The first was characterized by a peak in endometrial mRNA expression on day 4 of pseudopregnancy. This was shown for the stromal cell-derived vimentin, fibronectin 1, insulin growth factor 1, the proliferation marker Mki67, and the prostaglandin-endoperoxide synthase 1. The second expression pattern had a typical maximum of expression on day 9; the day of heaviest visible bleeding. By this day significantly increased expression was detected for Pecam1, which accounts for a large proportion of intercellular junctions of endothelial cells, and for the growth factor Vegfa. In addition, prostaglandin-endoperoxide synthase 2 was up-regulated 10-fold during bleeding compared to day 4. To sum up, the results imply that genes important for various cell- and tissue-specific processes were differentially regulated within the decidualized endometrium of pseudopregnant mice. In general, three expression patterns were represented. The pattern most frequently detected here was the up-regulation of genes during bleeding on day 9. Experimentally induced overt menstruation has not been reported for any species so far. Mouse models mimicking menstruation are known,Madecassoside but overt bleeding has never been described. The data presented in this study show that menstruation is not just species-specific. It is more likely that previous experimental approaches have not fulfilled the prerequisites for overt menstruation. Our data confirmed that pseudopregnant mice with decidualized endometrium display endometrial tissue destruction and repair. Moreover, for the first time, active flushing of shed tissue and blood from the vagina as a feature of overt menstruation was observed in mice. Uterine bleeding was triggered by the natural drop of previously increased Sanggenone-D endogenous progesterone, which occurred between day 7 and day 8 or day 8 and day 9 of pseudopregnancy. This temporal variation may reflect the individuality of mice with respect to the degradation of their corpora lutea in the ovary. Withdrawal of endogenous progesterone coincided with the onset of bleeding. The causal relationship of both events was confirmed by experimental antagonizing endogenous progesterone signaling through mifepristone administration that apparently caused almost immediate bleeding. The induction of overt bleeding in a naturally non-menstruating species like the mouse support the hypothesis that the amount of tissue and blood determines whether expulsion or reabsorption takes place. It was possible to achieve differentiation of a large amount of tissue by increasing the stimulus for decidualization in the form of a 5-fold larger volume of oil than that used by other authors. This led to decidualization of both uterine horns, which further increased the amount of tissue and blood to be flushed out. In order to obtain overt bleeding, we profited from the intrinsic ovarian regulation of intact pseudopregnant female mice compared to ovariectomized mice supplied by exogenous hormones used in former studies. In comparison to the established model, we prolonged the duration of the processes underlying bleeding: changes in uterus size and morphology occurred very rapidly within hours after progesterone withdrawal in ovariectomized mice, whereas these processes took place over a few days in our study. This extension of time, together with the determination of heavy bleeding by scoring bleeding intensity, will increase the feasibility of analyzing the kinetics of bleeding or its intensity. Hence, overtly bleeding mice are expected to be valuable for studying the molecular pathways affecting menstrual disorders such as menorrhagia. Our data demonstrate that the conversion of non-menstruating mice to mice displaying overt bleeding as a characteristic of menstruation is feasible.