Restraint stress inhibits mouse implantation: temporal window and the involvement of HB-EGF, estrogen and progesterone.
It is known that psychological stress affects reproduction in women, but it is unknown whether the effect is by impairing implantation. Although studies suggest that long periods of auditory or restraint stress may inhibit implantation in rats and mice, the exact stage of pregnancy at which stress impairs implantation is unclear. Furthermore, whether stress impairs implantation by decreasing the heparin-binding epidermal growth factor-like growth factor (HB-EGF), estrogen and/or progesterone and whether by acting on embryos or on the uterus need further investigations. In this study, a 24-h restraint stress was initiated at 15:30 of day 3 (regimen 1) or at 07:30 (regimen 2) or 15:30 of day 4 (regimen 3) of pregnancy (vaginal plug  =  day 1) to observe effects of restraint stress applied at different peri-implantation stages on implantation. Among the three regimens, whereas regimens 1 and 3 affected neither term pregnancy nor litter size, regimen 2 reduced both. Further observations indicated that regimen 2 of restraint stress also delayed blastocyst hatching and the attachment reaction, decreased serum concentrations of progesterone and estradiol, and down regulated the expression of HB-EGF in both the endometrium and blastocysts. Taken together, the results suggested that restraint stress inhibited mouse implantation in a temporal window-dependent manner and by impairing blastocyst activation and hatching and uterine receptivity via down-regulating HB-EGF, estrogen and progesterone. Thus, the stress applied within the implantation window impaired implantation by acting on both embryos and the uterus.
College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai-an City, P. R. China.
Li-Hua
LH
Zhao
Xiang-Zhong
XZ
Cui
Hong-Jie
HJ
Yuan
Bo
B
Liang
Liang-Liang
LL
Zheng
Yu-Xiang
YX
Liu
Ming-Jiu
MJ
Luo
Jing-He
JH
Tan
D000818:Animals; D010064:Embryo Implantation / Q000502:physiology*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D066257:Heparin-binding EGF-like Growth Factor / Q000378:metabolism*; D008297:Male; D051379:Mice; D011247:Pregnancy; D011256:Pregnancy Outcome; D011374:Progesterone / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology*
D004967:Estrogens; D066257:Heparin-binding EGF-like Growth Factor; D011374:Progesterone