Analysis of gene expression in placenta of severe preeclampsia / 대한주산의학회잡지

OBJECTIVE: This study was designed to detect genes specifically expressed in severe preeclamptic placentas. METHODS: Placenta tissues were collected immediately after delivery from 5 preeclamptic patients and 5 normal pregnant women. Total RNAs of each placenta were extracted and hybridized for a cDNA microarray. Of the microarray data, four up-regulated genes (DSCR4, GPA, PCDHGB1, Hemogen) and four down-regulated genes (IL1R2, MGST1, GAS1 GREB1) were selected and reverse transcriptase-polymerase chain reaction was used to confirm the results of cDNA microarray. RESULTS: The expression fold for each up-regulated gene was 2.2 times for DSCR4, 2.7 times for PCDHGB1, 3.5 times for Hemogen, 5.2 times for GPA on the cDNA microarray. The expression fold for each down-regulated gene was 3.3 times for IL1R2, 4.2 times for MGST1, 4.9 times for GAS1 and 2.3 times for GREB1 on the cDNA microarray. The expression fold for each up- regulated gene was 5.21 times for DSCR4, 3.01 times for PCDHGB1, and 4,53 times for Hemogen and 2.2 times for GPA on RT-PCR. The expression fold for each down-regulated gene was 2.7 times for IL1R2, 2.22 times for MGST1, 2.53 times for GAS1 and 1.83 times for GREB1 on the RT-PCR. CONCLUSION: DSCR4, PCDHGB1, Hemogen and GPA as the up-regulated genes and IL1R2, MGST1, GAS1 and GREB1 as the down-regulated genes, which were found and selected by the cDNA microarray, might be considered to be novel biomarkers for preeclampsia.

Differential gene expression of transglutaminase 2 in term pregnancy with and without labor / 대한산부인과학회지

OBJECTIVE: Our purpose was to investigate transglutaminase 2 (TGM2) mRNA and protein expressions in term placentas and fetal membranes delivered with labor compared to no labor. METHODS: Samples were obtained from five cases delivered with labor and five cases delivered without labor after 38 weeks of gestation. Each sample was collected from amnion, chorion, central and peripheral portion of the basal plate of placenta. Real time polymerase chain reaction (RT-PCR) was done to analyze mRNA expression of TGM2. Western blot was done and TGM2 protein level was detected. Mann-Whitney U test was used for statistic analysis. RESULTS: In labor group, TGM2 mRNA expressions were decreased compared to no labor group in 3 sampling sites except chorion (0.66+/-0.10 vs 1.29+/-0.12 in peripheral placenta, 0.67+/-0.23 vs 1.02+/-0.02 in central placenta, 0.70+/-0.16 vs 1.04+/-0.05 in amnion in contrast with 1.62+/-0.64 vs 1.56+/-0.21 in chorion). TGM2 protein expressions of four differential portions were decreased in all labor groups (1.05+/-0.35 vs 1.27+/-0.19 in peripheral placenta, 0.69+/-0.84 vs 0.84+/-0.31 in central placenta, 0.33+/-0.15 vs 0.39+/-0.33 in amnion, 0.96+/-0.18 vs 1.77+/-0.61 in chorion). CONCLUSIONS: This result suggests that TGM2 might involve in labor progress of term pregnancy.

Differential Gene Expression in Placenta of Term Pregnant Women with and without Labor using cDNA Microarray / 대한주산의학회잡지

OBJECTIVE:cDNA microarray technology was used to comprehensively analyze the gene expression in the placenta of term women with labor compared to without labor. METHODS:Placental tissue was obtained from patients in spontaneous labor (n=5) and those not in labor (n=5) during Cesarean section of full term pregnancy. mRNA levels were examined through cDNA microarray using Agilent GeneSpringGX 7.3 (Agilent technology, USA). SPSS 11.0 was used for statistical analysis. RESULTS:Among total 38,467 genes, 2,374 genes were detected to be up-regulated in labor samples, while 12 genes were down-regulated. 40 genes of them were identified as significantly up-regulated in levels of expression (up-regulated > or =5.0 fold, p<0.05). According to gene ontology analysis, they are associated with variable cell biologic functions including apoptosis, signal transduction, metabolic process, immune response, and transcription, etc. CONCLUSION:This study suggests that our results could provide interesting clues to understanding the initiation and the process of normal labor and might lead to further studies in a more targeted fashion.

