Effect of stress exposure before pregnancy on subsequent pregnancy outcomes in mice

doi:10.3877/cma.j.issn.1674-0785.2023.04.012

Abstract

Abstract:

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.

Key words: Stress, Corticosterone, Serum- and glucocorticoid-inducible kinase-1, Glucocorticoid receptor, Adverse pregnancy outcomes

Xin Wang, Lin Liu, Zhejia Wen, Chunling Liu, Hong Zhang, Fang Lyu. Effect of stress exposure before pregnancy on subsequent pregnancy outcomes in mice[J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(04): 431-437.

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Figures/Tables 5

References 23

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分组	体重（g）
分组	基础	第3天	第6天	第9天	第12天	第15天	第18天	第21天	第24天
对照组	18.13±0.13	18.24±0.18	18.66±0.15	18.82±0.20	18.59（18.45，19.12）	19.32±0.16	19.63±0.20	20.25±0.31	21.19±0.32
皮质酮处理组	18.19±0.13	18.38±0.16	18.43±0.15	18.77±0.15	18.49±0.16	18.69±0.13	18.30±0.14	18.89±0.20	19.04±0.14
t/Z值	-0.305	-0.593	1.064	0.222	-1.041	3.026	5.542	3.837	6.126
P值	0.763	0.557	0.295	0.826	0.302	0.005	P＜0.001	0.001	P＜0.001

分组	体重（g）
分组	基础	第3天	第6天	第9天	第12天	第15天	第18天	第21天	第24天
对照组	18.13±0.13	18.24±0.18	18.66±0.15	18.82±0.20	18.59（18.45，19.12）	19.32±0.16	19.63±0.20	20.25±0.31	21.19±0.32
皮质酮处理组	18.19±0.13	18.38±0.16	18.43±0.15	18.77±0.15	18.49±0.16	18.69±0.13	18.30±0.14	18.89±0.20	19.04±0.14
t/Z值	-0.305	-0.593	1.064	0.222	-1.041	3.026	5.542	3.837	6.126
P值	0.763	0.557	0.295	0.826	0.302	0.005	P＜0.001	0.001	P＜0.001

	CORT	ACTH	5-HT
对照组	0.15±0.03	0.45±0.16	443.93±35.97
皮质酮处理组	0.63±0.13	1.26±0.27	426.59±39.43
t值	-4.012	-2.747	0.302
P值	0.048	0.040	0.769

	CORT	ACTH	5-HT
对照组	0.15±0.03	0.45±0.16	443.93±35.97
皮质酮处理组	0.63±0.13	1.26±0.27	426.59±39.43
t值	-4.012	-2.747	0.302
P值	0.048	0.040	0.769

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