Quantitative cellular and molecular analysis of the effect of progesterone withdrawal in a murine model of...

The endometrium is a dynamic tissue that undergoes periodic growth, remodeling and breakdown under the influence of ovarian steroid hormones. To investigate the molecular mechanisms underlying these processes, we used a murine model to mimic the decidualization and regression observed in humans. Ovariectomized mice were treated sequentially with steroid hormones, and subsequently, to induce decidualization, oil was injected into the uterine lumen. The animals were then divided into progesterone-maintained and progesterone-withdrawal groups. In the latter group, a process similar to menstruation was induced. The uterine tissues were collected at several time-points after the induction of decidualization. Histological analysis demonstrated that decidualization and tissue degeneration were successfully induced with similar features to those observed during the human menstrual cycle. Immunohistochemical, morphometric, and microarray-based techniques were used to study the cellular and molecular changes. The volume fractions of leukocytes, macrophages, and neutrophils, but not endothelial cells, increased in decidualized uteri and decreased after major tissue degradation was completed. The microarray data show that the levels of many transcripts that encode immune-related factors changed during the time-course used for this model, and the transcript levels of many of these factors paralleled the changes observed in the volume fractions of the immune cells. The results of the present study suggest that this model is a useful alternative to the use of non-human primates. Our findings also show that immune cells are recruited into the menstruating endometrium, and that immune-related genes are regulated in the uterus throughout menstruation.