Restraint Stress On Females During The Preimplantation Period Impairs Embryo Development:a Mechanistic Study Using The Mouse Model

The reproductive function can be supressed under different stressed conditions, such as infections, malnutrition, restraint stress, strenuous exercise, surgical trauma and so on. A number of studies show that high levels of psychological stress is an important factor to induce poor fertility.The psychological stress can induce oxidative stress, and the oxidative stress can influence a series of reproductive physiological process including oocyte maturation, fertilization, embryo development and gestation. Further, ROS could result in embryo fragmentation and thus increase the apoptosis. The embryos locate in the oviduct and have no direct relation with mother during the preimplantation period. Howere, there are no reports about how the mother influnces the embryo development under stress. To explore the influnece about stress on preimplantation embryos and the mechanisms, we began to study using a mouse model. Virgin females were placed with males and checked daily at 07:30 for copulatory plugs. Upon detection of a vaginal plug, female mice were stressed at 16:00 of the first day (D1) for 24h (early 24h S) and 48h (48h S) respectively, as well as the female mice in 16:00 of the second day (D2) for 24h (late 24h S). Mice without stress were as controls. Results indicated that mice under continuous stress for 48h have a poorer embryo development than others. We take advantage of this model and come to conclutions as follows. Restraint stress on females during the preimplantation period increses the levels of CRH and cortisol, cause the oxidant stress and elevate the level of oxidation. At the same time, the modle can cause increased CRH and cortisol in oviducts, and make oxidant stress occured in the oviducts. CRH and cortisol interact with thier receptors which cause the increase of CRHR1 and reduce of GR, which promote oxidant stress and induce apoptosis of oviduct epithelium. The apoptosis of oviduct epithelium cause the increase of TNF-? which react with receptor on embryos and result in the reduced embryo development. Furthermore, the apoptosis of oviduct epithelium induce decline of IGF-1 and BDNF and result in deficiency of embryo development.