Investigation of the role of sirtuin 1 in embryo implantation in mice paraquat induced oxidative stress

Objective: Implantation is process of embryo placement in maternal uterus. Synchronization of development of zygote to blastocyst and uterus becomes receptive are critical. Sirtuins are highly conserved histone/protein deacetylases. Sirtuin1 is involved in processes such as resistance to oxidative stress, apoptosis, aging and inflammation. Sirtuin1 performs these functions by deacetylating transcription factors such as FoxO. Paraquat is an oxidative stress generating agent. We aimed to determine amount of Sirtuin1, FoxO1 and antioxidant MnSOD regulated by FoxO1 in pregnant mice treated with paraquat and Sirtuin1 activator SRT1720. Method: On 5th day of pregnancy, control, vehicle, paraquat, SRT1720 and SRT1720+paraquat groups formed by Balb/C mice were as follows: control group with no injection; vehicle group SRT1720 and paraquat solvents injected on days 1-4 of pregnancy; paraquat group injected with 30 mg/kg of paraquat 4th day of pregnancy, SRT1720 group injected with 50 mg/kg SRT1720 on days 1-4 of pregnancy; SRT1720+paraquat group injected with 50 mg/kg SRT1720 on days 1-4 of pregnancy and 30 mg/kg paraquat on 4th day of pregnancy. Mice in all groups were sacrificed after Chicago blue injection on day 5 morning of pregnancy, implantation and inter-implantation sites, uteri were taken. FoxO1 and Sirtuin1 were detected with immunohistochemistry and Western blot; acetylated lysine were detected with Western blot; ROS/RNS and MnSOD were detected with ELISA. Results: Sirtuin1 showed nuclear, FoxO1 showed both nuclear and cytoplasmic expression. There was no implantation in paraquat group. Sirtuin1 and FoxO1 expressions were increased in SRT1720 treated groups. As a result of FoxO1 deacetylation due to Sirtuin1 activation in SRT1720 treated groups, increased MnSOD caused ROT/RNT decrease. Conclusion: In some of mice treated with paraquat and SRT1720, embryos implanted with increase of MnSOD by eliminating ROT/RNT. However, number of implanted mice and number of implantation sites were significantly lower than control, suggesting that SRT1720 concentration was insufficient. Anahtar Kelimeler: İmplantasyon, Oksidatif stres, Sirtuin 1, FoxO1, MnSOD