Expression of Tissue Tissue-transglutaminase-2 (TGM2) and Cyclo-oxygenase (COX) in the Fetal Membrane of Preterm Birth / 대한주산의학회잡지

BACKGROUND: Preterm labor accounts for one third of preterm deliveries. However, the causes and the mechanism of preterm labor are still under investigation. The purpose of this study was to investigate the changes of tissue transglutaminase 2 (TGM2) and cyclo-oxigenase I,II in the fetal membrane of patients with preterm birth compared with patients with term delivery. METHODS: Fetal membrane were obtained from women with preterm birth due to preterm labor (n=3) and from the women with term delivery (n=3) after each vaginal birth. The expression of TGM2, COX I & II were assessed by RT-PCR and immunoblotting analysis of the amnion and chorion. Nonparametric statistics were used for analysis. RESULTS: In the amnion in patients with preterm delivery, the expression of TGM2, COX I and COX II mRNA were increased by 2.3-fold, 2.7-fold, 1.3-fold, respectively, compared to term delivery with labor. The protein expression of TGM2 and COX I in these patients was increased in 1.9-fold and 2.1-fold but COX II protein expression showed no significant change, compared to term delivery with labor. In the chorion in patients with preterm delivery, the expression of TGM2, COX I and COX II mRNA showed no significant change, compared to term delivery with labor, but the protein concentration was significantly increased in 14.6-fold, 1.4-fold and 1.3-fold respectively, compared to term delivery with labor. CONCLUSION: This study shows that TMG2 and COX I are expressed more in the fetal membrane at preterm delivery caused by preterm labor, compared to term delivery with labor. These data suggests that the mechanism of preterm labor might be different form term labor.

Analysis of Gene Expression in the Human Chorion of Preterm Labor Using cDNA Microarray / 대한주산의학회잡지

OBJECTIVE: We used a genome-wide approach to identify differentially expressed genes in patients with preterm delivery caused by preterm labor to improve the understanding of underlying molecular mechanism. METHODS: RNA was isolated from the chorions of patients with preterm delivery caused by preterm labor with intact membranes and term vaginal delivery. cDNA microarray experiments were used to identify differentially expressed genes, and reverse transcriptase-polymerase chain reaction was used in follow-up experiment. RESULTS: cDNA microarray experiments identified significantly increased expression of 104 genes and decreased expression of 102 genes in the preterm cases. 18 genes showed more than 1.5-fold increased expressions in the chorions of patients with preterm delivery by preterm labor than those with term vaginal delivery. In preterm delivery, up-regulated genes were associated with cell adhesion, cell cycle regulation, development, transport, morphogenesis, muscle contraction, signal transduction, and transcription. 15 genes showed more than 1.5-fold decreased expressions in chorions of patients delivered preterm by preterm labor than delivered term by labor. In preterm delivery, down-regulated genes were associated with cell differentiation, development, metabolism, morphogenesis, RNA processing, signal transduction, transcription, and transport. CONCLUSION: This study suggests cDNA microarray technique might provide insights into the molecular basis of preterm delivery caused by preterm labor.

Search for Differentially Expressed Genes in Preterm Human Placentae and Their Membranes by Annealing Control Primer System / 대한주산의학회잡지

OBJECTIVE: The aim of this study was to investigate the gene expression profiles using GeneFishingTM kit in human placentae and their membranes delivered at preterm caused by preterm labor. METHODS: Specimens were obtained from placenta, chorion, and amnion delivered at preterm and term, respectively. Total RNAs were isolated from each specimen. Thereafter, the profiles of expression genes between preterm and term specimens were compared using a new and accurate reverse transcription-polymerase chain reaction (RT-PCR) that involves annealing control primers (ACPs) to identify the genes expressed differentially and screened by basic local alignment search tool (BLAST) search. RESULTS: Using 20 ACPs, 13 differentially expressed genes (DEGs) were identified and sequenced. 7 of them were expressed up-regulation, while 6 were expressed down-regulation in preterm deliveries. A BLAST searches revealed that 11 were known genes and 2 were unknown genes. Among known genes, up-regulated genes were insulin-like growth factor II associated protein, vigilin, acyl-Coenzyme A dehydrogenase, tissue inhibitor of metalloproteinase 1 (TIMP1), ribosomal protein S26 (RPS26), follistatin-like 1 (FSTL1) and down-regulated genes were two mitochondrial DNAs, ribosomal protein S28 (RPS28), transglutaminase 2 (TGM2), heparin sulfate proteoglycan (HSPG, perlecan). CONCLUSION: This study shows that the ACP system is a good method for the identification of preterm-related genes. Furthermore, this study suggests that further analysis of the differentially expressed genes in preterm we have identified should provide insights into the molecular basis of preterm delivery caused by preterm labor.

