Identification of new mutations in mitochondrial ATPase6 and ATPase8 genes in asthenospermic infertile men and investigation of protein structure using molecular dynamics simulation

سال انتشار: 1398
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 362

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شناسه ملی سند علمی:

RMED08_140

تاریخ نمایه سازی: 21 مرداد 1398

چکیده مقاله:

Background: Infertility affects 10% and 15% of couples, accounting for about 50% of infertility related to male factor. Approximately 30% of male infertility factors are associated with genetic disorders such as a mutation in nuclear genes and mitochondria. Mitochondria in various forms affect infertility. The ability to move active flagella is important for the proper functioning of the sperm and the successful transmission of the female reproductive system. The mitochondria supply the energy of sperm through the oxidative phosphorylation through the electron transfer chain. However, mitochondria in the middle segment of sperm as the major source of intracellular reactive oxygen species and free radicals, leading to lipid peroxidation and the formation of reactive products such as malondialdehyde and ultimately leads to a reduction in fertility in men.Objective: The aim of this study was to determine the genetic evaluation of mitochondrial ATPase6 and ATPase8 regions in asthenospermic infertile men and the association between mutations in these region with two biochemical markers of oxidative stress and to investigate the effect of known mutations on the structure of proteins encoded by these two genes for better understand the performance of these two protein subunits. Materials and Methods: In this study, 100 samples of semen from the fertile and infertile men of asthenospermia from Infertility Center of Shahid Beheshti Hospital in Kashan were collected. The sperm cells were isolated from the semen by the swim up. The total antioxidant capacity and malondialdehyde plasma levels of the seminal were measured. After extraction of DNA from the semen, the mtATPase6 and ATpase8 region was amplified by PCR technique. By determining the sequence of this region in the patient samples, 43 nucleotide changes were reported. Then, using the PANTHER and polyphen-2 database, the effects of mutations were investigated. After modeling the desired protein, molecular dynamics simulation of two malignant mutations was performed to investigate the effect of structural changes in the protein.Results: Our results showed that the average level of ATC of semen plasma in infertile men was significantly lower than that of fertile men, compared with malondialdehyde level of infertile men was significantly higher than fertile men. These results indicate a low sperm motility relation with electron transfer impairment, while simulation results indicate structural changes in proteins.Conclusion: Therefore, clarifying the molecular basis of these defects in infertile men with asthenospermia with a history of unknown infertility is necessary for better diagnosis and management of infertility treatment.

نویسندگان

Z Zare-Dehghanani

Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran