Xu X B, He B, Wang J D
Department of Cell Biology, National Research Institute for Family Planning, Beijing 100081, People's Republic of China.
Hum Reprod. 2007 Dec;22(12):3184-91. doi: 10.1093/humrep/dem312. Epub 2007 Oct 4.
Cyclic shedding of the endometrium is unique to menstruating species, and mouse menstruation models by physiologic progesterone withdrawal have been previously reported. Since progesterone action ablated pharmacologically may provide more insight into the mechanism of action, a mouse menstruation model using mifepristone was established.
Mifepristone was administered following oil-induced decidualization in ovarectomized mice primed with hormones. Morphology, hormone levels, leukocytes and apoptosis were evaluated over a period of 48 h after treatment. Vaginal smears were used to monitor bleedings.
Mifepristone induced menstrual-like changes. Tissue breakdown was drastic by 16 h, and the decidual zone was shed by 24 h while the mice bled. The endometrium regenerated from 24 h onwards and became completely restored by 48 h. These results are consistent with previous reports. However, although progesterone levels remained constant, estradiol levels increased after the treatment. The CD45(+) cells showed two peaks of increase at 16 h (breakdown phase) and 32 h (regeneration phase) (Leukocyte levels also increased in the unstimulated horns, but no breakdown changes occurred there). Moreover, apoptosis drastically increased by 16 h concurrent with tissue destruction. These results differed from those of the physiologic withdrawal models.
The pharmacologic withdrawal of progesterone by mifepristone successfully provoked a menstrual-like process in mice after artificial decidualization.
子宫内膜的周期性脱落是有月经的物种所特有的，此前已有通过生理性孕酮撤退建立小鼠月经模型的报道。由于药理学上消除孕酮作用可能会更深入地了解其作用机制，因此建立了使用米非司酮的小鼠月经模型。
在经激素预处理的去卵巢小鼠中，在油诱导蜕膜化后给予米非司酮。在治疗后的48小时内评估形态学、激素水平、白细胞和细胞凋亡情况。使用阴道涂片监测出血情况。
米非司酮诱导出类似月经的变化。到16小时时组织破坏剧烈，到24小时时蜕膜区脱落，此时小鼠出血。子宫内膜从24小时起开始再生，并在48小时时完全恢复。这些结果与先前的报道一致。然而，尽管孕酮水平保持恒定，但治疗后雌二醇水平升高。CD45(+)细胞在16小时（破坏期）和32小时（再生期）出现两个增加峰值（未受刺激的子宫角白细胞水平也升高，但未发生破坏变化）。此外，细胞凋亡在16小时时随着组织破坏而急剧增加。这些结果与生理性撤退模型的结果不同。
米非司酮药理学上的孕酮撤退在人工蜕膜化后成功地在小鼠中引发了类似月经的过程。
