This observation argues against the hypothesis put forward by Profet that menstruation is a mechanism for pathogen defense. The induction of menstruation in a species that does not normally menstruate and in the absence of any modification of the number of sexual contacts refutes the assumption that the copiousness of menstruation increases with the promiscuity of the mating system. Rather, our data indicate that it is a matter of costs and benefits: where there are large quantities of decidualized endometrial tissue, as was found in the mice in this study, it seems to be metabolically more economical to repel tissue rather than to absorb it. Taking both into account – the morphological uterine changes demonstrated here and the variations in hormone levels – we propose a functional correlation between overtly menstruating mice and human menstruation as shown in Figure 6. The proestrus in mice might represent the proliferative phase in women, since estrogen is the dominant hormone at this time. After induction of vitexicarpin pseudopregnancy, however, progesterone levels are greatly increased, indicating the similarities to the human secretory phase. The bleeding between day 7 and day 10 which is triggered by the drop in progesterone mimics menses, and day 12 corresponds to tissue repair in the early proliferative phase. Indeed, similar regulation of marker genes also supports the proposed link between overtly bleeding mice and human menstruation. Fn1 mRNA was increased in the ‘‘secretory-like’’ phase on day 4 of pseudopregnancy in line with human progestin-stimulated FN1 expression. Increased expression of stromal cell-derived vimentin during the human secretory phase and on day 4 of mouse pseudopregnancy might account for the cyclic variations in tissue composition in both species. The significant down-regulation and subsequent up-regulation of the epithelium-derived keratin 19 mRNA is thought to be a molecular sign of ongoing epithelial breakdown and repair as suggested by immunohistological investigations. In addition, the expression of Pecam1 was increased during bleeding in mice, and PECAM1 is intensely stained in stroma and endothelial cells during human menstruation. Correspondingly, the mRNA of the pro-angiogenic factor VEGF-A,Praeruptorin-B which is highly up-regulated in human menstruation, reached its highest level of expression during bleeding in mice. The growth activity of stroma cells is elevated in both the proliferative phase and the late secretory phase of the menstrual cycle, whereby the latter is induced by progesterone in a second wave of proliferation. By investigating the expression of Mki-67 mRNA which is expressed by cycling cells, we demonstrated progesteroneinduced proliferation on day 4 of pseudopregnancy in mice. Moreover, humans display cyclic mRNA expression of the prosurvival factor BCL-2. A contribution of apoptosis was likewise demonstrated in menstruation-like processes in mice. The Bcl2/Bax ratio was exclusively decreased during bleeding as an indicator of the regulation of survival and apoptosis. Whether Hmox1 displays cycle-dependent expression during human menstruation is not completely understood. However, Hmox1 mRNA is typically induced after erythrocyte lysis and in hypoxia and inflammation, suggesting increased expression during tissue breakdown and bleeding which was confirmed by our data. Menstrual breakdown is triggered by prostaglandins, and both rate-limiting enzymes of prostaglandin synthesis, PTGS1 and PTGS2, display cyclic expression. The high expression of PTGS1 on day 4 of pseudopregnancy and increased expression of PTGS2 during bleeding are consistent with human data. It is widely accepted that immunological mediators play a role in menstruation and, correspondingly, we detected regulated gene expression for pro-inflammatory cytokines like Il6 and Il15, as has been described in humans.