| Objective: Fetal growth restrction (FGR) is one of the important perinatal complication, which affect growth not only in gastation, but also in childhood and puberty. In addition, FGR may increase the risk suffering the disease of cardiovascular system, nervous system and endocrine system. The pathogeny of FGR has been researched inland and overseas, but it was still not clear. Many studies indicated that placenta villi development and vessel vasodilation lessened in FGR, the same as the spire arterioles, so that urteroplacenta blood flow decreased, foetus became anoxic gradually, and fetal growth was retarded finally. The recent investigation discovered that the placentas growth is involved in many kinds of cytokine. Placenta growth factor(PLGF) is a kind of growth factor belong to the family of vascular endothelial growth factor(VEGF),which expresses on placenta primarily and regulates the development and activity of trophoblast and endothelial cells. In course of placenta forming, PLGF adjusts growth, proliferation, and differentiation of trophoblasts and endothelial cells. Appropriate PLGF level is good for fetus blood n ets developing, and thereby ensures the fetus demand for growth. This study search the action of PLGF in FGR by research expressing of PLGF in serum, placenta and decidua. Methods: The study involves clinical research and animal experiment.In clinical research, maternal antepartum blood,umbilical vein blood, placenta and decidua were collected before Caesarean birth and once after operation from the fifty pregnant woman in Department of Obstetrics and Gynecology of our hospital, which including normal pregnancy twenty cases, FGR and hypertension disorder complicating pregnancy(HDCP) respective fifteen cases. Serum PLGF concentration of maternal antepartum blood and umbilical vein blood were measured using a enzyme linked immunosorbent assay(ELISA). The placenta and decidua tissue were detected by HE stain, and the expression of PLGF protein and PLGF mRNA were analysed by immunohistochemistry and in situ hybridization. In addition, PLGF mRNA of the tissue were measured by semiquantitative RT-PCR. In animal experiment, the FGR rat animal model was established successfully by interdicting the ovary artery of pregnant rats.Adult healthy SD female rats were randomly divided into three groups: sham operation control group(rat normal control, RNC), homogeneity contrast group(rat homogeneity contrast,RHC),variant contrast group(rat variant contrast,RVC), in which there were all ten rats. The rats were kept in standard condition after copulation.The pregnant rats undergone the operation in 15 days of pregnancy and Caesarean birth in 21days of pregnancy. Just after Caesarean birth,the fetuses avoirdupois and weight of placentas, brains, hearts, livers, lungs and kidneys of every groups were compared. The placenta tissues were collected synchronously, in which PLGF protein and PLGF mRNA were analysed by immunohistochemistry, in situ hybridizationand and semiquantitative RT-PCR. Results: In clinical research, the ELISA results of maternal blood and umbilical blood in the normal pregnancy group showed higher than FGR and HDCP group distinctly(P<0.01). In HE stain slice of the placentas, villi developing well, blood vessels expanding distinctly, there were less interstitial cells and more syncytiotrophoblast(STB) nodes and cell bridges in normal pregnancy group than two other groups. In the decidua, there were some trophocytes and spire arterioles. Whereas the villi developing and blood vessels expanding worse, there were less STB nodes and cell bridges in FGR and HDCP groups, but more interstitial cells than normal pregnancy group. The trophoblasts and spire arterioles were rare in decidua tissue of complication groups. PLGF protein and mRNA expressed in STBs mainly, and in interstitial cells, endothelium cell, decidua cell,and trophoblasts rarely. In FGR and HDCP groups, the expression level was lower than normal group ( P<0.05 ) and expressiong position was similar, however the former was indiscriminate between FGR group and HDCP group(P>0.05). In animal experiment, avoirdupois increment of pregnant rats and the fetus death rates had no difference among the groups(P>0.05). In RNC group and normal side of RHC group(RHn), the weight of new-laid rats and their placentas, brains, hearts, livers, lungs and kidneys were all higher than RVC group and FGR side of RHC group(RHf)(P<0.01), whenas they were not different between RNC and RHn,either between RVC and RHf(P>0.05). The rats placentapathology indicated that in RNC and RHn the decidua area was narrow, which was commonly made up of fibrin component. Present at the basal area were network formed by many trophoblast giant cells and a little hepatin cells, where maternal blood passed before came onto labyrinth area. But in RVC and RHf, ducidua area sweeled and thickened, while eukocyte infiltrating. Trophoblast giant cells hyperplasia in the thickened basal area. Intervascular membrane thickeded,and part of region was swell, metamorphic and necrosis in labyrinth area, in which trophoblasts hyperplasia and hypertrophy. By immunohistochemistry, in situ hybridization and semiquantitative RT-PCR, the results suggested that expression level of PLGF protein and mRNA were higher in RNC and RHn than in RVC and RHf(P<0.05), wheras they were similar between RNC and RHn, either RVC and RHf(P>0.05). Conclusions: (1)In normal pregnancy, STBs synthesize and secrete PLGF principally, and villi interstitial cells, endothelium cells and decidua cells do that little. The study suggested that PLGF expression level was reduced in FGR, which happened in transcription process. (2) When fetal growth restricted, serum PLGF concentration of maternal antepartum blood and umbilical vein blood was lower significantly than normal pregnancy, so that we can evaluate the placenta function and fetus status by inspecting the serum PLGF level, which may supervise obstetric clinical practice.(3)Basing anatomic character of rats that uterine artery is an embranchment of ovary artery, by clamping the pregnant rats ovary artery blood flow temporarily we construct a FGR animal model successfully, which showed that weight of new-laid rats and their placentas, brains, hearts, livers, lungs and kidneys descended.The model is facility and being repeated simply, and can carry out contrast study.It overcomed the shortcoming of interdicting-celiac-artery FGR model which could not make control, and solved the problem in interdicting-uterine-artery FGR model which is carrying and populariing hardly, so that it is scientific and applied ,and provides a technique to research FGR.(4)By this animal model, we made a anoxic status in placenta, which can downgrade the PLGF level.The consult is consistent with the vitro study and proved that anoxia is one of the most important reason which could adjust PLGF synthesizing and secreting.It suggested that PLGF expresion down-regulation due to ischemia may be one of the important role in FGR pathogenesis. Because of PLGF reduced,the activity of trophoblasts proliferating weakened, either of the endothelium cells. Subsequently angiogenesis may be Inhibited so that the development of villi and capillary network of placenta are blocked, which reduced the perfusion of placenta, and disturbed the development of the fetus.We could attempt regulating the role of PLGF in trophoblasts and endothelium cells, which may be improve the blood perfusion in placenta and status of fetus in FGR.
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