The Initiatory Study Of The Expression And Functional Role Of P110δ In Murine Placentation

Background and experiment purpose: The reproduction of life is foundation of th e sustainable development of human society. But with the continuous development o f human civilization, worldwidely speaking, infertility rate increased significantly, be cause the various external factors such as work stress and environmental pollution. Human reproductive capacity has lit the Warning lights. Reproductive health has aro used people’s higher tension and emphasis. As far as the infertility, nearly half of it is unexplained recurrent spontaneous abortion, which is regarded to be correlated w ith immune factors and hereditary factors by fertility experts. Phosphatidylinositol 3-kinase/ Serine threonine protein kinase(PI3K/Akt) is a vital intracellular signal trans duction pathway that has enzyme activity, which can regulate cell proliferation, apop tosis, differentiation, inflammatory reaction and immune response. PI3 K has four cat alytic subunits: p110α, p110β, p110δ and p110γ. There were reports that p110 alpha or beta deficiency lead to embryonic lethal due to defective neovascularization. In t his study, we found that mice with mutant p110δ showed drastically reduced fertilit y number, and further study showed that the fetal losing mainly occurred in mid-ge station, when placentation happened. This experiment intends to explore the expressi on location and functional role of p110δ in reproductive system preliminarily, especi al y in placentation.Methods and results: Firstly, to breed the mutant p110δ model mice(p110δD910A/D910A) and record the mice reproductive capacity. We found that p110δD910A/D910 A mice litter less than the normal, and this abnormal phenomenon is mainly associated with the female. Based on further observation, we found that the reduction of birth number is actual y the results of abortion after placentation. After the histological observation and pathological detection to the relevant reproductive organs, we detected negative influence on vascular system in decidua, embryolemma and the placenta when p110δ is mutant, such as intermittent blood vessel and sparse vascular net. In addition, p110δ specifically and highly expresses in the parietal trophoblast giant cell during decidual period. Once the pregnant mice lacked the activation of p110δ and its downstream pathway, the trophoblast cels’ normal function would be interfered, including cell proliferation, differentiation and invasion related secretion of MMPs. Finally, the above experimental results, which are related to angiogenesis and trophoblastic cells function, were further verified through detecting the relative gene expression level by PCR technology.Conclusion: p110δ mutation caused abnormal angiogenesis/vascular remodeling and the functions of trophoblast cel s during gestation period, which will promote fetal abortion in the middle of gestation, placentation period, subsequently.