Graduate School, Peking Union Medical College, 100730 Beijing, People's Republic of China.
Hum Reprod. 2013 Jun;28(6):1670-8. doi: 10.1093/humrep/det052. Epub 2013 Mar 19.
Is there a critical period of progesterone (P4) withdrawal in a mouse menstrual-like model, and at what time after P4 withdrawal endometrial breakdown become irreversible?
Our results showed that a 12-16 h critical period of P4 withdrawal exists in the mouse menstrual-like model.
P4 withdrawal is the trigger for endometrial breakdown and shedding during menstruation. To date, the molecular mechanisms responsible for endometrial breakdown have not been fully elucidated. In an ovariectomized macaque model, P4 replacement could reduce or block menses during a period of 36-48 h after P4 withdrawal, but after this, P4 supplementation did not reduce or block menses. Thus, in the macaque, a critical period of P4 withdrawal lasting 36-48 h exists before menses.
STUDY DESIGN, SIZE, DURATION: We created a mouse menstrual-like model and restored P4 at four time points. The total number of mice was 120 and the duration of treatment was 26 days.
PARTICIPANTS, SETTING, METHODS: A mouse menstrual model was characterized by endometrial morphology and plasma P4 levels. P4 was then replaced at 8, 12, 16 and 20 h after the removal of P4 implants. Vaginal smears, endometrial morphology, plasma P4 levels and expression patterns of matrix metalloproteinases (MMP-2, MMP-3, MMP-9, MMP-10, MMP-11 and MMP-13) were investigated.
Replacement of P4 at 8 and 12 h blocked menstrual-like bleeding and endometrial shedding; however, replacement at 16 and 20 h did not suppress bleeding or shedding. Furthermore, P4 replacement at 12 h inhibited the expression of all latent or active MMPs; however, replacement at 16 h inhibited only pMMP-13.
LIMITATIONS, REASONS FOR CAUTION: Although determination of the critical period in vivo using a mouse model was successfully demonstrated, the mechanisms of P4 regulation need to be further explored.
The experimental opportunities provided by the mouse model will facilitate understanding the role of P4 in the regulation of menstruation and help to identify new targets for the clinical intervention of menstrual disorders.
在小鼠类似月经模型中，孕酮（P4）撤退是否存在关键时期，以及在 P4 撤退后多久，子宫内膜破裂变得不可逆转？
我们的结果表明，在小鼠类似月经模型中存在 12-16 小时的 P4 撤退关键时期。
P4 撤退是月经期间子宫内膜破裂和脱落的触发因素。迄今为止，负责子宫内膜破裂的分子机制尚未完全阐明。在去卵巢的猕猴模型中，P4 替代可在 P4 撤退后 36-48 小时内减少或阻断月经，但在此之后，P4 补充并不能减少或阻断月经。因此，在猕猴中，在月经前存在持续 36-48 小时的 P4 撤退关键时期。
研究设计、大小、持续时间：我们创建了一个小鼠类似月经模型，并在四个时间点恢复 P4。总共 120 只小鼠，治疗持续 26 天。
参与者、设置、方法：通过子宫内膜形态和血浆 P4 水平来描述小鼠月经模型。然后在去除 P4 植入物后 8、12、16 和 20 小时替换 P4。研究了阴道涂片、子宫内膜形态、血浆 P4 水平以及基质金属蛋白酶（MMP-2、MMP-3、MMP-9、MMP-10、MMP-11 和 MMP-13）的表达模式。
在 8 小时和 12 小时替换 P4 可阻断类似月经的出血和子宫内膜脱落；然而，在 16 小时和 20 小时替换则不能抑制出血或脱落。此外，在 12 小时替换 P4 抑制了所有潜伏或活性 MMP 的表达；然而，在 16 小时替换仅抑制了 pMMP-13。
局限性、谨慎的原因：虽然使用小鼠模型成功地确定了体内的关键时期，但 P4 调节的机制仍需进一步探讨。
小鼠模型提供的实验机会将有助于理解 P4 在调节月经中的作用，并有助于确定月经紊乱临床干预的新靶点。
