Reproduction of menstrual changes in transplanted human endometrial tissue in immunodeficient mice

• Published in: Human reproduction (Oxford) 2005-06, Vol.20 (6), p.1477-1484
• Main Authors: Matsuura-Sawada, Rui, Murakami, Takashi, Ozawa, Yuka, Nabeshima, Hiroshi, Akahira, Jun-ichi, Sato, Yumi, Koyanagi, Yoshio, Ito, Mamoru, Terada, Yukihiro, Okamura, Kunihiro
• Format: Article
• Language: English
• Subjects: Adult; Animals; Biological and medical sciences; CD3 Complex - metabolism; CD56 Antigen - metabolism; endometrial transplants; Endometrium - drug effects; Endometrium - metabolism; Endometrium - pathology; Endometrium - transplantation; Estradiol - pharmacology; Female; Gynecology. Andrology. Obstetrics; human endometrium; Humans; Immunocompromised Host; immunodeficient mouse model; Ki-67 Antigen - metabolism; Lymphocytes - metabolism; Medical sciences; menstrual cycle; Menstruation - physiology; Mice; Mice, Mutant Strains; Middle Aged; Progesterone - pharmacology; Receptors, IgG - metabolism; Tissue Transplantation - methods; Transplantation, Heterologous
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/deh783

BACKGROUND: Cultures of human endometrial tissue are useful for analysing the mechanisms underlying the menstrual cycle. However, long-term culture of endometrial tissue is difficult in vitro. Xenotransplantation of normal human endometrial tissue into immunodeficient mice could allow prolonged survival of the transplanted tissues. METHODS: Proliferative-phase endometrial tissue samples from three women were transplanted into the subcutaneous space of ovariectomized, immunodeficient, non-obese diabetic (NOD)/severe combined immunodeficiency (SCID)/γCnull (NOG) mice. The mice were treated with 17β-estradiol (E2) for the first 14 days after transplantation, followed by E2 plus progesterone for the next 14 days. The transplants were investigated morphologically and immunohistochemically at various times after implantation. RESULTS: The transplanted tissues contained large numbers of small glands, pseudostratification of the nuclei and dense stroma after treatment with E2 alone. After treatment with E2 plus progesterone, subnuclear vacuolation, luminal secretion and decidualization of the stroma were observed. When the hormone treatment ceased, tissue destruction occurred and the transplants returned to the proliferative phase. Lymphocytes were identified immunohistochemically: the numbers of CD56-positive and CD16-negative cells increased significantly in the stroma during the late secretory phase (day 28). CONCLUSIONS: Human endometrial tissue transplanted into NOG mice showed similar histological changes to eutopic endometrial tissue during treatment with sex steroid hormones for 1 month. Moreover, lymphocytes were produced in the transplanted human endometrial tissue. This system represents a new experimental model of the human endometrium in vivo.