Rapamycin In Prevention Of Ovarian Hyperstimulation Syndrome And Mechanism Research

With the progress of the society,people pay more attention to the reproductive health.The development of assisted reproductive technology(ART)provides for the infertility patients a Gospel.In the treatment of infertility,in vitro fertilization(IVF)technology and embryo transfer(ET)technology is both important and inseparable,the first step of in vitro fertilization is superovulation.Superovulation scheme is vary from person to person as individual sensitivity to the hormone.However,high ovarian response is directly correlated with risk of OHSS.The clinical manifestation of OHSS is abdominal bloating and distention,intravascular volume depletion,ascites,hemoconcentration,and ohguria following a fertility intervention involving the administration of exogenous FSH.Although the pathophysiology of OHSS has not been completely elucidated,there are perhaps more than one factor that interact to produce the vascular leakage that occurs in OHSS,such as vascular endothelial growth factor,the ovanan rein-angiotensin system,oestrogens,prolactin,prostaglandins,histamine,interleukins.mTOR signaling pathways plays an important role for angiogenesis in normal tissue and tumor.Therefore we propose a hypothesis,what does the role of mTOR signaling pathway play in the pathogenesis of OHSS.Whether mTOR signaling pathways regulating the process of a large number of new blood vessels formation and increased vascular permeability in the development of OHSS.Firstly,we used hormone overstimulation mouse ovarian successfully made a OHSS mice model.In our study,we tested the mTOR signaling pathways activity level in the mouse model.The level of p-S6K1 was significantly higher than control that prompt the activity of mTOR signaling pathways.Then we used a mTOR signaling pathway inhibitor Rapamycin succesfully resuce the increased ovary weight,corpus luteun number,E2 level,and vascular permeability of the OHSS mouse.In addition,we used ELISA method to detect IL-11 expression levels of ovarian tissues,according to the results,OHSS group mice IL-11 expression level was significantly higher than control.Through the RealTime-PCR detection of the extracellular matrix related gene expression level during corpus luteum formation and luteal tissue reconstruction,we find that a2M expression level of OHSS group is significantly higher than COH group,and Rapamycin group is dropped significantly than OHSS group.In addition,immunohistochemical results consistent with this trend.This provides a new clew in the research of pathophysiology development mechanism of OHSS.