The Effect Of Pregnancy-related Diseases On Cardiovascular System In Offspring And Its Mechanism

Part ? The effect of ovarian hyperstimulation syndrome on cardiovascular function of offspring:a cohort studyObjective:To assess the effect of ovarian hyperstimulation syndrome(OHSS)on cardiovascular function of offspring.Materials and Methods:The cohort study recruited 42 OHSS offspring,34 non-OHSS-In Vitro Fertilization(IVF)offspring and 48 spontaneously conceived offspring.The groups were matched with gestational age and birth weight.We assessed cardiovascular functions by Doppler echography.Results:Children of OHSS mothers showed a significantly decreased mitrat E/A ratio and impaired flow-mediated dilation compared with non-OHSS IVF and SC children.Ejection fraction,intima?media thickness and Arterial stiffness indices were similar in three groups.OHSS women showed higher serum estradiol level in early pregnancy and in umbilical blood.Conclusions:Children bom to ovarian hyperstimulated women displayed cardiovascular dysfunctions.The underlying mechanisms may involve the effects of supraphysiological estradiol levelsPart ? Proteomic study of umbilical artery of ovarian hyperstimulation syndromeObjective:To investigate the molecular mechanism of cardiovascular dysfunction in ovarian hyperstimulation syndrome(OHSS)offspring at protein level.Materials and Methods:We collect umbilical arteries from women who diagnosed as severe OHSS and from spontaneously conceived women.Three samples from OHSS group and control group were performed iTRAQ-based proteomic study.Results from proteomics were verified and analyzed further with bio-informatics tools.Results:1640 proteins were identified from OHSS and SC umbilical arteries,and,40 differentially expressed proteins were selected for further analysis.The expression difference of SOD3 and GPX1 were verified using western blot.Bio-informatics analysis indicated that pathways involve glucose metabolism and oxidative stress were altered.Estradiol and progesterone were identified as activated upstream regulators.Conclusions:Proteomics showed altered protein profile in OHSS umbilical artery.Pathways involve glucose metabolism and oxidative stress were altered.Estradiol and progesterone were predicted as reason for protein differential expression.Part ? The effect of alternative splicing of mineralocorticoid receptor on blood pressure regulation in offspring of preeclampsia women:a mechanism studyObjective:To investigate the effect of Alternative splicing of mineralocorticoid receptor(MR)on blood pressure regulation inoffspring of preeclampsia womenMaterials and Methods:We collected umbilical vein from preeclampsia and normal pregnancies.Expression of splicing variants of MR and SCNNlA were evaluated.We further constructed plasmid contain MR with exon 5 deletion(Del E5 MR)or wild type MR.After transfection into hela cells,various ligand(Aldosterone,cortisone,11-dehydrocorticosterone and progesterone)were added to observe expression of SCNN1A.Results:The expression of Del E5 MR and SCNN1A were increased in preeclampsia umbilical vein,and,the expression of Del E5 MR was positively correlated with expression of SCNN1A.Three dimension prediction of protein conformation indicated abnormal ligand binding of Del E5 MR.In cell experiment,eortisone abnormally activated Del E5 MR and up-regulated SCNN1A while wild type MR was not activated.11-dehydrocorticosterone and progesterone was unable to activate wild type or Del E5 MR.Conclusions:Expression of Del E5 MR and SCNN1A were increased in offspring of preeclampsia.Cortisone can up-regulated SCNN1A via abnormally activate Del E5 MR,resulting increased risk of hypertension in offspring of preeclampsia.