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

FABP9 mutations are not detected in cases of infertility due to sperm morphological defects in Iranian men

Fatty acid binding proteins [FABPs] are members of the intracellular lipid binding protein [iLBPs] family and most of them show tissue specific expression. FABP9/PERF15 [Perforatorial15] is the male germ cell-specific fatty acid-binding protein. It was first identified as the major constituent of the murine sperm perforatorium and perinuclear theca. To date, investigations in mice have demonstrated that this protein has a role in the male reproductive system, especially in spermatogenesis. Also, it has been reported that FABP9 can protect sperm fatty acids from oxidative damage. Recently it was shown that it can affect sperm morphology in mice. Based on these findings, we designed a study to evaluate if mutations of this gene can affect sperm morphology in humans. In this case-control study, DNA was extracted from peripheral blood of 100 infertile males with normal sperm count but with a number of morphologically abnormal sperms in their semen that was above normal. Four exons and one intron of the FABP9 gene were amplified by polymerase chain reaction [PCR], re-sequenced and then analyzed for mutation detection. We did not detect any mutation in any area of the four exons, intron 3 and splice sites of FABP9 gene in any of the studied 100 samples. There was no mutation in the exonic regions and the poor sperm morphology. However, we didn't analyze the promoter, intron 1 and 2 to establish conclusions regarding the association of these genic regions and sperm dysmorphology

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

Association between vitamin D receptor gene BsmI polymorphism and bone mineral density in a population of 146 Iranian women

Osteoporosis is a bone disorder that reduces bone mineral density [BMD] and leads to bone fracture. In addition to different factors, gene polymorphisms have been revealed to be associated with osteoporosis. In this study, we investigated the association between the BsmI polymorphism of vitamin D receptor [VDR] gene [rs1544410] and BMD in a population of Iranian women. In this case control study, clinical risk factors for osteoporosis were obtained from the participants through a questionnaire for a case-control study. The World Health Organisation [WHO] criteria were applied for the diagnosis of the disease. Peripheral blood samples were obtained from 146 pre- and or postmenopausal Iranian women aged between 35 and 71 years [53.53 +/- 9.8]. The study population was classified for BMD into normal and osteoporotic groups, who matched for age, pregnancy status, menstrual condition, and body mass index [BMI]. The BMD of the lumbar spine [L1-4] and femoral neck was measured. Polymerase chain reaction restriction fragment length polymorphism [PCR-RFLP] was performed to detect and analyze the genotype. The frequencies of AA and GG were significantly different between the two groups [p value<0.05], with the first genotype being higher in the patients and the second being higher in the normal group. The GG genotype was significantly associated with increased BMD in the lumbar spine [p value<0.05] but non-significant in the femoral neck [p value>0.05]. BsmI polymorphism of VDR gene has a significant association with BMD in the lumbar spine and may have a minor effect on the proximal femur BMD in Iranian women

novel human lipid binding protein coding gene: PERF15, sequence and cloning

PERF15 is a testicular germ-cell specific fatty-acid binding protein [FABP] isolated from mammals, originally from rats. It encodes one of the most abundant proteins of rat spermatozoa localized in the perinuclear theca. Northern blot analysis has demonstrated that rat PERF15 mRNA is exclusively transcribed during meiosis and post-meiosis. In this study, we cloned and sequenced human PERF15 gene. According to the open reading frame of automated computational analysis of Homo sapiens similar to testis fatty acid binding protein nine, two specific Primers were designed to amplify human PERF15 gene. To confirm the identity of the amplified gene, PCR products of PERF15 were cloned into appropriate plasmid vectors followed by sequencing of the inserts. A unique band of -3kb was obtained after PCR amplification. Restriction enzyme digestion using PvuII confirmed that the fragment was related to PERF15. Gene alignment, direct sequencing and application of specific primers to the gene showed 100% similarity between this gene and the computational data by gel extraction of the -3 kb band. The human PERF15 gene contained four exons and three introns. Exons one, two, three and four, respectively, coded for 24, 57, 34 and 17 amino acids. The existing three introns were composed of 2113, 461, and 168 nucleotides. In spite of the homology between exonic regions and exon-intron boundaries of human PERF15 gene and that of animals, human PERF15 gene is different in size and sequence from corresponding introns in rat and murine PERF15