title: Restraint stress delays endometrial adaptive remodeling during mouse embryo implantation.
abstract: In mice, previously, we showed that restraint stress reduces the number of embryo implantation sites in the endometrium. Here, we hypothesized that the uterine microenvironment is altered by restraint stress and consequently is suboptimal for embryo implantation. On embryonic day 1 (E1), 60 of 154 pregnant CD1 mice underwent restraint stress (4 h), repeated daily to E3, E5 or E7 (n = 10 mice per group). Restraint stress decreased food intake and suppressed body weight gain on E3, E5 and E7. Restraint stress decreased the actual and relative weight (percent body weight) of uterus and ovary on E5 (by 14.9%, p = 0.03; 16.1%, p = 0.004) and E7 (by 16.8%, p = 0.03; 20.0%, p = 0.01). Morphologically, restraint stress decreased relative endometrial area (by 8.94-18.8%, p = 0.003-0.021) and uterine gland area (by 30.6%, p < 0.01 on E3 and 44.5%, p < 0.01 on E5). Immunohistochemistry showed that restraint stress decreased microvessel density (by 12.9-70.5%, p < 0.01) and vascular endothelial growth factor expression (by 14.6-45.9%, p = 0.007-0.02). Restraint stress decreased by 32.4-39.8% (p = 0.002-0.01) the mean optical density ratio for proliferating cell nuclear antigen/terminal deoxynucleotidyl transferase dUTP nick end labeling. Methyl thiazolyl tetrazolium assay showed a dose-dependent decrease in proliferative activity of endometrial stromal cells (from 52 of 154 pregnant E5 control mice) incubated with H2O2 (100-1000 μM) in vitro. These findings supported the hypothesis that restraint stress negatively influences endometrial adaptive remodeling via an oxidative stress pathway, which resulted in fewer implantation sites.
authors.affiliation: a Laboratory of Veterinary Anatomy , College of Animal Medicine, China Agricultural University , Beijing , China.
authors.forename: Guanhui
authors.initials: G
authors.lastname: Liu
authors.affiliation: a Laboratory of Veterinary Anatomy , College of Animal Medicine, China Agricultural University , Beijing , China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Dong
authors.affiliation: a Laboratory of Veterinary Anatomy , College of Animal Medicine, China Agricultural University , Beijing , China.
authors.forename: Zixu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: a Laboratory of Veterinary Anatomy , College of Animal Medicine, China Agricultural University , Beijing , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cao
authors.affiliation: a Laboratory of Veterinary Anatomy , College of Animal Medicine, China Agricultural University , Beijing , China.
authors.forename: Yaoxing
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D004435:Eating / Q000502:physiology; D010064:Embryo Implantation / Q000502:physiology*; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D010053:Ovary / Q000378:metabolism*; D011247:Pregnancy; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D014599:Uterus / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D006861:Hydrogen Peroxide
keywords: Apoptosis; endometrial adaptive remodeling; endometrial stromal cells; pregnant mice; restraint stress; uterine microvasculature