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International Journal of Fertility and Sterility، جلد ۷، شماره ۳، صفحات ۱۷-۱۷
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عنوان انگلیسی I-37: Genome Instability and DNA Damage in Male Somatic and Germ Cells Expressed as Chromosomal Microdeletion and Aneuploidy Is A Major Cause of Male Infertility
چکیده انگلیسی مقاله Background: Sperm chromatin insufficiencies leading to low sperm count and quality, infertility and transmission of chromosomal microdeletion and aneuploidies to next generations can be due to exposure to environmental pollutions, chemicals and natural or manmade ionizing radiation. In this project which has continued for more than 10 years and is unique in many technical aspects in Iran and in the region, genome instability induced by exogenous DNA damaging agents in sperm or spermatogenic cycle, the correlation of DNA damage with chromosomal microdeletion and aneuploidy, sperm chromatin alterations in failed fertilized oocyte's, chromosomal alterations in preimplantation embryos and localization of DAZ microdeletion on sperm nuclei were studied. Correlation of DNA damage induced during spermatogenesis leading to chromosomal aneuploidy and micronuclei in mouse preimplantation embryo is shown. Materials and Methods: To do these, various cytogenetic methods such as metaphase analysis, micronucleus assay, sperm chromosome study using Golden hamster zona free oocytes, fluorescent in situ hybridization (FISH) and primed in situ labeling (PRINS) was used. Sperm DNA damage was assessed using the alkaline comet assay and CA3 staining. Impact of DNA damage and chromosomal abnormality in sperm on in vitro fertilization and pregnancy outcome is also studied. Real time PCR was performed for three markers (SY 1206, SY 1197, SY 579) for testing copy number variation before and after irradiation. For evaluation of DAZ gene on Y chromosome in sperm nuclei a combined Primed in situ labeling (PRINS) and fluorescence in situ hybridization (FISH) technique was used for the first time. Results: Results indicate that sperm DNA damage in fertile and subfertile patients increased with increasing severity of male infertility and is well correlated with chromosomal aneuploidy especially sex chromosomes. Copy number variations of studied markers in AZFc region (microdeletion and duplication) after exposure to radiation increased with a dose dependent fashion (p< 0.001). Correlation of DNA damage and chromosomal aneuploidy with in vitro fertilization and pregnancy outcome is also shown. Using FISH-PRINS technique showed that DAZ microdeletion on sperm nuclei can be easily evaluated and shown that situation of DAZ microdeletion in somatic and germ cells might not be always similar. Conclusion: A direct correlation between protamine deficiency and sperm DNA damage was found for all subfertile patients studied and also sperm DNA damage is well correlated with chromosomal aneuploidy especially sex chromosomes. DNA damage might be involved in the process of malsegregation of chromosomes. This study indicates that genomic instability in infertile men could probably contribute to the development of an impaired reproductive capacity. Irradiation of gonads during spermatogenesis may lead to unstable chromosomal aberrations and probably stable chromosomal abnormalities affecting pairing and disjunction of chromosomes in successive preimplantation embryos expressed as MN. Increased frequency of induced microdeletion and duplication in infertile men compared with normal might be attributed to the deficiency in repair systems and the genetic factors involved in incomplete spermatogenesis of infertile men. Therefore, evaluation of DAZ microdeletion on sperms of male candidates for ICSI is necessary instead of simply using somatic cells for DAZ evaluation.
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نشانی اینترنتی http://ijfs.ir/journal/article/abstract/3418
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