Laboratory of Neurobiology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, China Agricultural University, Beijing 100193, China.
Int J Mol Sci. 2021 Feb 2;22(3):1478. doi: 10.3390/ijms22031478.
Restraint stress causes various maternal diseases during pregnancy. β-Adrenergic receptor (β-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 β-AR pathway in pregnant mice, has been unclear. The aim of this research was to investigate the β-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, β-AR, and even the protein levels of FOXO1 and β-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 β-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 β-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.
束缚应激会导致孕妇出现各种疾病。β-肾上腺素能受体（β-AR）和叉头转录因子 O1 类（FOXO1）不仅是应激反应的关键因素，也是生殖的关键因素。然而，FOXO1 在束缚应激导致怀孕小鼠β-AR 途径变化中的作用尚不清楚。本研究旨在探讨束缚应激对β-AR 途径的影响及其对母体子宫氧化应激的影响。在研究中，通过在透明通风装置中束缚怀孕第 5 天（P5）、第 10 天（P10）、第 15 天（P15）和第 20 天（P20）以及非怀孕第 5 天（NP5）的母鼠来进行束缚应激处理，然后在这些时间点处死母鼠。束缚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）水平降低。此外，束缚应激增加了子宫和卵巢中 FOXO 家族、β-AR 的 mRNA 水平，甚至增加了 FOXO1 和β-AR 的蛋白水平。此外，束缚应激增加了子宫的氧化应激水平。在体外，当子宫内膜基质细胞（ESCs）中的β-AR 被激活时，FOXO1 的蛋白水平也明显增加。此外，当抑制 FOXO1 时，磷酸化核因子 kappa-B p65（p-NF-κB p65）及其靶基因显著减少。总的来说，束缚应激可激活怀孕小鼠的β-AR/FOXO1/p-NF-κB p65 途径。本研究为孕妇心理应激的起源提供了科学依据。
