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Updated: Nov 27, 2025
Using a Murine Model of Psychosocial Stress in Pregnancy as a Translationally Relevant Paradigm for Psychiatric Disorders in Mothers and Infants
Published on: June 13, 2021
Restraint stress induces uterine microenvironment disorder in mice during early pregnancy through the β2-AR/cAMP/PKA
Jiayin Lu1, Guanhui Liu1,2, Zixu Wang1
1Laboratory of Neurobiology, College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China.
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.
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.
