Jenn-Jhy Tseng

Metastasis associated lung adenocarcinoma transcript 1 is up-regulated in placenta previa increta/ percreta and strongly associated with trophoblast-like cell invasion in vitro

Placenta previa increta/percreta (I/P) is a severe form of invasive placentation associated with massive peripartum hemorrhage, which often requires Cesarean hysterectomy. The pathogenesis of invasive placentation is multidimensional, involving decidual deficiency, endomyometrial damage and excessively deep trophoblast invasion into the uterus. In this study, annealing control primer-polymerase chain reaction (ACP-PCR) was used to identify differentially expressed genes, which may impair placentation resulting in placenta previa I/P. Placental tissues from I/P and non-increta/percreta (non-I/P) sites were concomitantly collected from patients undergoing Cesarean hysterectomy. After ACP-PCR experiments (three patients), the differentially expressed bands, consistently showing up- or down-regulated trends between each of the I/P and non-I/P tissue pairs, were cloned and sequenced. Human non-protein coding metastasis associated lung adenocarcinoma transcript 1 (MALAT-1) gene was identified. Real-time quantitative PCR (10 patients) confirmed significant overexpression of MALAT-1 in I/P samples (P = 0.005). To investigate the role of MALAT-1 gene in the regulation of trophoblast cell invasion, targeting of MALAT-1 mRNA expression with short interfering RNA (siRNA) in trophoblast-like BeWo, JAR and JEG-3 choriocarcinoma cells was performed. The invasion ability of these cells was significantly suppressed after siRNA silencing (P < 0.001), and this was not correlated with abnormal MMP-2 and MMP-9 enzyme activities. Our results suggest that MALAT-1 expression in placenta previa I/P is increased and its down-regulation inhibits trophoblast-like cell invasion in vitro. MALAT-1 might be involved in regulating trophoblast invasion during the development of advanced invasive placentation.

Detection of Chromosome Aberrations in the Second Trimester Using Genetic Amniocentesis: Experience during 1995-2004

OBJECTIVE To retrospectively investigate the 10-year experience of prenatal diagnosis of fetal chromosome aberrations by second-trimester amniocentesis. METHODS Data were collected at Taichung Veterans General Hospital between 1995 and 2004 from cytogenetic analyses of cultured amniocytes from second-trimester amniocentesis. The main indications for amniocentesis included advanced maternal age, abnormal maternal serum screening results, and abnormal ultrasound findings. Chromosome aberrations included autosomal aneuploidies, sex chromosome aneuploidies, polyploidies, and rearrangements. Variant chromosomes were considered to be normal and excluded. RESULTS A total of 7,028 amniocenteses were performed and analyzed for chromosome aberrations. Among these, 4,026 (57.29%) were for advanced maternal age, 1,500 (21.34%) for abnormal maternal serum screening results, 553 (7.87%) for abnormal ultrasound findings, and 949 (13.50%) for other reasons. The highest detection rate of chromosome aberrations was in cases undergoing amniocentesis for abnormal ultrasound findings (8.86%), followed by other reasons (2.74%), abnormal maternal serum screening results (2.60%), and advanced maternal age (2.31%). Chromosome aberrations were detected in 207 cases (2.90%), including fetuses of 93 older mothers, 39 mothers with abnormal serum screening results, 49 mothers with abnormal ultrasound findings, and 26 mothers with other reasons for amniocentesis. Of fetuses with chromosome aberrations, 144 (69.56%) had trisomy 13, trisomy 18, trisomy 21, or sex chromosome disorder. The other 63 cases (30.44%) included balanced translocation, unbalanced abnormality, inversion, and marker chromosome. CONCLUSION For daily practice, our data could offer a database for proper genetic counseling, such as termination issues and future pregnancies.