Association of the polymorphisms in CYP1A1 and CYP1A2 genes with preterm premature rupture of membranes / 대한산부인과학회잡지

OBJECTIVE: Preterm delivery (PTD) is the leading cause of perinatal mortality and morbidity. However, its etiology and pathogenesis remain unknown in most cases. Recently, some research put forth the hypothesis that PTD results, at least in part, from a genetic predisposition. This study was undertaken to elucidate whether polymorphisms of cytochrome 450 (CYP) 1A1 and 1A2 are associated with PTD caused by preterm premature rupture of membrane (PPROM) in Korean pregnant women. METHODS: From August 2002 to October 2003, in the affiliated hospitals in the Catholic University of Korea, we have collected the samples from the 264 women who delivered after 37 weeks and from 26 women who delivered following spontaneously ruptured membranes before 37 weeks. RESULTS: There was no significant difference in the genotype frequency as well as in the allelic frequency of CYP1A1*m2 in PPROM group compared with the control group (54% vs. 66%, P=0.224; 0.29 vs. 0.40, P=0.111, respectively). The genotype frequency of CYP1A2*C was significantly higher in PPROM group than in the control group (69% vs. 49%, P=0.047). However, the allelic frequency of CYP1A2*C was not significantly higher in PPROM group than in the control group (0.4 vs. 0.275, P=0.45). CONCLUSION: These results suggest that CYP1A2*C may be, at least in part, associated with PPROM.

ATP and Adenosine Induce Growth Inhibition and Apoptosis in Human Trophoblast-like (TL) Cell Line / 대한산부인과학회잡지

BACKGROUND: Although nucleotides -like Adenosine Triphosphate (ATP) and its derivatives Adenosine, were known to induce growth inhibition and apoptosis in diverse cell lines, little is known about their effects on trophoblast. OBJECTIVE: To elucidate the effects of extracellular ATP and adenosine on trophoblast cell growth and to delineate if apoptosis is involved in this mechanism. MATERIALS AND METHODS: We used TL cell line, derived from human term placenta. The cells were cultured for 24, 48, and 72 hours after being treated with ATP and adenosine, each. Also, cell growth according to different concentrations of ATP and adenosine was evaluated. To test whether apoptosis was induced by each nucleotide, DNA fragmentation and nuclear condensation by Hoechst 33258 stain and P53 protein expression were evaluated. RESULTS: Cell growth was inhibited by ATP and adenosine in time and dose-dependent manner. Furthermore, the growth inhibitory effect of adenosine was stronger than ATP, whereas signs of DNA fragmentation and nuclear condensation were observed in ATP treated cells, but not in adenosine treated ones. CONCLUSION: Our results shows that ATP and adenosine exert inhibitory effect on growth in TL cell line. These findings suggest that pathological production of ATP or its metabolites, adenosine, may lead to a pathologic status such as preeclampsia or intrauterine growth restriction.

Influence of Hypoxia on Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor in Cultured Human Trophoblast / 대한산부인과학회잡지

OBJECTIVE: To investigate whether the hypoxic condition influences on the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) mRNA in the cultured human trophoblast. METHODS: Trophoblasts were isolated from the normal placenta in early pregnancy (6-10 weeks in gestation). Isolated trophoblasts were cultured under normoxic (5% CO2, 95% humid air in incubator) and hypoxic (MERCK, 1% O2, 99% CO2) conditions for 24, 48 and 72 hours, respectively. Total RNA was extracted from the cultured trophoblasts in each culture condition. The expressions of VEGF and bFGF mRNA were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analysis. RESULTS: The expression of VEGF189 mRNA was significantly increased in the hypoxic condition compared to the normoxic condition and control after 24 hours (p<0.05, p<0.05, respectively). The expression of VEGF206 mRNA was also significantly increased in the hypoxic condition compared to the normoxic condition and control after 48 hours (p<0.05, p<0.05, respectively). However, there was no significant difference between the normoxic and hypoxic conditions in the expression of VEGF121 and VEGF165 mRNA. The expression of bFGF mRNA was significantly increased in the hypoxic condition compared to the normoxic condition and control at 24 hours and 48 hours (p<0.05, p<0.05, respectively). bFGF mRNA was more expressed than VEGF mRNA in the hypoxic condition. CONCLUSION: These findings suggest that the hypoxic condition may stimulates the expression of bFGF and VEGF mRNA, and besides bFGF may be a more potent inducer of angiogenesis rather than VEGF in early human gestation.

