The Role of the FOXO1/β(2)-AR/p-NF-κB p65 Pathway in the Development of Endometrial Stromal Cells in Pregnant Mice under Restraint Stress.
The Role of the FOXO1/β(2)-AR/p-NF-κB p65 Pathway in the Development of Endometrial Stromal Cells in Pregnant Mice under Restraint Stress.
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DOI：
10.3390/ijms22031478
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发表时间：
2021-02-02
影响因子：
5.6
通讯作者：
Dong Y
中科院分区：
文献类型：
--
作者：
Lu J;Chen Y;Wang Z;Cao J;Dong Y
约束压力导致怀孕期间的各种产妇疾病。β2-肾上腺素能受体（β2-AR）和叉头转录因子1类（FOXO1）不仅在应激过程中起关键作用，而且在生殖过程中起关键作用。然而，FOXO1在抑制应激中的作用，导致妊娠小鼠β2-AR通路的变化，一直不清楚。本研究旨在探讨抑制应激的β2-AR通路及其对母体子宫氧化应激的影响。在实验中，母鼠分别于妊娠第5天（P5）、妊娠第10天（P10）、妊娠第15天（P15）、妊娠第20天（P20）及非妊娠第5天（NP5）在牺牲前置于透明通气装置中进行约束应激处理。约束应激增加了血液皮质酮（CORT）、去甲肾上腺素（NE）和血糖水平，而雌二醇（E2）水平下降。抑制应激增加了子宫和卵巢中FOXO家族mRNA和β2-AR水平，甚至FOXO1和β2-AR蛋白水平。抑制应激使子宫氧化应激水平升高。在体外，当β2-AR在子宫内膜基质细胞（ESCs）中被激活时，FOXO1蛋白水平也明显升高。此外，磷酸化核因子κ b p65 （p-NF-κB p65）及其靶基因在FOXO1被抑制时显著降低。综上所述，妊娠小鼠在限制性应激下，β2-AR/FOXO1/p-NF-κB p65通路被激活。本研究为孕妇心理压力的来源提供了科学依据。
Restraint stress causes various maternal diseases during pregnancy. β2-Adrenergic receptor (β2-AR) and Forkhead transcription factor class O 1 (FOXO1) are critical factors not only in stress, but also in reproduction. However, the role of FOXO1 in restraint stress, causing changes in the β2-AR pathway in pregnant mice, has been unclear. The aim of this research was to investigate the β2-AR pathway of restraint stress and its impact on the oxidative stress of the maternal uterus. In the study, maternal mice were treated with restraint stress by being restrained in a transparent and ventilated device before sacrifice on Pregnancy Day 5 (P5), Pregnancy Day 10 (P10), Pregnancy Day 15 (P15), and Pregnancy Day 20 (P20) as well as on Non-Pregnancy Day 5 (NP5). Restraint stress augmented blood corticosterone (CORT), norepinephrine (NE), and blood glucose levels, while oestradiol (E2) levels decreased. Moreover, restraint stress increased the mRNA levels of the FOXO family, β2-AR, and even the protein levels of FOXO1 and β2-AR in the uterus and ovaries. Furthermore, restraint stress increased uterine oxidative stress level. In vitro, the protein levels of FOXO1 were also obviously increased when β2-AR was activated in endometrial stromal cells (ESCs). In addition, phosphorylated-nuclear factor kappa-B p65 (p-NF-κB p65) and its target genes decreased significantly when FOXO1 was inhibited. Overall, it can be said that the β2-AR/FOXO1/p-NF-κB p65 pathway was activated when pregnant mice were under restraint stress. This study provides a scientific basis for the origin of psychological stress in pregnant women.
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影响因子：
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发表时间：
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期刊：
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