association study between longitudinal changes of leukocyte telomere and the risk of azoospermia in a population of iranian infertile men

Background: Telomeres are evolutionary, specialized terminal structures at the ends of eukaryotic chromosomes containing TTAGGG repeats in human. Several human diseases have been known to be associated with dramatic changes in telomere length. The aim of the present study was to assess the correlation between the relative leukocyte telomere length [LTL] and infertility in a group of Iranian azoospermic males

Methods: In this casecontrol pilot study, relative telomere length [RTL] of peripheral blood leukocytes from a total of 30 idiopathic nonobstructive azoospermic males and 30 healthy fertile males was evaluated using real-time PCR. RTL was calculated as T [telomere]/S [single copy gene] ratio and compared between infertile and fertile groups

Results: Patients with azoospermia showed significantly shorter RTL than fertile males [0.54 vs. 0.84, p < 0.05]. The area under the receiver operating characteristic [ROC] curve was estimated to be 99.8%, suggesting LTL as a potential marker for the diagnosis of azoospermia

Conclusion: Our findings demonstrated a probable association between telomere shortening and azoospermia in a population of Iranian infertile men affected by idiopathic azoospermia

Premature ovarian failure: a critical condition in the reproductive potential with various genetic causes

Premature ovarian failure [POF] is identified as a heterogeneous disorder leading to amenorrhea and ovarian failure before the age of 40 years. The first known symptom of the disease is having irregular menstrual periods. The phenotype appearance of POF depends significantly on the variations in hormones. Low levels of gonadal hormones [estrogens and inhibins] and increased level of gonadotropins [luteinizing hormone [LH] and Follicle stimulating hormone [FSH]] [hypergonadotropic amenorrhea] are well documented as causes of POF. There is an association between the failure of germ cell development and complete ovarian failure, and consistently decreased number of germ cells is more likely associated with partial ovarian failure resulting in secondary amenorrhea. A literature review on recent findings about POF and its association with genomic alterations in terms of genes and chromosomes. POF is a complex heterogeneous disorder. Some of POF cases are carriers of a single gene mutation inherited in an autosomal or X-linked manner while a number of patients suffer from a chromosome abnormality like Turner syndrome in mosaic form and manifest secondary amenorrhea associated with ovarian dysgenesis. Among many of the known involved genes in POF development, several are prove to be positively associated to the disease development in different populations. While there is a promising association between X chromosome anomalies and specific gene mutations with POF, genome-wide analysis could prove a powerful tool for identifying the most important candidate genes that influence POF manifestation

Phenylketonuria from genetics to clinics: an Iranian prospect

Phenylketonuria [PKU] is the most common autosomal recessive disorder of amino acid metabolism. The disease is caused mainly by mutations in the phenylalanine hydroxylase [PAH] gene, encoding phenylalanine hydroxylase [PAH] enzyme. The PAH enzyme deficiency results in the elevation of phenylalanine in the blood, which may cause severe irreversible mental retardation in the affected individuals. More than 500 different disease causing mutations have been identified in the PAH gene. Direct and indirect molecular approaches have been developed for carrier detection and prenatal diagnosis of PKU disease. Population distribution of the PAH gene mutations and the PKU disease varies in different countries. In view of relatively high prevalence of the disease in Iranian population, investigations toward the elucidation of molecular aspects of the disease were required. In the present article, clinical and molecular basis of the PKU disease, with emphasis on the studies performed in Iranian population, were reviewed

[Haplotype analysis of PvuII[a]-MspI-VNTR markers in PAH gene in Isfehan population]

In this study, PvuII[a], Mspi and variable number of tandem repeat [VNTR] markers at the phenylalanine hydroxylase [PAH] gene region were genotyped in 100 unrelated individuals and 20 families from Iranian population. The allele frequency, observed heterozygosity and frequency of PvuII[a]-MspI-VNTR haplotype was estimated, Among the estimated haplotypes by use of FBAT program, eight haplotypes were introduced as informative haplotypes at the PAH gene region in the population studied, which could be used in carrier detection of phenylketonurai [PKU]

New methods for Cancer treatment by targeting Aoptosis pathway

Apoptosis or programmed cell death is a process which occurs in the cell as a result of stress, damage, or crowding, or when the cell is no longer needed. During this process, the DNA is broken up and the entire cell is consumed by phagocytes around the body. Understanding of the apoptosis mechanism has provided a basis for novel targeted therapies that can induce death in cancer cells or sensitize them to established cytotoxic agents and radiation therapy. Regulation of apoptosis by molecules that effect functional proteins of apoptosis is one of the new ways for cancer therapy through inhibition of tumor growth. New research for cancer treatment by novel agents include those targeting the extrinsic pathway such as tumor necrosis factor-related apoptosis-inducing ligand receptor 1, and those targeting the intrinsic Bcl-2 family pathway such as Antimycin A [antisense Bcl-2 oligonucleotide] have shown interesting results of some cancers inhibition and treatment. This review will discuss current knowledge about the pathways and new treatments that target them

Signal transduction for cancer treatment

Signal transduction pathway was known as transmission process of molecular signals from extracellular surface to cytosol. A few signal transduction pathways are hyper- activated in cancer cells due to mutations in oncogenes and tumor suppressor genes that finally are led to block differentiation, excessive proliferation and apoptosis inhibition. In the last several years, there were major progress towards understanding of the molecular mechanisms of signal transduction pathways and cancer that have been led to design and development of drugs for cancer treatment by inhibiting these pathways. In contrast to chemotherapy and radiotherapy, signal transduction therapy was very selective and less toxic, and it's to be hoped that early chemotherapy and radiotherapy would be removed by signal transduction therapy in cancer treatment