The Study Of GCMa、syncytin In Pathogenesy Of IFGR

Fetal growth restriction (FGR) refers to the fetus did not achieve its genetic growth potential, the morbidity of FGR is up to10%around the world. The reason of40%pregnancies complicate the FGR is unclear, so it named Idiopathic Fetal Growth Restriction (IFGR). The perinatal mortality rate in FGR is4to10times higher than normally grown neonatal and about5%-10%of pregnancy with FGR will result in stillbirth or neonatal death. It is reported that there are more long-term complications in the infants who suffer from FGR, including Nervous system dysplasia and growth retardation and these kinds of neonatal are easy to affect cardiovascular system diseases and diabetes. So it is importantly to find the basic pathogenesis of FGR so that we can make the therapeutic measures. The etiology of FGR is complex and multifactorial, however, there are a lot of factors negatively influence the fetal growth but we still poorly knew the detail pathogenesis. The reasons include maternal factors, for example malnutrition, chronic hypertension, preeclampsia. In addition, placentation defect and fetal factors such as chromosome abnormality and congenital anomalies are also influence birth weight.The reason of placentation defect results in placental insufficiency so that it influences the exchange of nutrition between mother and fetus and it can lead to metabolic waste transport disorder. The aspect of placental insufficiency is the reduction in blood flow in uterine artery. Additionally the increasing of uterine artery resistance is the common reason of FGR, because the high resistance reduces the uteroplacental perfusion. Perfusion reduction results in effective oxygen content decreased and the exchange of nutrition decreased too. This important substance transports through the placenta. So placental insufficiency directly effect on fetal growth in utero. The abnormalities of uterine artery circulation perfusion can cause placenta anaerobic and local anemia and reperfusion events lead to oxidative stress response, Superoxide generation and oxygen free radicals can cause damage to the structure and function of placenta. In the early of pregnancy (7-9days), the early invasive syncytiotrophoblast contact uterine tissues then the extravillous trophoblast invade the uterine decidua and the myometrium enlarge the vessel lumen it named "Vascular recasting". At this time, uteroplacental filling is quantity increased. Normal placenta villus structure contains outer syncytiotrophoblast (ST) and inner cytotrophoblast (CT). The former constantly was formed by the fusion of CT in order to secrete the hormone and play the role of exchanging the nutrition. Not only CT can fuse to ST, but also it can form trophoblast cell column then it can generate the extravillous trophoblast (EVT) that promote the placentation.Syncytin belongs to human endogenous retroviruses (HERV) family, it is the envelope protein which is coded by HERV-W gene. Its function is promoting the membrane’s fusion. It can induce the CT to ST. It has an important role in maintain the formation and function of normal placenta. Glial cells missing (GCM) is transcription factor with a conserved DNA-binding domain. In the development of placenta, there are numerous transcription factors in the differentiation and fusion of trophoblast, GCMa is the necessary transcription factor because it can regulate many related gene’s expression which take part in cell fusion. The activity of GCMa expression can be through the cAMP path, GCMa gene identify the two upstream sites of syncytin-5’long terminal repeat (5’LTR) in order to enhance the expression of syncytin gene. Placenta growth factor (PLGF) was discovered in vascular endothelial growth factor (VEGF) family. Due to it was detected in placenta tissue by cDNA clone, so it named placenta growth factor and this imply PLGF is useful in trophoblast invading the uterine decidua. In addition, some scholars think that GCMa low expression can reduce PLGF promoter activity lead to the PLGF down-regulate. ObjectiveTo detect the expression of GCMa and syncytin in normal placenta tissue and IFGR placenta tissue by immunohistochemical and RT-PCR in order to discuss the function of these two factors in pathogeny of FGR. It can provide the clues of deep etiology in IFGR and the theoretical basis of intervening measure.Methods1Study ObjectEighty pregnant women who have delicery in the third affiliated hospital of zhengzhou university from2010.12-2012.03were object.40pregnant women with IFGR who delivered through cesarean section are experimental group and40normal pregnant women who delivered at term through cesarean section because of social factors are control group. There is no statistical significance in pregnant women age, progestation weight, gestational weeks, pregnant times (P>0.05). but weight of newborn have statistical significance (P<0.05). The diagnosis of FGR and IFGR according to Obstetrics and Gynecology which was the seventh edition.2Methods2.1Placental tissue specimen collection:placenta tissue specimens were obtained at regular, full-term deliveries. The tissue specimens were frozen for immunohistochemistry and RT-PCR.5-μm-thick tissue sections were obtained from each tissue block which underwent formalin-fixed, paraffin-embedded.2.2detection methods:The expression of syncytin and GCMa was detected in40placenta specimens with IFGR (Idiopathic Fetal Growth Restriction) and40normal placenta tissues collected in the same period by immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR).3Statistical methodsAn a of0.05was used for all statistical tests. Analyses were done using SPSS sof-tware. Results1The comparison of clinical dataThere is no statistical significance in pregnant women age, progestation weight, gestational weeks, pregnant times (P>0.05). The weight of experimental group(2198.10±149.59)g was lower than the control group(3675.88±270.61)g (P <0.05).2The expression and correlation of GCMa and syncytin protein in control group and experimental groupThe protein of GCMa and syncytin positively express in syncytiotrophoblast, with the measure of gray value, the expression of GCMa in experimental group (120.81±4.42)lower than control group (160.45±7.83); the expression of syncytin in experimental group (110.73±7.95) lower than control group (148.49±5.20).Positive relation was found in the expression of syncytin and GCMa in IFGR tissue (r=0.480, P=0.002).3The expression and correlation of GCMa and syncytin mRNA in control group and experimental groupWith the measure of gray value to detect the expression of GCMa and syncytin mRNA, the expression of GCMa in experimental group (0.11±0.01) lower than control group (0.43±0.02); the expression of syncytin in experimental group (0.13±0.01) lower than control group (0.55±0.02). Positive relation was found in the expression of syncytin and GCMa in IFGR tissue (r=0.410, P=0.009).Conclusions1Both of the expression of GCMa and syncytin were high in control groups of placenta tissue but lower in IFGR placenta tissue, which may be the reason of their synergistic effect.2The low level of GCMa mRNA and syncytin mRNA in IFGR placenta tissue suggests that their functional defect on the transcriptional level。...