Mechanism Of Influencing Oocyte Development By Corticotropin-releasing Hormone And Fas System During Mouse Restraint Stress

With the development of the society and the progress of science and technology,life rhythm is faster,and the psychological pressure is bigger.Women who have a variety of roles are more susceptible to the influence of stress-related diseases.Stress can cause reproductive endocrine disorders or degenerative diseases and women premature aging.The hypothalamus-pituitary-adrenal axis(HPA)can be activated and induced an adverse effect on female reproductive system under psychological stress.CRH plays an important role in imparing mouse oocyte developmental potential during restraint stress,but the mechanism of CRH-induced ovarian cell apoptosis is unclear.In addition,studies have shown that stress activates the Fas signaling pathway.It is unclear whether there is a link between CRH and Fas signaling pathways during stress.Therefore,taking advantage of the restraint stress model,sustained restrainted for 24 h or 48 h.To investigate the effects of restraint stress on the apoptosis of ovarian cells(mural granulosa cells and oocytes),and the role of Fas signaling pathway and CRH in ovarian cell apoptosis,and to explore the specific mechanism of restraint stress impaired mouse oocyte developmental potential.Our research demonstrated that:(1)Compared with control,the rate of oocyte maturation in restraint stress 24 h or 48 h was not significant(P>0.05),which indicated that restraint stress 24 h or 48 h can not affect oocyte maturation.(2)Compared with control,the rate of 4-cell,blastocyst and blastocysts was not significant in restraint stress 24 h(P>0.05),which indicated that restraint stress 24 h can not affect oocyte developmental potential;Compared with control,the rate of 4-cell,blastocyst and blastocysts significantly decreased during embryonic development(P<0.05),which indicated that restraint stress 48 h impaired mouse oocyte developmental potential.(3)Compared with control and restraint stress 24 h group,the rate of apoptotic ovarian cell(mural granulosa cells and denuded oocytes)in restraint stress 48 h group significantly increased(P<0.05).(4)Compared with control and restraint stress 24 h group,quantification showed that restraint stress 48 h significantly increased Fas/FasL expression in mural granulosa cells(P<0.05).Similarly,significantly increased Fas expression in GV oocytes(P<0.05).(5)Compared with control and restraint stress 24 h group,in both serum and ovarian homogenates,the level of CRH significantly increased in restraint stress 48 h(P<0.05).And restraint stress 48 h significantly increased CRHR1 expression in mural granulosa cells(P<0.05).(6)CRHR1 antagonist(antalarmin)was injected in restraint stress 48 h,the rate of 4cell and blastocysts significantly increased compared with control mice(P<0.05).The expression of CRH in serum and ovary and the expression of CRHR1 in the granulosa cells were upregulated by the restraint stress,and the activation of Fas signal pathway induced ovarian cell apoptosis to damage the oocyte development potential.