that change amino acid Glutamine (Q) to Histidine (H) and Arginine (R) to lysine (K) respectively. A statistically significant association was observed between H allele (p=0.0001) and K allele (P<0.0001) and the occurrence of RPL. Two nucleotide variations were seen in molecular analysis of Bcl2 gene. The G66C alteration in all RPL and normal women and A735G in 36.46% of RPL cases and 43.75% of control group (P=0.1449). No deletions but a high frequency of point mutations were found in RPL females; some 129 variations were observed in RPL. The mean of the D-loop mutations was 8.79 and 4.90 in RPL and control group respectively (ANOVA=0.0001). Among them, 22 mutations were significant in RPL group and the insertion of C in nucleotide 114 was novel. The G90C variation of BAX gene and the mean of mtDNA mutations were significant in second familial pattern consisted of familial marriages with RPL. Discussion: The high frequency of RPL in maternal pedigree implicates the maternal background of the disorder. On the other hand, there were higher rate of familial repeats of abortion, RPL repeats and consanguineous marriage in RPL pedigrees. Such evidences show the genetic background. However, pedigree analysis has critical role in the approach of RPL women. Our result indicates a supportive role of RPL for A(-179)G mutation in Bax gene, but two polymorphisms, G90C and G95A found in exon 1, provide a susceptible background for promoting miscarriages. The BAX exon variations lead to Q7H and R9K, rotation of N-terminal part of BAX protein and decrease protein stability. We believe that Bax gene has an important role in pregnancy loss. But, the Bcl2 alterations don’t reflect any association in RPL. The RPL women did not have any deletions in mitochondrial genome. Deletions can lead to the early apoptosis, elimination of the cells and fetal loss. Although, we did not find any deletions in RPL women, investigating this issue in the aborted fetus as well could provide further information. High rates of mutations in D-loop of mtDNA were observed in maternal blood, a fact that may have a direct or indirect role in inducing RPL. There were 7 significant point mutations consisting of T16126C, T16189C, C16223T, C16294T, T16311C, T16362C, and T16519C more frequent in RPL females compared to the controls. Among 89 point mutations that were only detected in RPL group, C114 insertion was novel. Also, 15 variations were significant in this group. These variations can have important roles in RPL, independently or as a part of haplogroups. An obvious role of inheritance and genetic background are detected by analysis of familial patterns. It seems more studies on these significant mutations can lead to the presentation of a diagnostic panel for RPL patients. Furthermore, preclinical abortions which are usually reported as infertile couples, and also failure of in vitro fertilization are our next targets for expanding this research to infertility.
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    ABSTRACT: Genetic factors contribute about 10 per cent of male infertility. Among these, genes in azoospermia factor (AZF) region including AZFa, AZFb, AZFc and AZFd on the long arm of Y chromosome are considered most important for spermatogenesis. Deletions in these regions are thought to be involved in some cases of male infertility associated with azoospermia or oligozoospermia. We studied the incidence of AZF deletions among Iranian infertile men with idiopathic non-obstructive azoospermia. A total of 100 Iranian azoospermic infertile men were selected for the molecular study of Y chromosome microdeletions. The presence of 13 sequence tagged site (STS) markers from AZF region was investigated using multiplex polymerase chain reaction (M-PCR). One hundred fertile men were also studied as control group. Twelve (12%) patients showed Y chromosome microdeletions and among these, deletion in AZFb region was the most frequent (66.67%) followed by AZFc (41.67%), AZFd (33.33%) and AZFa (8.33%), respectively. Because of relatively high incidence of Y chromosome microdeletions among Iranian azoospermic patients, molecular screening may be advised to infertile men before using assisted reproductive treatments.
    The Indian Journal of Medical Research 09/2010; 132(9):265-70. · 1.40 Impact Factor
  • F. Mirzajani · R. Mirfakhraie · S. M. Kalantar · N. Salsabili · M. Montazeri ·

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    ABSTRACT: Objectives: Pregnancy loss is the most common complication of pregnancy. About 1 in 300 couples involve with Repeated Pregnancy Loss (RPL) and the main part of them remains unknown. Apoptosis plays a role in early human development and embryonic loss.The aberrant expression of apoptotic related genes is seen in RPL. It seems internal apoptotic pathway and mitochondria as a main core of it, have important role in fertilization and proliferation of the cells. Mitochondrial DNA (mtDNA) is not transmitted through nuclear DNA (nDNA), and in most multicellular organisms, virtually all mitochondria are inherited from the mother's ovum, as it is unusual for sperm cells to contribute mitochondria when fertilizing ova. Bax is an important nuclear gene in mitochondrial pathway of apoptosis.The protein encoded by this gene belongs to the BCL2 protein family. This protein forms a heterodimer with BCL2, and functions as an apoptotic activator. We believe that the mitochondria, Bax and Bcl2 genes are good candidate for investigation of pregnancy loss. Materials and Methods: 335 consecutive cases were studied. Genetic counseling, clinical, paraclinical, and cytogenetic studies were done for each couple. We analyzed the familial pedigree of them and then screened the idiopathic cases. In total 96 females who were suffered from idiopathic RPL. 1-Four multiplex PCR are done on each sample for detection of mitochondrial deletions. 2-Mitochondrial Dloop part consisting of the hyper variable regions is analyzed by PCR-sequencing method. 3-Bax gene is evaluated by PCR-sequencing method for promoter region and all seven exons. 4-Bcl2 gene is evaluated by PCR-sequencing method for promoter region and PCR-SSCP for the exons. Results: 1-No mitochondrial deletions were found in 96 DNA samples. 2-Mononucleotide repeat (poly C) from 303 to 315 nucleotide positions (D310) exhibited a polymorphic length variation and mutations (C ins. in 37, CC ins. in 8, CCC ins. in 1, TCCC in 1, TCCCC in 1, and TCCCCC in 1 female) 3- D-loop region was evaluated by direct sequencing and we found 166 different variations in our study population. Among them, 95 variations were seen in RPL cases, 28 in control samples, and also 43 in both of them. 4-Change of A to G in promoter region of Bax gene was seen at nt. 55 in 93 females (96.87%). Conclusion: 1-Because of oxidative stress is one of the important causes of mtDNA deletions we suggest that this phenomenon seems is less involving in pregnancy loss. 2-Some of these nucleotide alterations might be involved in repeated pregnancy loss and could be included in a panel of molecular biomarkers for susceptibility in pregnancy loss and even failure of invitro fertilization. 3-A high rate of mutation in mitochondrial DNA in the D loop was found in samples from patients with RPL relative to healthy controls. 4-In seven SNPs that were found in case and control groups, we found significant difference between groups (P<0.05) (T16126C, T16189C, C16223T, C16294T, T16311C, T16362C, T16519C). From the RPL group mutations, 15 SNPs were significant and four mutations was novel (A503G, A335G, T217C, C114ins.) 5-We believe that mutation in Bax gene will lead to early apoptosis. 6 The results can be used in assessment of RPL and probability of interventional treatment for improving of fertilization in ART methods.

  • Reproductive biomedicine online 12/2008; 16. DOI:10.1016/S1472-6483(10)61417-4 · 3.02 Impact Factor
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Publication Stats

23 Citations
6.32 Total Impact Points


  • 2011
    • Shahid Sadoughi University of Medical Sciences and Health Services
      • Research and Clinical Center for Infertility
      Yezd, Yazd, Iran