Cyclophosphamide chemotherapy may reduce the repairing capacity of oocyte in confronting sperm dna fragmentation

سال انتشار: 1399
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 234

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شناسه ملی سند علمی:

BIOCONF21_0702

تاریخ نمایه سازی: 7 شهریور 1400

چکیده مقاله:

In recent years, sperm DNA fragmentation have been considered as a factor in the diagnosis of male infertility and assisted reproductive techniques(ART). It is believed that oocytes play a crucial role in repairing sperm DNA fragmentation after fertilization and in the embryonic stage. In this study, the ability of mouse Oocytes after chemotherapy to repair sperm DNA fragmentations was investigated. Animal models of DNA fragmentation creates by inducing oxidative stress in sperm and damage to oocytes was makde by chemotherapy drugagent, we aimed to investigate the role of oocytes in repairing fragmentation by examining the expression of DNA repair genes of Rad۵۱, Brca۱, Mre۱۱a and Xrcc۴ in the resulting embryos at two stages (Zygote and blastocyst).DNA breakage was induced in male FVB/N mice by injection of TBHP (Tert-Butyl hydroperoxide) that causes oxidative stress. Dosage of ۰.۱-۰.۲ LD۵۰ of TBHP were considered to induce DNA fragmentation in adult male mice (۶-۸ weeks of age) for two weeks. In modeling female mice with cyclophosphamide chemotherapy, after injection of different doses and histological survey of ovarian tissue and follicular count, dose ۶۰mg/kg of cyclophosphamide was selected. After a single dose injection of cyclophosphamide and two weeks recovery and the first estrous cycle observation, mating was performed between male and female mice in different groups. Finally, zygote and blastocyst collection was performed ۱۲ hours and ۴ days respectively after observing the vaginal plaque. The expression of double-stranded DNA breaks genes including Brca۱, Mre۱۱a, Xrcc۴ and Rad۵۱ was evaluated by Real time PCR. Data from the study of DNA repair double-strand break genes showed increased expression in the zygote embryos derived from mating of mice with DNA fragmented sperm and female mouse treated with chemotherapy agent, whereas in the blastocyst stage we observed decreased expression of the mentioned genes. Damaged sperm in the groups greatly increased the repair activity Whether the oocyte is healthy or damaged. The maternal transcriptome of oocytes seems to play an effective role in repairing sperm DNA fragmentation, but oocytes after chemotherapy may lose not only their capacity to repair damages to themselves but also damages to sperms.

کلیدواژه ها:

Oxidative stress‚ Reactive oxygen species‚ ROS ، Repair gene ، Cyclophosphamide

نویسندگان

Aysan Pourafshar dizaji

Department of Molecular Genetics, Faculty of Basic sciences and Advanced Technology, University of Science and Culture, Tehran, Iran

Hamid GOURABI

Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

Rouhollah Fathi

Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

Parvaneh Afsharian

Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran