The effect of granulocyte-macrophage-stimulating factor on the gene expression in human trophoblast of early pregnancy / 대한산부인과학회지

OBJECTIVE: Granulocyte-macrophage colony-stimulating factor (GM-CSF) facilitates mammalian embryonic development and implantation. However, its biological function after implantation is not elucidated. The aim of this study is to assess the changes of gene expression by GM-CSF in human trophoblast obtained in early pregnancy. METHODS: Human trophoblast obtained in early pregnancy was cultured with or without GM-CSF. The difference of gene expression was evaluated with microarray and selected genes were reevaluated with real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Microarray analysis revealed that the expressions of 468 genes were increased while those of 40 genes were decreased by GM-CSF. These genes were evaluated according to the known biologic pathways. The regulation of actin cytoskeleton and focal adhesion pathways were mostly influenced by GM-CSF. Annexin A2, thymosin-like 3, vimentin, myogenin, ACK1, and tensin1 genes were selected for real-time RT-PCR. The increased expressions of of vimentin and ACK1, and decreased expressions of tensin1 were confirmed by real-time RT-PCR. CONCLUSION: GM-CSF activates focal adhesion pathway in human trophoblast by increasing the expression of vimentin and ACK1, and decreasing the expression of tensin1.

The effect of GM-CSF on the expression of implantation-related genes in mouse embryo / 대한산부인과학회지

OBJECTIVE: GM-CSF is produced in female reproductive tract and may play an important role in the process of implantation. Body of evidence suggests that GM-CSF could improve pregnancy rate in many species of mammals when it was added in culture media. The aim of this study is to assess how GM-CSF affects the expression of implantation-related genes in mouse embryo. METHODS: Two hundred mouse embryos were divided into control and GM-CSF treated groups. The embryos were treated with or without 10 ng/ml of GM-CSF for 72 hours. Total RNA was isolated and compared with oligo microarray. The implantation-related genes influenced by GM-CSF were repeatedly analyzed by real-time PCR. RESULTS: After oligo microarray, 64 genes were increased and 35 genes were decreased by GM-CSF. Among those genes, MMP2, FABP3, Dppa5 and TAS1 were selected for real-time PCR analysis. Four integrins and FAK were also selected. We confirmed the increase of MMP2 and FABP3 by GM-CSF with real-time RT-PCR (1.687 and 1.580 fold, respectively). Other genes were found to be minimally increased. CONCLUSION: GM-CSF induces the increased expression of MMP2 mRNA in mouse embryo, and then increases the invasiveness of the trophoblast. The role of FABP3 in the process of implantation remained to be elucidated.

The Modulation of IL-12 by Phosphodiesterase IV Inhibitor and Subsequent Changes of Th-1, Th-2 Cytokines in Human Endometrial Tissue / 대한산부인과학회잡지

OBJECTIVE: To assess the capability of phosphodiesterase type IV inhibitor (rolipram) to suppress IL-12 in human decidua and the subsequent changes of Th-2 cytokine (IL-10) and Th-1 cytokine (TNF-alpha). METHODS: Decidual tissues of 10 first-trimester pregnant women and 10 first-trimester pregnant women diagnosed as missed abortion were collected by dilatation and currettage. The decidual tissues were treated with rolipram for 6 hours. Protein and mRNA expression in the tissues were analysed by western blotting, immunohistochemistry and reverse transcription-polymerase chain reaction. RESULTS: Rolipram, in the concentration above 1 microgram/ml, could decrease the expression of IL-12p35 (control: 46.37+/-7.38, rolipram: 24.34+/-8.46) and IL-12p40 mRNA (control: 31.7+/-5.8, rolipram: 14.9+/-4.6) and protein (control: 52.4+/-8.9, rolipram: 40.9+/-12.1). However, the expression of IL-10 and TNF-alpha mRNA and protein did not changed by rolipram. There was no difference in the cytokine expression pattern between the decidual tissues of normal pregnancy and missed abortion. CONCLUSION: Rolipram, the phosphodiesterase type IV inhibitor, could induce the decrease of IL-12 in human decidua. In human decidual tissue, unlike other human tissues, the decrease of IL-12 by rolipram did not modulate other Th-1/Th-2 cytokines. Inability of IL-12 to modulate other Th-1/Th-2 cytokines might be related with unique cytokine network in human decidua rather than its small extent of decrease.

Insulin-like Growth Factor-Binding Protein-1 in Cervical Secretion as a Predictor of Preterm Delivery / 대한산부인과학회잡지

OBJECTIVE: The phosphorylated isoforms of insulin-like growth factor-binding protein-1 (IGFBP-1) were produced by the decidua. The aim of this study was to evaluate whether the presence of phosphorylated IGFBP-1 (phIGFBP-1) in cervical secretions of pregnant women with preterm uterine contractions can predict an increased risk of preterm delivery and infectious complications. METHOD: The prospective study of 32 pregnant women who admitted under the diagnosis of preterm labor with intact membrane at gestational age of 24+0 to 36+0 weeks. Phsphorylated IGFBP-1 was qualitatively assayed using immunochromatography in cervical swab samples at the time of admission. The interval between the test and delivery, gestational age, duration of tocolysis, birth weight, CRP, ESR and the presence of neonatal infection were compared between positive and negative groups. RESULTS: There was no differnce in age, obstetric histories and gestational age and Bishop score at the time of admission between two groups. Eight pregnacies out of 13 positive group and two pregnacies out of 19 negative group resulted in preterm birth. The sensitivity and specificity of the phIGFBP-1 test to predict preterm birth were 80.0% and 77.3%, respectively. The mean getational age and interval between the test and delivery were 38.36 weeks and 45.0 days and 35.78 weeks and 35.46 days in negative and positive group respectively. The birth weight of the babies was significantly higher in negative group. The duration of tocolysis was longer in positive group with marginal statistical significance. The CRP, ESR and WBC count were not different. One postpartum sepsis, one neonatal death and one necrotizing enterocolitis were complicated in positive group. CONCLUSION: The presence of phIGFBP-1 is an usful marker to predict preterm birth in case of regular uterine contraction with intact fetal membranes.

Insulin-like Growth Factor-Binding Protein-1 in Cervical Secretion as a Predictor of Preterm Delivery / 대한산부인과학회잡지

OBJECTIVE: The phosphorylated isoforms of insulin-like growth factor-binding protein-1 (IGFBP-1) were produced by the decidua. The aim of this study was to evaluate whether the presence of phosphorylated IGFBP-1 (phIGFBP-1) in cervical secretions of pregnant women with preterm uterine contractions can predict an increased risk of preterm delivery and infectious complications. METHOD: The prospective study of 32 pregnant women who admitted under the diagnosis of preterm labor with intact membrane at gestational age of 24+0 to 36+0 weeks. Phsphorylated IGFBP-1 was qualitatively assayed using immunochromatography in cervical swab samples at the time of admission. The interval between the test and delivery, gestational age, duration of tocolysis, birth weight, CRP, ESR and the presence of neonatal infection were compared between positive and negative groups. RESULTS: There was no differnce in age, obstetric histories and gestational age and Bishop score at the time of admission between two groups. Eight pregnacies out of 13 positive group and two pregnacies out of 19 negative group resulted in preterm birth. The sensitivity and specificity of the phIGFBP-1 test to predict preterm birth were 80.0% and 77.3%, respectively. The mean getational age and interval between the test and delivery were 38.36 weeks and 45.0 days and 35.78 weeks and 35.46 days in negative and positive group respectively. The birth weight of the babies was significantly higher in negative group. The duration of tocolysis was longer in positive group with marginal statistical significance. The CRP, ESR and WBC count were not different. One postpartum sepsis, one neonatal death and one necrotizing enterocolitis were complicated in positive group. CONCLUSION: The presence of phIGFBP-1 is an usful marker to predict preterm birth in case of regular uterine contraction with intact fetal membranes.

A Clinical and Pathological Study of Dysfunctional Uterine Bleeding / 대한산부인과학회잡지

OBJECTIVES: Dysfunctional uterine bleeding(DUB) is defined as abnormal bleeding from the uterine endometrium unrelated to anatomic lesions of the uterus, and its incidence is 10-15% among gynecologic diseases. We conducted this study for understanding correlation between clinical aspecets and pathological findings of DUB. Methods: We conducted a retrospective review of 599 women with DUB who underwent endometrial biopsy with special regard to the relation between pathologic findings and presenting symtoms or complaints from Jan. 1988 to Dec. 1997. RESULTS: Age distribution of DUB was mainly 5th decade, mean age was 44.1years, among various bleeding patterns, intermenstrual bleeding was the most common pattern(31.6%) and the next was menorrhagia(25.0%). Histologic findings of endometrium were proliferative phase, 327 cases(54.6%), hyperplasia, 139 cases(23.2%), secretory phase, 74 cases(12.4%) in order of frequency, and there was no difference in distribution of histologic findings among various bleeding patterns. CONCLUSION: Compared to other previoius studies, our study showed more incidence of endometrial hyperplasia, especially at age group of 40 or more. So patients aged more than this age with abnormal uterine bleeding must undergo emdometrial biopsy for pathologic diagnosis. Patients who are diagnosed endometrial hyperplasia must be carefully followed up because there are possibilities of progression to endometrial carcinoma.

Clinical analysis of triple marker screening test for fetal Down syndrome in midtrimester of pregnancy-Low sensitivity of triple marker screening test / 대한산부인과학회잡지

OBJECTIVE: To assess the reliability of triple marker screening test in midtrimester pregnancy for fetal Down syndrome. METHODS: From October 1, 1996 to May 31, 1998 at Nowon Eulji Hospital, 3700 Pregnant women underwent serum tiple marker screening for Down syndrome during 15-20weeks of gestational age. The results of serum triple marker screenig tests for Down syndrome and the outcomes of pregnancies were retrospectively assesed. RESULTS: Sixty seven of 3700 cases(1.81%) were positive in screening test, and 3633(98.18%) cases were negative. Among 67 cases of positive screening test, 1 case(1.49%) was diagnosed as Down syndrome. Among 3633 cases of negative screening test, 4 cases(0.1%) were diagnosed as chromosomal abnormalies postnatally. Two of these 4 cases of chromosomal abnormalies were Down syndrome. CONCLUSION: With this results, sensitivity of triple marker screeing test for Down syndrome is very low as 33.3%. In order to increase the sensitivity, some compensatory adjustment is required in triple marker screening test.