Promotion of Human Early Embryonic Development and Blastocyst Outgrowth In Vitro Using AutocrineParacrine Growth Factors 英文参考文献.docVIP

PromotionofHumanEarlyEmbryonicDevelopmentand BlastocystOutgrowthInVitroUsingAutocrine/Paracrine GrowthFactors KazuhiroKawamura1,2.,YuanChen3.,YiminShu1.,YuanCheng1,JieQiao3,BarryBehr1, ReneeA.ReijoPera1,AaronJ.W.Hsueh1* 1ProgramofReproductiveandStemCellBiology,DepartmentofObstetricsandGynecology,StanfordUniversitySchoolofMedicine,Stanford,California,UnitedStatesof America, 2Department ofObstetrics and Gynecology, Akita University Graduate School of Medicine, Akita, Japan, 3Center ofReproductiveMedicine,Department of ObstetricsandGynecology,PekingUniversityThirdHospital,Beijing,People’sRepublicofChina Abstract Studies using animal models demonstrated the importance of autocrine/paracrine factors secreted by preimplantation embryos and reproductive tracts for embryonic development and implantation. Although invitro fertilization-embryo transfer(IVF-ET)isanestablishedprocedure,thereisnoevidencethatpresentcultureconditionsareoptimalforhuman early embryonic development. In this study, key polypeptide ligands known to be important for early embryonic developmentinanimalmodelsweretestedfortheirabilitytoimprovehumanearlyembryodevelopmentandblastocyst outgrowthinvitro.Weconfirmedtheexpressionofkeyligand/receptorpairsincleavageembryosderivedfromdiscarded humantri-pronuclearzygotesandinhumanendometrium.Combinedtreatmentwithkeyembryonicgrowthfactors(brain- derived neurotrophic factor, colony-stimulating factor, epidermal growth factor, granulocyte macrophage colony- stimulatingfactor,insulin-likegrowthfactor-1,glialcell-linederivedneurotrophicfactor,andartemin)inserum-freemedia promoted.2.5-foldthedevelopmentoftri-pronuclearzygotestoblastocysts.Fornormallyfertilizedembryos,day3surplus embryosculturedindividuallywiththekeygrowthfactorsshowed.3-foldincreasesinthedevelopmentof6–8cellstage embryos to blastocysts and .7-fold increase in the proportion of high quality blastocysts based on Gardner’s criteria. Growth factor treatment also led to a 2-fold promotion of blastocyst out