title: Induction of overt menstruation in intact mice.
abstract: The complex tissue remodeling process of menstruation is experienced by humans and some primates, whereas most placental mammals, including mice, go through an estrous cycle. How menstruation and the underlying mechanisms evolved is still unknown. Here we demonstrate that the process of menstruation is not just species-specific but also depends on factors which can be induced experimentally. In intact female mice endogenous progesterone levels were raised by the induction of pseudopregnancy. Following an intrauterine oil injection, the decidualization of the endometrium was reliably induced as a prerequisite for menstruation. The natural drop of endogenous progesterone led to spontaneous breakdown of endometrial tissue within an average of 3 days post induction of decidualization. Interestingly, morphological changes such as breakdown and repair of the endometrial layer occurred in parallel in the same uterine horn. Most importantly, endometrial breakdown was accompanied by vaginally visible (overt) bleeding and flushing out of shed tissue comparable to human menstruation. Real-time PCR data clearly showed temporal changes in the expression of multiple factors participating in inflammation, angiogenesis, tissue modulation, proliferation, and apoptosis, as has been described for human menstruating endometrium. In conclusion, human menstruation can be mimicked in terms of extravaginally visible bleeding, tissue remodeling, and gene regulation in naturally non-menstruating species such as intact female mice without the need for an exogenous hormone supply.
authors.affiliation: Target Discovery, Global Drug Discovery, Bayer HealthCare, Berlin, Germany. marion.rudolph@bayer.com
authors.forename: Marion
authors.initials: M
authors.lastname: Rudolph
authors.forename: Wolf-Dietrich
authors.initials: WD
authors.lastname: Döcke
authors.forename: Andrea
authors.initials: A
authors.lastname: Müller
authors.forename: Astrid
authors.initials: A
authors.lastname: Menning
authors.forename: Lars
authors.initials: L
authors.lastname: Röse
authors.forename: Thomas Matthias
authors.initials: TM
authors.lastname: Zollner
authors.forename: Isabella
authors.initials: I
authors.lastname: Gashaw
mesh_terms: D000818:Animals; D003656:Decidua / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D004717:Endometrium / Q000187:drug effects / Q000502:physiology; D030762:Estrous Cycle / Q000187:drug effects / Q000502:physiology; D004971:Estrus / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008600:Menstruation-Inducing Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015735:Mifepristone / Q000494:pharmacology*; D011374:Progesterone / Q000378:metabolism; D011555:Pseudopregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D008600:Menstruation-Inducing Agents; D012333:RNA, Messenger; D015735:Mifepristone; D011374:Progesterone