Repair genes expression of mouse cyclophosphamide chemotherapy in Repairing Sperm DNA Fragmentation inside Oocytes

Background and Aim: Sperm DNA fragmentation is one of the causes of male infertility. It is believed, oocyte can repair damages to the DNA of sperm after fertilization. Which factors may influence this capability of the oocyte? In this study, the ability of oocytes from mice treated with cyclophosphamide, in repairing sperm DNA fragmentation was evaluated Methods: Male and female FVB/N mice were used in this study. Modeling of DNA fragmentation in male mice spermatozoa was made by using of TBHP (Tert-Butyl hydroperoxide). TBHP dosage ranging determined from ۱۰۰ to ۶۰۰ mol/۱۰۰g on body weight. Obtain DNA fragmentation in adult mice sperm by injection of ۰.۱-۰.۲ LD۵۰ of TBHP were considered. Tert-butyl hydroperoxide was injected to ۶-۸ weeks adult male mice for two weeks. In order to create female mice model of chemotherapy, cyclophosphamide was injected at different doses and finally, after histological examination, ۶۰ mg/kg dose was selected. Two weeks after single dose administration and observation of the first estrous cycle, normal mating with male mice in the control (no drug) and TBHP-treated groups was performed. Finally, observing the post mating vaginal plaque and ۴ days after coupling, female mice were killed by cervical dislocation and blastocyst stage embryos. Gene expression of Rad۵۱, Brca۱, Mre۱۱a and Xrcc۴ was evaluated.Results: Data from the study of DNA repair double-strand break genes showed increased expression in the zygote embryonic stage when sperm and oocytes were damaged, whereas in the blastocyst stage we observed decreased expression of the mentioned genes.Conclusion: Maternal transcriptome storage in the oocyte can be effective for early repair of embryo damage to advance the embryo developmental stages. As embryonic development continues, embryonic genes are expected to be activated, nevertheless if the oocyte or sperm have been damaged, expression of these repair genes may be impaired or stopped.

Keywords:

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