These events are all conducive to the establishment, progression and survival of endometriotic implants within the peritoneal cavity. miR-451 has been validated to regulate post-transcriptional expression of proteins which, when over-expressed, may modulate these physiological events conducive to endometriotic implant establishment and/or survival such as macrophage migration inhibitory factor and 14-3-3 protein zeta . Based upon this information, coupled with the finding that miR-451 expression is reduced in eutopic endometrium from women with the disease, we postulated that this reduced expression in eutopic endometrium may enhance the ability of the endometrial tissue to establish ectopically. Alternatively, the reduced miR-451 expression in eutopic endometrium may be a result of the disease and not contribute to the establishment of the ectopic lesions. To answer these questions and determine if eutopic endometrial miR-451 plays a functional role in the establishment of ectopic endometrial lesions/endometriosis, we developed a mouse model for endometriosis which utilized mice which were deficient for miR-451 expression. The mechanisms by which endometriosis develops are poorly understood, but retrograde menstruation is proposed to play a role in the development of the disease. However, as almost all women exhibit some degree of reverse menses, there is strong belief that other contributing factors must exist. Considerable attention has focused on the alterations in eutopic endometrium from women with endometriosis which may make this tissue more likely to develop ectopically upon seeding into the peritoneal cavity during reverse menstruation. Based upon an initial report by Pan and colleagues which suggested that miR-451 expression in eutopic endometrium is significantly reduced compared to eutopic endometrium from women free of endometriosis, coupled with the belief that miR-451 regulates many factors which may play a role in the initial establishment of retrogradely shed endometrial fragments into endometriosis, we set out to determine if the level of eutopic endometrial tissue miR-451 expression influenced the ability of this tissue to establish ectopically. These observations may support the notion that reduced miR-451 expression in eutopic endometrium from women with endometriosis is a result of the disease, not a cause for its establishment as reduced expression within this eutopic tissue did not make it more apt to develop ectopically. In addition to the current study, this postulate is also supported by the observation that induction of endometriosis in baboons is associated with a reduction of eutopic endometrium miR-451 expression after the disease develops. Taken together, it appears that the reduced levels of miR-451 in eutopic endometrium of women with endometriosis do not functionally enhance the ability of this endometriotic tissue but lower in eutopic endometrium.