Role of Cyclooxygense-2 in Lipopolysacharide induced Matrix Metalloproteinase-2 and -9 expressions in human trophoblast (TL) cell line / 대한산부인과학회잡지

OBJECTIVE: To evaluate whether lipopolysaccharide (LPS) modulates the expression of cyclooxy- genase-2 (COX-2) and also whether COX-2 is involved in the LPS induced matrix metalloproteinase-2 (MMP-2) and MMP-9 activation in human trophoblastic (TL) cell line. METHODS: We used the TL (trophoblast-like) cells and evaluated the effect of LPS on expression of COX-2 mRNA and protein and on activities of MMP-2 and MMP-9. Also, we pretreated cell line with LPS and NS398, a COX-2 inhibitor, and compared MMPs activities with LPS only group. In the present study, COX-2 was analyzed by RT-PCR and western blot analysis and gelatin zymography was done for the evaluation of gelatinase activities of MMP-2 and MMP-9. RESULTS: The mRNA and protein expressions of COX-2 were increased by LPS in time- and dose-dependant fashions. COX-2 mRNA expression began to rise from 1 hour of LPS treatment and was increased steadily thereafter. COX-2 protein expression was detected from 1 hour of LPS treatment, but maximally increased by the 3 hours of treatment. LPS also increased MMP-2 and MMP-9 activities in time and dose dependant fashions. Especially, active form of MMP-9 was observed in the high concentration of LPS (>50 microgram/ml). When adding COX-2 inhibitor (NS398) to LPS pretreated cell line, the MMPs activities increased in two or three fold compared to LPS only group. CONCLUSION: Our results suggested that LPS induces expression COX-2 and up-regulates activities of MMP-2 and MMP-9 in trophoblastic cell, but COX-2 although involved in LPS mediated MMP-2 and MMP-9 activation, may act through a different pathway than the commonly known prostaglandin metabolites mediated one.

Role of nitric oxide and interleukin-1beta on expression of matrix metalloproteinase-2 in TL cell line / 대한산부인과학회잡지

OBJECTIVE: We studied to investigate whether nitric oxide (NO) and IL-1beta modulate MMP-2 and MMP-9 using TL cell line obtained from the normal term placenta. METHODS: After culturing TL cell line for 4 hours, we treated 0.1 mM of SNAP (NO donor) and 50 ng/ml of IL-1beta for 0, 1, 3, 6, and 12 hours, for investigating changes from time. We treated SNAP of 0, 0.01, 0.1, and 0.5 mM for 12 hours and IL-1beta of 0, 1, 10, and 50 ng/ml, for investigating changes from concentration. After extraction of total RNA, we performed reverse transcriptase-polymerase chain reaction (RT-PCR), gelatine zymography and Western blot analysis, for investigating expression of MMP-2 and MMP-9. RESULTS: MMP-9 was not observed in TL cell line. The expressions of MMP-2 mRNA and protein were gradually increased according to the culture time in SNAP treated group. The expressions of MMP-2 mRNA and protein were gradually increased according to the culture time in IL-1beta treated group. The expression of MMP-2 protein was not more increase in SNAP/IL-1beta-treated group than in IL-1beta treated group. The expression of MMP-2 protein was more reduced in SNAP/hemoglobin treated group than in SNAP treated group. MMP-2 protein activity was only increase in SNAP treated group. CONCLUSION: These results indicate that NO, rather than IL-1beta, upregulates the MMP-2 in TL cell line and furthermore may influence in the invasive process of trophoblasts.

