Bacterial endotoxin (LPS)-induced DNA damage in preimplanting embryonic and uterine cells inhibits implantation

Objective: To investigate lipopolysaccharide (LPS)-induced DNA damage in preimplanting embryonic and uterine cells during preimplantation period of pregnancy that may ultimately inhibit the process of implantation in mouse. Design: Animal study. Setting: Academic research environment. Animal(s): Sixty four Park strain female mice. Intervention(S): The minimum dose (MD) of LPS was injected intraperitoneally in the pregnant females oil day 0.5 of pregnancy, and individual embryos and uterine cells were assessed by comet assay on days 1.5, 2.5, 3.5, and 4.375 of the preimplantation period of pregnancy. Main Outcome Measure(s): Percentage of embryos and uterine cells with tail, mean comet tail length, percentage of fragmented DNA in tail. Result(s): Significantly higher numbers of embryos with higher mean comet tail length and percentage of fragmented DNA in tail were observed in the LPS-treated compared with control animals as the period of pregnancy approaches the stage of implantation. At the same time, DNA damage was also significantly higher in the uterine cells of LPS-treated compared with control animals. Conclusion(s): The MD of LPS can induce DNA damage in the preimplantation-stage embryos and uterine cells, which causes poor embryonic development and improper preparation of uterine horns during the preimplantation period of pregnancy, which may ultimately inhibit the process of implantation in mouse. (Fertil Steril (R) 2009; 91:2095-103. (C)2009 by American Society for Reproductive Medicine.)