title: Restraint stress alters immune parameters and induces oxidative stress in the mouse uterus during embryo implantation.
abstract: The influence of stress on embryo implantation is not well understood. Prior studies have focused on later gestational stages and the long-term impact of stress on immune function. The objective of this study is to investigate the effects of restraint stress on the immune parameters and the oxidative states of the uterus during implantation. In this study, pregnant CD1 mice were subjected to restraint stress (4 h/d) on embryonic day 1 (E1) and sacrificed on E3, E5, and E7. Maternal plasma corticosterone (CORT) secretion and implantation sites in the uterus were examined. The uterine (excluding embryos) homogenate and uterine lymphocytes were collected to examine oxidative stress states and associated immune parameters. The results demonstrated that restraint stress increased maternal plasma CORT secretion and reduced the number of implantation sites by 15.3% on E5 and by 26.1% on E7. Moreover, restraint stress decreased the density of uterine natural killer (uNK) cells in the endometrium by 22.1-47.9% and increased the density of mast cells in the myometrium by 55.6-76.9%. Restraint stress remarkably decreased the CD3(+)CD4(+) T/CD3(+)CD8(+) T cell ratio (by 26.2-28.9%) and attenuated uterine lymphocyte proliferation and secretion of cytokines. In addition, restraint stress threatened the intracellular equilibrium between oxidants and antioxidants, resulting in decreased glutathione peroxidase (GSH-PX) (32.2% and 45.7%), superoxide dismutase (SOD) (15.5% and 26.1%), and total antioxidant capacity (T-AOC) (18.4% and 18.2%) activities and increased malondialdehyde (MDA) (34.4% and 43.0%) contents on E5 and E7. In conclusion, these findings demonstrate that restraint stress causes abnormal implantation and negatively impacts immune parameters in association with oxidative stress in mice.
authors.affiliation: Laboratory of Veterinary Anatomy, College of Animal Medicine, China Agricultural University , Beijing , China.
authors.forename: Guanhui
authors.initials: G
authors.lastname: Liu
authors.forename: Yulan
authors.initials: Y
authors.lastname: Dong
authors.forename: Zixu
authors.initials: Z
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Cao
authors.forename: Yaoxing
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D016516:CD4-CD8 Ratio; D049109:Cell Proliferation; D002478:Cells, Cultured; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D010064:Embryo Implantation; D005260:Female; D005865:Gestational Age; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress; D011247:Pregnancy; D012149:Restraint, Physical / Q000009:adverse effects*; D013312:Stress, Physiological; D013315:Stress, Psychological / Q000097:blood / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014599:Uterus / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D016207:Cytokines; D003345:Corticosterone
keywords: Immune parameters; implantation sites; oxidative stress; pregnant mice; restraint stress; uterus