CITATION: Kikuchi-Arai M, Murakami T, Utsunomiya H, Akahira J, Suzuki-Kakisaka H, Terada Y, Tachibana M, Hayasaka S, Ugajin T, Yaegashi N. Establishment of long-term model throughout regular menstrual cycles in immunodeficient mice. Am J Reprod Immunol 2010 PROBLEM: The number of uterus natural killer (NK) cells change through the menstrual cycle, but the origin of uterus NK cell was not unclear. Our aims are to study whether we can reproduce repetition of menstrual cycle and to reveal the origin of uterus NK cells. METHOD OF STUDY: Endometrial samples were obtained from fertile women, and the tissues were transplanted into ovariectomized non-obese diabetic (NOD)/severe combined immunodeficiency (SCID)/γCnull (NOG) mice. Mice were treated with sex hormones which were in accord with human menstrual cycle. RESULTS: The replants showed similar histological changes as in eutopic endometrium repeatedly. CD56-positive, CD16-negative NK cells increased significantly during the treatment with estradiol and progesterone combination. CONCLUSION: Histological assessment demonstrated that this model of NOG mice repeatedly exhibited regular menstrual cycles, and this model mimicked not ‘ectopic endometrium’, but ‘eutopic endometrium’ in humans. Change in number of NK cells suggested that NK cell might be derived from the endometrium.