The Role of the FOXO1/β2-AR/p-NF-κB p65 Pathway in the Development of Endometrial Stromal Cells in Pregnant Mice under Restraint Stress

Restraint stress causes various maternal diseases during pregnancy. beta(2)-Adrenergic receptor (beta(2)-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 beta(2)-AR pathway in pregnant mice, has been unclear. The aim of this research was to investigate the beta(2)-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, beta(2)-AR, and even the protein levels of FOXO1 and beta(2)-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 beta(2)-AR was activated in endometrial stromal cells (ESCs). In addition, phosphorylated-nuclear factor kappa-B p65 (p-NF-kappa B p65) and its target genes decreased significantly when FOXO1 was inhibited. Overall, it can be said that the beta(2)-AR/FOXO1/p-NF-kappa B 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.

Automated summary

Restraint stress during pregnancy leads to increased levels of corticosterone, norepinephrine, and blood glucose, while decreasing estrogen levels. This stress also activates the beta(2)-AR/FOXO1/p-NF-kappa B pathway, resulting in increased oxidative stress in the maternal uterus. This study sheds light on the impact of psychological stress on pregnant women and their reproductive health.