Study On Bax、XIAP And Activin A In Pathogenesy Of IFGR

Fetal growth restriction(FGR) which drived from patho-reason of pregnancy is usually defined as a birth weight below the two standard or the10th percentile number of deviation of the average weight and the same sex with gestational age, or less than2500g born after37week. Actualiy it means the fetus growth did not reach the full potential of their genetic. Its incidence rang from3%-7%at home, and3%-10%in American, the morbidity is relevant with diagnostic criteria, the economic and social conditions, the perinatal mortality rate of FGR neonatorum is42.3%of the total number of Perinatal child mortality in China, and Its short-term and long-term neonatal complications were significantly increased. In recent years, the mother, placenta, umbilical cord, fetal pathology and other factors, leading to FGR which not only inhibited fetal growth and development, but also affectted long-term impact of childhood, adolescent physical and mental development, making the fetal origins of adult diseases such as cardiovascular disease, diabetes prevalence significantly increased. About40%FGR’s reason was unclear until now, which is called IFGR(idiopathic fetal growth restriction). Studies suggest that normal pregnancy is accompanied by placental trophoblast cell proliferation and apoptosis which make placental villi invade the uterine wall, apoptosis imbalance of maternal-fetal interface may affect the function of the placenta, thereby affecting the growth and development of the fetus, resulting in pathology of pregnancy. Apoptotic process is affectted by a series of gene regulation, Bcl-2family and IAP family (inhibitor of apoptosis proteins, IAPs,) which play an important role, and Bax(B-cell lymphoma associated x protein), XIAP(X-linked inhibitor of apoptosis protein) is one important member of the two families. Bax which is a Bcl-2homologous protein has a role to promote apoptosis. XIAP is able to inhibit caspase apoptosis pathway start-up phase and effector phase of apoptosis inhibitory protein. Bax, XIAP expression in placental tissue during pregnancy, through regulation of placental trophoblast cells proliferation and apoptosis during pregnancy, affect the fertilized egg implantation and placental growth and development. Activin A belongs to the transforming growth factor beta (TGF-β) superfamily. It can regulate reproductive endocrinology through a variety of hormones during pregnancy, induction of cell differentiation and embryonic development, and many other biological effects. A large number of studies have shown that activin A not only plays an important role in cell proliferation and apoptosis during carcinogenesis, but also can regulate trophoblast differentiation and blastocyst implantation and affect the pregnancy occurrence, development and fetal growth, activin A may play an important role in the incidence of IFGR. Activin A may related to intrauterine hypoxia, human early pregnancy cytotrophoblast cell in vitro can induced apoptosis by Activin A. Activin A may be correlated with apoptosis-related molecules, they combined to affect the development of the fetal placental unit which can resulting in FGR. The mechanism of Bax, XIAP and activin A in the incidence of fetal growth restriction is unclear, The study on correlation between BAX, XIAP, Activin A and IFGR.ObjectiveTo detect the expression of Bax、 XIAP in placenta and Activin A level in the maternal and cord serum,and explore their significance of IFGR.Methods1Study Object:From July2010to July2011,60singleton pregnant women being cesarean section in our hospital was randomly sampled selected in this study. The experimental group:30IFGR term pregnant women;The control group:30normal term pregnant women being cesarean section because of social factors. All subjects were informed consent in this study. FGR and IFGR was diagnosis according to Obstetrics and Gynecology which was the second edition and the chief editor was YouJi Feng.2Methods:2.1Placental Specimen Collection:All placenta samples were immediately cut the site which was lcm3after cesarean section, then cleaned by normal sodium and fixed in10%buffered formalin for24hours, followed by routine paraffin embeding, cutting (5μm),60℃broil to stay overnight,at last preservation in37℃environment.2.2Serum Specimen Collection:All maternal blood samples were collected less than two hours before cesarean section and the cord blood were immediately taken from the umbilical veins which were close to the placenta, then all the blood samples were injected to the non-anticoagulant test tube. After putting them at room temperature for1hour, centrifuging5minutes at3000rev./min, Separating the serum, located in the-80℃environment.2.3Experimental Methods:Bax and XIAP protein in placeta were detected by immunohistochemical method; Activin A in maternal and umbilical cord serum were detected by enzyme-linked immunosorbent assay (ELISA)3Statistical methods:SPSS13.0software is used for statistical analysis of data, all data using mean±standard deviation(x±s)are denoted. Comparison between the two mean used T test.Use Pearson correlation analysis used for determine the relationship of the factors,"a=0.05" was used for statistically significant level.Results1The comparison of clinical data:All the clinical data like the age, body weight, gestational weeks and gravidity of two groups of pregnant women found no statistically significant (P>0.05).The experimental group of neonatal with birth weight was lower than the control group (P<0.05). Neonatal complications in the experimental group was significantly higher than the control group(P<0.05).2The expression and correlation between Bax and XIAP in placenta.The expression of Bax and XIAP protein were found different levels in placenta of the two groups, which performance of yellow or brown staining (particles), mainly expressed in the cytoplasm and membrane of the placenta syncytiotrophoblast cells;In experimental group, Bax expressed in syncytiotrophoblast cells were (146.513±10.611)increased significantly compared to the control group(113.672±9.631),(P<0.05); XIAP expressed in syncytiotrophoblast cells were (114.562±5.167)decreased significantly compared to the control group(144.430±7.311),(P <0.05).In experimental group, the expression of XIAP in syncytiotrophoblast cells existed negetive corrolation with Bax (P<0.05); In control group, the expression of XIAP in syncytiotrophoblast cells exist no corrolation with Bax(y=0.034, P=0;856).3The expression and correlation between the Activin A level in maternal serum and the cord serum.The Activin A concentrations in maternal and cord serum of the experimental group were(102.659±16.467,57.752±13.498)μg/l both higher than the control group(75.927±10.519,29.870±5.992)μg/l(P<0.05).In control group and experimental group, the expression of Activin A in the maternal serum both found no correlation with the expression of Activin A in the cord serum(γ=0.330, P=0.075; γ=0.006, P=0.974).4The correlation between Activin A level in the serum and the expression of Bax and XIAP in the syncytiotrophoblast cells in placenta.In experimental group,the expression of Activin A in the maternal serum and cord serum both have positive correlation with the expression of Bax in the syncytiotrophoblast cells in placenta (γ=0.805, P=0.000; γ=0.603, P=0.000); the expression of Activin A in the maternal serum and cord serum both have negative correlation with the expression of XIAP in the syncytiotrophoblast cells in placenta(γ=-0.643, P=0.000;γ=-0.583, P=0.001);In control group, the expression of Activin A in the maternal serum and cord serum existed no correlation with the expression of Bax in the syncytiotrophoblast cells in placenta(γ=-0.145, P=0.445; γ=0.309, P=0.097); the expression of Activin A in the maternal blood and cord blood both existed no correlation with the expression of XIAP in the syncytiotrophoblast cells in placenta(γ=0.095, P=0.617; γ=-0.028, P=0.883).Conclusions1The increased Bax expression and decreased XIAP expression in placenta may important to IFGR.2The increased Activin A level in maternal and cord serum may participate in the development of IFGR.3In IFGR, the increased Activin A in serum may through the influence of Bax, XIAP expression and action to promote the occurrence of the disease.