Approximately 5 million American women suffer from endometriosis. It is the leading cause of infertility in industrialized nations and is the number one reason for hysterectomy prior to menopause. This often debilitating condition results from the growth of endometrial glands and stroma outside the uterus, which is most likely a consequence of the ectopic attachment of refluxed endometrial tissue. Survival of ectopic lesions requires evasion of immune surveillance, which normally acts to clear menstrual debris from the peritoneal cavity. Establishment of endometriosis further requires the invasive attachment of refluxed tissues and development of a vascular supply. In order to better understand the mechanisms of ectopic tissue attachment and vascular development, we have recently established experimental endometriosis in immunocompromised mice following adoptive transfer of human leukocytes. This new endometriosis model should be a valuable tool in which to examine the role of the immune system on multiple aspects of this disease. Studies outlined in Specific Aim 1 will further characterize the model, examining the migration patterns of human immune cells in RAG2?(c) mice with experimental endometriosis. The second series of studies within this aim will examine the impact of human immune cells from women with minimal/mild and moderate/severe endometriosis on establishment of experimental endometriosis in mice using autologous endometrial tissues.
In Specific Aim 2, we will specifically examine the impact of immune cells from women with endometriosis by obtaining immune cells from a woman with endometriosis and establishing experimental disease using endometrial tissue from a normal donor. These allogeneic recombination studies should provide important insight into the role of the immune system in endometriosis.
In Specific Aim 3, we will examine leukocytes within experimental lesions that are responsive to therapeutic regression with progesterone (established by normal endometrium) versus tissues that are resistant to progesterone (established with endometrium from women with endometriosis).Similar studies will be conducted using the allogeneic tissue and cell recombinations. Development of this model system should provide important insight into determining the role of immune cells during establishment, progression and regression of endometriosis. With this information, better treatment strategies that target immune cell factors could begin to be developed. ? ? ?
| Herington, Jennifer L; Crispens, Marta A; Carvalho-Macedo, Alessandra C et al. (2011) Development and prevention of postsurgical adhesions in a chimeric mouse model of experimental endometriosis. Fertil Steril 95:1295-301.e1 |
| Bruner-Tran, Kaylon L; Carvalho-Macedo, Alessandra C; Duleba, Antoni J et al. (2010) Experimental endometriosis in immunocompromised mice after adoptive transfer of human leukocytes. Fertil Steril 93:2519-24 |
