| Background:Sialic acids(Sia)are a diverse family of nine-carbon sugar neuraminic acid as the basic structure of derivatives,widely distributing in nature and playing important roles in lots of vital physiological processes.N-acetylneuraminic acid(Neu5Ac),N-glycolylneuraminic acid(Neu5Gc)and 2-keto-3-deoxy-D-glycero-D-galactonononic acid(KDN)are sialic acid's main subtypes,the first two are the most common form in mammals,but Neu5Gc is devoid in the human.Biomedical research of Sia is focus on infection diseases,tumor,coronary disease,development of nervous system and neurodevelopmental delay disease.Sia is expressed in all body tissues and body fluids including blood,saliva,gastric juice,brain spinal fluid in human.As Sia expression levels vary with health and disease state of indivadual,therefore Sia can be used as a biomarker for diseases diagnosis in the clinic.In human productive medcine,Sias expression levels are gradually change during pregnancy.For instance,Sia concentration in saliva,serum and amniotic fluid of healthy pregnant women increases constantly for fetal development during pregnancy.Since Sia is an enssential nutrient in human milk and brain gangliosides and sialylated glyproteins,ectogenic Sia plays an building block role for early infants' growth and development.Our hypothesis is that the changes of different form Sia levels in blood and tissues during pregnancy and labor are closely associated with maternal-fetal's Sia metabolism,brain Sia accumulation of fetus,complications of pregnant women and pregnant outcomes.Assisted reproductive technology(ART)is a method to complete reproductive process by using medical auxiliary means in the process of one or all links,involving lots of non natural conception process.There is a big difference with natural pregnancy.ART has been used in clinic nearly forty years,it benefits to patients with infertility,but its adverse outcomes for mother and newborns are increased,since the use of ART has increased substantially in China.Sia is an important molecule involving in the process of human reproductive process,but the role of Sia in ART women has not been studied at present.We compared pregnancy outcomes between ART and natural pregnancy,analyzed the level of Sia in different blood samples and tissues to explore the underlying mechamisim of the relationship of Sia content and ART pregnancy outcome,these studies provide unique opportunities to improve perinatal outcome of ART women and natural pregnancy women.Objective:We tested the hypothesis that changes of different form Sia levels in serum,plasma,erythrocyte membrane,umbilical cords and placentas during pregnancy and labor are closely associated with maternal-fetal's Sia metabolism,brain Sia accumulation of fetus,complications of pregnant women and pregnant outcome.Methods:One hundred and nineteen pregnancy women including ART and natural pregnancy in Chenggong Hospital affiliated to Xiamen University and Fuzhou Maternity and Child Health Care Hospital were involved in this study.There were 60 ART and 59 natural pregnant women respectively,including 21 pregnant women of gestational diabetes mellitus.Sia levels of blood samples,umbilical cords and placentas were quantified by sensitive LC-MS/MS.Results:Pregnancy women of ART(1)Age,living conditions and the incidence of adverse pregnancy outcomes such as pregnancy complications,premature birth,low birth weight,multiple pregnancy rate were significantly higher than control group(P<0.01)5 neonatal length was significantly shorter than control group(P<0.01);(2)The conjugated KDN of cord blood plasma was significantly lower than that of control group(P<0.05),total Sia content of serum(34.33±2.05?mol/g protein)and in cord blood serum(24.07±2.76?mol/g protein)were significantly higher than that of control group(P<0.05);(3)The total Sia content of erythrocyte membrane in pregnant women,cord blood and infants,umbilical cords,placentas were 574.63±32.93?mol/g protein,302.20±30.10?mol/g protein,44.83± 3.41?mol/g protein,33.12±10.07?mol/g protein,and 229.99±19.83?mol/g protein respectively.Those infants' Sia in erythrocyte membrane was significantly higher than control group(P<0.01),while umbilical cords and placentas' Sia were significantly lower than control group(P<0.01);(4)Neu5Gc was not detected in any samples,and the main form of Sia is conjugated Neu5Ac.The proportion of free KDN in total KDN was higher than control group.Pregnant women of gestational diabetes mellitus(GDM)(1)Total Sia content of cord blood plasma(41.42±19.05?mol/g protein)was significantly higher than pregnancy women who did not have GDM(P<0.05);(2)Neu5Gc was not detected in any samples,and the main form of Sia is conjugated Neu5Ac.The proportion of freeKDN in total KDN was higher in GDM women than without GDM pregnant women;(3)There was positive correlation between total Sia content of serum in GDM women and the neonates blood glucose(P<0.05).All pregnant women including ART,GDM and others(1)There were positive correlation between total Sia content of serum,erythrocyte membrane,infants'erythrocyte membrane and pregnancy complications except GDM(P<0.05),negative correlation between total Sia content in umbilical cords,placentas and pregnancy complications except GDM(P<0.01);(2)The higher total Sia content of serum,cord blood serum and infants' erythrocyte membrane was,the higher incidence of adverse fetal outcomes was(P<0.05);(3)There was negative correlation between total Sia content of serum and new born weight(P<0.01),positive correlation between totalSia content in placentas and new born weight(P<0.05);(4)Total Sia content of serum,erythrocyte membrane,cord blood serum,plasma,erythrocyte membrane and umbilical cords,placentas,infants' erythrocyte membrane among screened healthy mothers and infants were 23.60±16.97?mol/g protein,404.64±220.24?mol/g protein,14.22±2.72?mol/g protein,0.04±0.02?mol/g protein,237.77±58.14 ?mol/g protein,137.27±112.77?mol/g protein,459.69±297.90?mol/g protein,27.73±9.65?mol/g protein respectively,and Neu5Gc was not detected in any samples.Conclusion:Total Sia concentration of ART pregnancy women was significantly higher than that of natural pregnancy in serum,cord blood serum,infants' erythrocyte membrane,and lower than that of natural pregnancy in tissues of umbilical cords and placentas respectively.Total plasmatic Sia level of GDM pregnancy women was significantly higher than that of others.The higher total Sia content of maternal serum was,the higher neonates blood glucose was,the lower newborn body weight was.the higher placentas' sialic acid content was,the higher newborn body weight was.There was negative correlation between total Sia content of maternal serum,infants'erythrocyte membrane,umbilical cord,placental tissue and adverse maternal-fetal pregnancy outcomes. |
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