Restraint stress induces uterine microenvironment disorder in mice during early pregnancy through the β2-AR/cAMP/PKA pathway.

During pregnancy, uterus undergoes the environment adaptation as part of a program of development. In the world, one in four people worldwide suffer from mental illness, especially pregnant women. β-Adrenergic receptor (β-AR) is an important regulator that converts environmental stimuli into intracellular signals in mice uterus. CD-1 (ICR) mice undergone restraint stress, which was a case in model to simulate the psychological stress. The plasma and implantation sites in uterus were obtained and examined. PCR analysis demonstrated that β2-AR expression levels in embryo day (E) 3, 5 and 7 were kept at a significantly higher level (p < 0.05) under restraint stress and higher than β1-AR and β3-AR in different gestation ages. The β2-AR protein levels were obviously increased (p < 0.05) due to the markedly elevated norepinephrine (NE) concentration (p < 0.05). In our previous study, restraint stress can induce the apoptosis and inflammation. Also, the matrix metalloprotein-9 (MMP-9) was decreased significantly (p < 0.05) under restraint stress. Meanwhile, Caspase3, p-NF-κB p65 and p-ERK1/2 were obviously increased (p < 0.05) in the work. In vitro studies showed that the p-ERK1/2 and Caspase-3 levels were raised (p < 0.05) after β2-AR was activated. However, they were decreased when PKA was blocked. The protein levels of Caspase-3 were reduced when ERK and NF-κB were blocked (p < 0.05). In conclusion, the β2-AR/cAMP/PKA pathway promoted apoptosis and affected the development of the uterus through the ERK and NF-κB signaling pathway. The findings of this study may provide evidence for female reproduction under psychological stress.