Current mouse models of menstruation are invasive, often requiring multiple injections and ovariectomy. The result of these models is a rapid and extensive breakdown of endometrial tissue. Our aim is to develop a minimally invasive mouse model of menstruation utilising the endometrial changes that occur in early murine pregnancy and subsequent miscarriage. We are in the early stages of model development and aim to compare outcomes with known affects in other menstrual models, while acknowledging the potential impact of trophoblast on endometrial breakdown and repair.
Female mice (C57/B6) were mated and housed until gestational day (GD) 4.5 (day of embryo implantation) or 5.5. Miscarriage was then induced using the progesterone antagonist mifepristone (2 mg/kg). Mice were monitored for signs of vaginal bleeding and then culled between 6 and 24 hours after the mifepristone injection. Breakdown, bleeding and repair of the endometrium were assessed.
Administration of mifepristone at GD 4.5 resulted in structural changes within the uterus, however no vaginal bleeding was observed. Decidual tissue was present at implantation sites both 6 and 12 hours post mifepristone. No decidual tissue was observed by 24 hours. By 6 hours, red blood cells were noted within the decidual tissues, these persisted in the endometrium to 24 hours. Vaginal bleeding was noted in mice treated with mifepristone at GD5.5; we are currently analysing the endometrial tissues in these animals.
We propose that menstrual-like endometrial breakdown and bleeding can be induced in mice by inducing early miscarriage. We postulate that this model will provide an invaluable method of investigating factors impacting endometrial breakdown and repair in a minimally invasive manner.