Quantitative Cellular and Molecular Analysis of the Effect of Progesterone Withdrawal in a Murine Model of Decidualization1

Abstract

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.

Granulocytes and Vascularization Regulate Uterine Bleeding and Tissue Remodeling in a Mouse Menstruation Model

“…While uterine natural killer (uNK) cells occur in high amounts during the implantation window, there is a marked increase in numbers of local macrophages and neutrophils prior to menstruation [20]. Similarly, an increase in endometrial macrophages and neutrophils in the decidualized mouse uterus has been reported previously [21], [22]. In those studies singular markers were used for identifying cells and only few tissue sections were analyzed by immunohistochemistry, which are not necessarily representative for the whole organ.…”

Application of iTRAQ to catalogue the skeletal muscle proteome in pigs and assessment of effects of gender and diet dephytinization

“…It has been shown that the production of new B-lineage precursor lymphocytes in murine bone marrow was suppressed by 20-30% after exposure to estrogen, which might explain the difference in muscle IGL [94]. Progesterone has been also shown to affect the expression of IGL mRNA in murine endometrium [95]. In contrast others reported increased levels of IgM, IgG, and IgA immunoglobulins in female rats, and demonstrated androgen interference with maturation processes of B-cells [92,93].…”

The importance of the macrophage within the human endometrium

“…Furthermore, macrophages have also been associated with glandular cell loss [12] and regulation of angiogenesis [50] during the menstrual phase. A tissue xenograft model of menstruation, developed by Cheng et al [62], has also shown that immune-related genes, including those known to be expressed by macrophages, are tightly regulated in response to progesterone withdrawal.…”