This triggers the breakdown of endometrial tissue and the flushing of shed endometrium and blood in human overt menstruation, or the reabsorption of the endometrial lining in the estrous cycle. Consequently, common laboratory animals such as mice or rats cannot be used to directly study the mechanisms of overt menstruation as it occurs in humans. In this regard, Finn and Pope described in 1984 a mouse model that mimics menstruationlike processes: ovariectomized mice treated with a special hormone schedule showed decidualization after intrauterine oil injection, endometrial breakdown after progesterone withdrawal, and repair thereafter. However, it has to be considered that utilizing ovariectomized mice combined with an artificial hormone supply excludes any natural impact of ovarian hormones, estrogen and progesterone, which are essential to govern the endometrial functions in human menstruation. Surprisingly, even though the intrinsic drawbacks of this model have been well recognized, very little work has been done to develop it further. In recent studies, the artificial exogenous hormone supply was still necessary and visible bleeding and shed tissue comparable to that seen in women has never been observed in mice. There is therefore still a great need for a model that mimics human menstruation. Against this background it first has to be clarified Procyanidin-B1 why certain species repel rather than reabsorb endometrial tissue and which mechanisms turn a non-menstruating species into an overtly menstruating species. Among other theories, menstruation has been proposed as a mechanism to protect the uterus from sperm-borne pathogens. Another hypothesis suggests that repelling or reabsorbing the endometrial lining might be less costly than keeping it in an active metabolic state by luteal maintenance. Whether expulsion or absorption takes place might be determined by the amounts of tissue and blood: for large quantities of blood and tissue shedding and flushing might be more economical. To prove whether overt bleeding is determined by the quantity of differentiated endometrial tissue, or whether it is restricted to Procyanidin-B2 a few species the feasibility of inducing overt bleeding in mice was tested. Intact pseudopregnant mice were used to exploit intrinsic hormonal changes largely comparable to the human situation. The transferability to human menstruation was verified by investigating bleeding intensity and endometrial gene expression and by histological examination of the uteri. Importantly, in mice with decidualized endometrium the spontaneous drop of endogenous progesterone levels was sufficient to induce menstruationlike processes including the extravaginally visible bleeding typically seen in overt menstruation. Moreover, within this time course the color of the uteri changed from pink to dark red and back to pink. Overall, decidualized endometrium of pseudopregnant mice displays immense morphological changes: tissue construction, breakdown, extravasation of blood, and repair, accompanied by gain and loss of uterine weight and size, and, most importantly, by overt vaginal bleeding. Coordination of the various menstrual events is achieved by regulation of a number of genes involved in processes such as decidualization, angiogenesis, proliferation, apoptosis, and inflammation. In order to discover how the menstruation-like bleeding seen in mice correlates with the endometrial expression of genes known to be regulated in human menstruation, we analyzed mRNA levels at different points in time as shown in Figure 5. Endometrial samples were collected from mice in proestrus, on day 4 of pseudopregnancy, and after decidualization on day 9 of pseudopregnancy and on day 14. In general, we identified three different mRNA expression profiles.