Progesterone, the maternal immune system and the onset of parturition in the mouse
Progesterone, the maternal immune system and the onset of parturition in the mouse
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DOI：
10.1093/biolre/iox146
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发表时间：
2018-03-01
影响因子：
3.6
通讯作者：
Johnson, Mark R.
中科院分区：
文献类型：
--
作者：
Edey, Lydia F.;Georgiou, Hector;Johnson, Mark R.
孕激素（P4）在局部（子宫）和全身先天免疫系统、子宫肌层连接蛋白43（Cx-43）和环氧化酶2（考克斯-2）表达以及分娩开始中的作用在（i）足月分娩的未处理小鼠;（ii）用RU 486处理的E16小鼠中进行了检测。（iii）在用P4处理以预防足月分娩的小鼠中。在幼稚小鼠中，子宫肌层中性粒细胞和单核细胞数量在E18达到峰值，并随着分娩的开始而下降。相比之下，循环单核细胞没有变化，虽然中性粒细胞随着妊娠增加，但在整个妊娠期间没有变化。子宫肌层中大多数趋化因子/细胞因子、Cx-43和考克斯-2的mRNA和蛋白水平随着分娩而增加，但在分娩前没有增加。在RU 486诱导分娩的情况下，子宫肌层和全身中性粒细胞数量在分娩前增加，而子宫肌层单核细胞数量仅在分娩时增加。子宫肌层趋化因子/细胞因子mRNA丰度增加分娩，但蛋白质水平达到峰值早在4.5和9小时后RU 486。Cx-43，但不是考克斯-2，mRNA表达和蛋白水平增加之前的分娩开始。在用P4处理的小鼠中，子宫肌层单核细胞（但不是中性粒细胞）数量的妊娠相关增加被阻止，并且Cx-43和考克斯-2的表达减少。在补充P4的E20，子宫肌层趋化因子/细胞因子和白细胞数量增加，但不增加Cx-43和考克斯-2表达。这些数据表明，在怀孕期间，P4通过mRNA依赖和独立的机制控制子宫肌层单核细胞浸润、细胞因子和促分娩因子的合成，并且随着P4的长期补充，P4的作用被抑制，导致子宫肌层炎症增加。
The role of progesterone (P4) in the regulation of the local (uterine) and systemic innate immune system, myometrial expression of connexin 43 (Cx-43) and cyclooxygenase 2 (COX-2), and the onset of parturition was examined in (i) naive mice delivering at term; (ii) E16mice treated with RU486 (P4-antagonist) to induce preterm parturition; and (iii) in mice treated with P4 to prevent term parturition. In naive mice, myometrial neutrophil and monocyte numbers peaked at E18 and declined with the onset of parturition. In contrast, circulating monocytes did not change and although neutrophils were increased with pregnancy, they did not change across gestation. The myometrial mRNA and protein levels of most chemokines/cytokines, Cx-43, and COX-2 increased with, but not before, parturition. With RU486-induced parturition, myometrial and systemic neutrophil numbers increased before and myometrial monocyte numbers increased with parturition only. Myometrial chemokine/cytokine mRNA abundance increased with parturition, but protein levels peaked earlier at between 4.5 and 9 h post-RU486. Cx-43, but not COX-2, mRNA expression and protein levels increased prior to the onset of parturition. In mice treated with P4, the gestation-linked increase in myometrial monocyte, but not neutrophil, numbers was prevented, and expression of Cx-43 and COX-2 was reduced. On E20 of P4 supplementation, myometrial chemokine/cytokine and leukocyte numbers, but not Cx-43 and COX-2 expression, increased. These data show that during pregnancy P4 controls myometrial monocyte infiltration, cytokine and prolabor factor synthesis via mRNA-dependent and independent mechanisms and, with prolonged P4 supplementation, P4 action is repressed resulting in increased myometrial inflammation.Summary SentenceProgesterone independently regulates the maternal immune system and the onset of parturition in the mouse.