Study On Relationship Between Dysfunction Of Kisspeptin/GPR54and The Pathogenesis Of Unexplained Recurrent Spontaneous Abortion

Objective: To investigate the expression of kisspeptin/GPR54at maternal-fetalinterface of women with unexplained recurrent spontaneous abortion（URSA） and theprobable pathogenesis of recurrent spontaneous abortion.Methods:1. Clinical research: Trophoblastic and decidual tissues were collectedfrom32URSA women who miscarried a genetically normal fetus and35women who hadvoluntary abortion. Kisspeptin, GPR54, PR and PIBF were investigated withimmunohistochemistry.2. Animal experiments:(1) The resorption-prone mating of CBA/J×DBA/2mice were established as the model of spontaneous abortion and thenonabortion-prone mating of CBA/J×BALB/c mice were used as the model of normalpregnancy. The placenta tissues were collected on day9and day14of gestation, thenkisspeptin, GPR54, PR and PIBF were investigated with immunohistochemistry. Theembryo resorption rate was separately counted on the two days.(2) Choosing theresorption-prone mating of CBA/J×DBA/2mice, which were divided equally into twogroups, the group injected with progesterone every two days after mating wasthe experimental group, the other one injected with tea oil at the same dose on the samedays was the control group. The placenta tissues were collected on day9and day14ofgestation, and kisspeptin, GPR54, PR and PIBF were investigated withimmunohistochemistry. The embryo resorption rate was also separately counted.Expression differences of kisspeptin, GPR54, PR and PIBF were compared between thetwo groups in order to observe the changes of kisspeptin, GPR54, PR and PIBF expressioninduced by progesterone. Results:1. Kisspeptin, GPR54and PIBF expression in syncytiotrophoblasts were significantlydecreased in URSA women as compared to controls (P <0.05). Kisspeptin, PR and PIBFexpression in deciduas were significantly decreased in URSA women as compared tocontrols (P <0.05). GPR54expression in deciduas nearly had no difference among studygroups and controls. PR expression was negative in deciduas both of the two groups.2. The embryo resorption rate of the resorption-prone mating of CBA/J×DBA/2miceon day9and day14of gestation were significantly higher than that of thenonabortion-prone mating of CBA/J×BALB/c mice (29.17%vs9.09%，27.27%vs5.41%)(P <0.05). And the expression of kisspeptin, GPR54, PR and PIBF at maternal-fetalinterface of spontaneous abortion mouse models were significantly lower than the normalpregnancy mouse models (P <0.05).3. Progesterone reduced the embryo resorption rate of the spontaneous abortionmouse models and increased the expression of kisspeptin, GPR54, PR and PIBF atmaternal-fetal interface（P<0.05）.Conclusion:1. The lower expression of kisspeptin at maternal-fetal interface of URSA womenindicates that dysfunction of kisspeptin/GPR54is associated with unexplained recurrentspontaneous abortion.2. The expression of kisspeptin at maternal-fetal interface is collaborative with theexpression of PIBF, which indicates that kisspeptin/GPR54system’s mechanism of actionmay be related to P/PR and PIBF.3. The supplement of progesterone can increase the expression of kisspeptin and PIBFand reduce the embryo resorption rate, indicating that kisspeptin plays an important role inthe pathogenesis of unexplained recurrent spontaneous abortion.