Influence of Hepatocyte Growth Factor on Matrix Metalloproteinase Expression in HT cell line / 대한산부인과학회잡지

OBJECTIVE: This study was performed to investigate the influence of hepatocyte growth factor (HGF) on matrix metalloproteinase (MMP), which are related in the lysis process of tissue during the invasion of trophoblasts. METHOD: HT cell line was treated with recombinant HGF (rHGF) of different concentration (0, 10, 50 and 100 ng/mL) and was cultured for 24 hours to check the changes in the expression of MMP-2 and MMP-9. Also, HT cell line was treated with recombinant HGF 50 ng/mL and was cultured for 24, 36, 48, and 72 hours to check the changes in the expression of MMPs according to the different time span. Total RNA were extracted from each cultured sample and RT-PCR and Western blotting were used to analyze the expression of MMP-2 and MMP-9. RESULTS: MMP-2 mRNA expression with treated rHGF showed increase of 2, 2.5 and 2.2 times with the increase of concentration level of 10, 50 and 100 ng/mL accordingly, while MMP-2 protein expression were increased 1.4 and 1.5 times in 50 ng/mL and 100 ng/mL of rHGF respectively compared with that of normal control. MMP-9 mRNA showed no significant changes in its expression with all different levels of concentration, while MMP-9 protein showed 1.5 times increase with 10 ng/mL rHGF but 0.4 times decrease with 100 ng/mL. MMP-2 mRNA expression treated with recombinat HGF were increased 1.6 times with 24 hour culture and 2.3 times with 36 hour culture. MMP-2 protein showed 1.9 times increase only for the case of 24 hour culture. MMP-9 mRNA expression of recombinant HGF-treated groups was decreased 0.7 times compared with that of control group in 36 hours. MMP-9 protein expression were increased by 1.2, 1.6 and 1.9 times as culture time increase to 36, 48, and 72 hours accordingly, compared with that of normal control. CONCLUSION: This result suggests that the HGF might partially regulate the invasion of trophoblasts through MMP-2 and MMP-9.

Influence of Hepatocyte Growth Factor on Matrix Metalloproteinase Expression in HT cell line / 대한산부인과학회잡지

OBJECTIVE: This study was performed to investigate the influence of hepatocyte growth factor (HGF) on matrix metalloproteinase (MMP), which are related in the lysis process of tissue during the invasion of trophoblasts. METHOD: HT cell line was treated with recombinant HGF (rHGF) of different concentration (0, 10, 50 and 100 ng/mL) and was cultured for 24 hours to check the changes in the expression of MMP-2 and MMP-9. Also, HT cell line was treated with recombinant HGF 50 ng/mL and was cultured for 24, 36, 48, and 72 hours to check the changes in the expression of MMPs according to the different time span. Total RNA were extracted from each cultured sample and RT-PCR and Western blotting were used to analyze the expression of MMP-2 and MMP-9. RESULTS: MMP-2 mRNA expression with treated rHGF showed increase of 2, 2.5 and 2.2 times with the increase of concentration level of 10, 50 and 100 ng/mL accordingly, while MMP-2 protein expression were increased 1.4 and 1.5 times in 50 ng/mL and 100 ng/mL of rHGF respectively compared with that of normal control. MMP-9 mRNA showed no significant changes in its expression with all different levels of concentration, while MMP-9 protein showed 1.5 times increase with 10 ng/mL rHGF but 0.4 times decrease with 100 ng/mL. MMP-2 mRNA expression treated with recombinat HGF were increased 1.6 times with 24 hour culture and 2.3 times with 36 hour culture. MMP-2 protein showed 1.9 times increase only for the case of 24 hour culture. MMP-9 mRNA expression of recombinant HGF-treated groups was decreased 0.7 times compared with that of control group in 36 hours. MMP-9 protein expression were increased by 1.2, 1.6 and 1.9 times as culture time increase to 36, 48, and 72 hours accordingly, compared with that of normal control. CONCLUSION: This result suggests that the HGF might partially regulate the invasion of trophoblasts through MMP-2 and MMP-9.

