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首页> 外文期刊>Human Reproduction >A critical period of progesterone withdrawal precedes endometrial breakdown and shedding in mouse menstrual-like model
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A critical period of progesterone withdrawal precedes endometrial breakdown and shedding in mouse menstrual-like model

机译：在小鼠月经样模型中，黄体酮退出的关键时期是子宫内膜破裂和脱落之前。

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STUDY QUESTION 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?STUDY ANSWEROur results showed that a 12-16 h critical period of P4 withdrawal exists in the mouse menstrual-like model. WHAT IS KNOWN ALREADY 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, METHODSA 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.MAIN RESULTS AND THE ROLE OF CHANGEReplacement 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. WIDER IMPLICATIONS OF THE FINDINGS 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. STUDY FUNDING/COMPETING INTEREST(S) None of the authors has any competing interest.
机译：研究问题在小鼠月经样模型中是否存在孕激素（P4）退出的关键时期，并且在P4退出后什么时候子宫内膜破裂变得不可逆？研究结果表明，在小鼠中存在P16退出的12-16 h关键时期。小鼠月经样模型。 P4退出是月经期间子宫内膜破裂和脱落的触发因素。迄今为止，尚未完全阐明引起子宫内膜破裂的分子机制。在切除卵巢的猕猴模型中，P4替代可以在撤消P4后36-48小时内减少或阻塞月经，但此后，补充P4并没有减少或阻塞月经。因此，在猕猴中，P4停药的关键时期持续了36-48小时。研究设计，大小，持续时间我们创建了一个小鼠月经样模型，并在四个时间点恢复了P4。小鼠总数为120只，治疗时间为26天。通过子宫内膜形态学和血浆P4水平表征小鼠，环境，方法。然后在移除P4植入物后的8、12、16和20 h更换P4。研究了阴道涂片，子宫内膜形态，血浆P4水平和基质金属蛋白酶（MMP-2，MMP-3，MMP-9，MMP-10，MMP-11和MMP-13）的表达模式。主要结果和改变的作用P4在8和12 h阻断月经样出血和子宫内膜脱落。但是，在16和20 h进行更换不能抑制出血或脱落。此外，在12 h置换P4会抑制所有潜在或活跃MMPs的表达。然而，在16 h更换仅抑制pMMP-13。局限性，注意事项的原因尽管已成功证明了使用小鼠模型确定体内关键期的方法，但仍需进一步探索P4调节的机制。结果的更广泛含义小鼠模型提供的实验机会将有助于理解P4在月经调节中的作用，并有助于确定临床干预月经失调的新靶点。研究资助/竞争兴趣没有作者有任何竞争兴趣。

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