Effect of stress exposure before pregnancy on subsequent pregnancy outcomes in mice
Objective:To investigate the effect of pre-pregnancy glucocorticoid administration as a stress factor on subsequent pregnancy outcomes in mice and the potential mechanism involved.Methods:Forty female BALB/c mice were randomly divided into a corticosterone (CORT) administration group and a control group. Mice in the CORT administration group were peritoneally injected with CORT at a dose of 20 mg/kg/d for 24 days, while the control group was given equal volume of the vehicle. Serum level of CORT, adrenocorticotropic hormone (ACTH), and 5-HT (5-hydroxytryptamine) were compared between the two groups. CORT treated female mice were bred with male BALB/c mice 2 weeks after the final injection and checked for vaginal plugs daily. The indexes of pregnancy outcomes were observed and compared between the two groups. E13.5-15.5 placentas were collected to analyze the expression of glucocorticoid receptor (GR) and serum-and glucocorticoid-inducible kinase-1 (SGK1) by immunohistochemistry.Results:Compared with the control mice, the immobility time in the forced swimming test were significantly longer in CORT treated mice (P=0.004), and serum levels of CORT and ACTH were significantly increased (P=0.048, P=0.040). The litter size (P=0.025) and litter weight (P=0.003) were significantly decreased with a significantly increased rate of resorption (P＜0.001) in CORT treated mice. Immunohistochemical analysis showed that the expression of GR in the decidua basalis and labyrinth (P=0.037 and P=0.001, respectively) in the CORT administration group significantly increased, while the expression of SGK1 in the decidua (P=0.048) was significantly decreased.Conclusion:A mouse stress model has been successfully induced by CORT, and there is a significantly increased rate of implantation resorption, and reduced litter size and litter weight during subsequent pregnancy in model mice. The pregnancy loss is related with increased GR in the decidua basalis and labyrinth but decreased SGK1 in the decidua. High level of CORT exposure before pregnancy has a significant effect on subsequent pregnancy outcomes.
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