Influence of Hepatocyte Growth Factor on its Receptor (c-met) expression and Invasion in HT Cell Line / 대한산부인과학회잡지

OBJECTIVE: To evaluate the invasive capacity of trophoblastic cells when treated with HGF, and see whether HGF induces c-met expression in vitro. METHODS: HT cell line was treated with recombinant HGF (rHGF) at different concentrations (0, 10, 50 and 100 ng/mL) and cultured for 24 hours. To evaluate according different time of culture, HT cell line was pre-treated with 50 ng/mL rHGF and cultured for 24, 36, 48 and 72 hours. We analyzed the expression of c-met mRNA using reverse transcriptase-polymerase chain reaction and the expression of c-met protein using western blot in each samples. We also observed cellular invasion capacity through the invasion assay under a microscope and confirmed 72 kDa gelatinase and 92 kDa gelatinase expression patterns by zymography assay. RESULTS: The expressions of c-met mRNA and protein were increased in all concentrations of rHGF, compared with that of normal control although it was not in dose-dependent fashion. In invasion assay, the number of invaded HT cells were increased in dose-dependent fashion, compared with that of normal control. In zymography ssay, the expression of 72 kDa gelatinase was increased in dose-dependent fashion, compared with the control. However, 92 kDa eglatinase was not detected in any studied group. CONCLUSION: These results suggests that HGF might be related to upregulation of trophoblast cell invasiveness by activation of c-met and subsequent induction of 72 kDa gelatinase.

Expression of insulin-like growth factorIGF-II and IGF binding proteinIGFBP-1 in preeclamptic placentas / 대한산부인과학회잡지

No abstract available.

Expression of Hepatocyte Growth Factor and its receptor in Placentas of Mild and Severe Preeclampsia / 대한산부인과학회잡지

No abstract available.

Influence of Hypoxic Condition on Invasion of Cultured Trophoblast / 대한주산의학회잡지

OBJECTIVE: To investigated whether lowering oxygen tension affects invasion of cultured trophoblast. METHODS: Trophoblasts were isolated from the normal placenta in early pregnancy(6-10 weeks in gestation). Isolated trophoblasts were cultured under normoxic(5% CO2, 95% humid air in incubator) and hypoxic(MERCK, 1% O2, 99% CO2) conditions for 24, 48 and 72 hours, respectively. The proliferation ability was measured using [H3] thymidine assay. Total RNA was extracted from the cultured trophoblasts. The expressions of matrix metalloproteinase(MMP-2) and tissue inhibitor of metallo- proteinase(TIMP-2) were determined by reverse transcription- polymerase chain reaction(RT-PCR) and Northern blot analysis. The invasiveness of cultured trophoblast was observed using in vitro invasion assay. RESULTS: [H] thymidine assay indicated that cellular DNA synthesis was not affected by the culture condition. The expression of MMP-2 mRNA was decreased at 24 hours and then progressively increased in the time-dependent manner in each culture condition. The expression of TIMP-2 was decreased in the time-dependent manner under hypoxic condition. In vitro invasion assay revealed that the cultured trophoblasts under hypoxic condition has more invasive ability than them under normoxic condition. CONCLUSION: These data suggests that hypoxic condition may stimulates the invasion of trophoblast in the human placentation. And MMP-2 and TIMP-2 may be related to control their invasiveness under hypoxic condition.

Gene Expression of Vascular Endothelial Growth Factor(VEGF) and Placental Growth Factor(PlGF) in Human Placenta / 대한산부인과학회잡지

OBJECTIVE: To determine whether gene expressions of VEGF and PlGF are different between the human placenta of normal and abnormal pregnancy. METHODS: Placenta was collected at each trimester of normal pregnancy, missed abortion, intrauterine growth retardation and pre-eclampsia. Total RNA was extracted from placenta. Reverse transcription-polymerase chain reaction(RT-PCR) was performed using VEGF and PlGF primer. RESULTS: VEGF121, VEGF165 and VEGF189 were identified in normal pregnancy and missed abortion. In two cases of four IUGR and one case of three pre-eclampsia, four of isoforms (VEGF121, VEGF145, VEGF165, and VEGF189) were identified. The intensity of signal was strongest for VEGF165 in all cases. PlGF131 and PlGF152 were identified in all cases. However, the signal intensities of VEGF121, VEGF165, VEGF189, PlGF131 and PlGF152 were not different according to the gestational age. They were also not different between normal pregnancy and abnormal pregnancy. CONCLUSION: VEGF and PlGF were not only expressed at placenta but also overexpressed in part of IUGR and pre-eclampsia. The results suggest that VEGF may play a role in the induction of angiogenesis of placenta in normal pregnancy and its production may be increased under the hypoxic condition.