Differential Expression of Growth-, Angiogenesis- and Invasion-Related Factors in The Development of Placenta Accreta

Placenta accreta is the major cause of maternal death complicated by massive peripartum hemorrhage. Its development is traditionally considered to be related to a decidual defect caused by previous cesarean deliveries or uterine curettages. Usually, placental villi firmly adhere to the superficial myometrium and deeply invade, or even penetrate, the uterine wall. Abnormal uteroplacental neovascularization is another characteristic. Therefore, we hypothesized that placenta accreta develops as a result of abnormal expressions of growth-, angiogenesis- and invasion-related factors in trophoblast populations. We have found, in pregnancies complicated by placenta accreta: upregulated epidermal growth factor receptor and downregulated c-erbB-2 oncoprotein in syncytiotrophoblasts; downregulated vasculoendothelial growth factor receptor-2 expression in syncytiotrophoblasts and increased vasculoendothelial growth factor in placental lysates; and downregulated Tie-2 expression in syncytiotrophoblasts and enhanced angiopoietin-2 level in placental lysates. However, matrix metalloproteinase expression was not upregulated, so the association of these invasion-related molecules with placenta accreta is less likely. Taken together, these findings imply that complex factors, either alone or in combination, might be responsible for the development of placenta accreta. Further studies are needed to understand the signaling pathways and possible genetic events.

Fetal echocardiographic diagnosis of isolated ductus arteriosus aneurysm: a longitudinal study from 32 weeks of gestation to term

To investigate the echocardiographic characteristics of isolated fetal ductus arteriosus aneurysm (DAA) and the factors influencing its development.

Prenatal Diagnosis of Isolated Fetal Hydrocolpos Secondary to Congenital Imperforate Hymen

A 32-year-old primigravida was referred to our hospital at 36 weeks of gestation with a fetal pelvic mass. Ultrasonography showed the fluid-filled area to be a 9 x 4 x 5-cm pear-shaped retrovesical mass with a funnel-shaped blind pouch at the distal end of the fetal vagina. Marked left hydronephrosis resulting from mass compression was also detected. Fetal magnetic resonance imaging further defined a pelvic lesion extending cephalically into the abdomen and caudally into the vagina. Membranal protrusion of the introitus was clearly identified. Therefore, the diagnosis of congenital imperforate hymen with hydrocolpos was established. At 38 weeks of gestation, a 2,966-g female infant was delivered vaginally with good Apgar scores. Physical examination of the neonate revealed a bulging membrane covering the vaginal opening. The presence of syndromic disorders (McKusick-Kaufman, Ellis-van Creveld or Bardet-Biedl syndromes), genitourinary and anorectal anomalies were excluded. The karyotype was 46,XX. A hymenotomy was performed on the second day of life. The infant recovered fully after hymenotomy.

IMP1 promotes choriocarcinoma cell migration and invasion through the novel effectors RSK2 and PPME1

OBJECTIVE Oncofetal protein insulin-like growth factor II mRNA-binding protein 1 (IMP1) regulates cellular proliferation and migration. Expression of IMP1 is limited to a few adult human tissues. However, it commonly expresses in a variety of cancers. Our objective was to study the regulatory mechanism of IMP1 on the cellular functions of choriocarcinoma (CC) JAR cells. METHODS IMP1 protein levels were measured in CC tissues via immunohistochemistry. Specific siRNAs were used to down-regulate gene expressions. The abilities of migration and invasion were estimated by wound-healing and Matrigel chamber assays. The profile of IMP1-binding genes was investigated with an Agilent microarray. RT-qPCR, RNA immunoprecipitation, and IMP1 rescue experiments were performed to confirm the association between IMP1 and its binding genes. Gene expression was further analyzed by using RT-PCR and Western blotting. RESULTS Strong IMP1 expressions were frequently detected in CC tissues. Knockdown of IMP1 expression in JAR cells inhibited cell migration and invasion, but did not affect cellular proliferation and morphology. Microarray and RNA-immunoprecipitation results revealed several candidate genes regulated by IMP1. Among them, ribosomal protein S6 kinase (RSK2) and protein phosphatase methylesterase 1 (PPME1) were confirmed to be down-regulated in IMP1-depleted JAR cells. Re-expression of IMP1 into the cells restored the expressions of RSK2 and PPME1. Furthermore, the depletion of RSK2 or PPME1 decreased the migration and invasion of JAR cells. CONCLUSION Our results suggest that IMP1 plays an essential role in the regulation of migration and invasion of human CC cells, possibly through the novel effectors RSK2 and PPME1.

Elevated amniotic fluid stromal cell-derived factor-1α (SDF-1α) concentration in mid-gestation as a predictor of adverse birth outcomes.

Background: This study aimed to predict maternal and neonatal outcomes by measuring mid‐trimester amniotic fluid stromal cell‐derived factor‐1α (SDF‐1α) concentration in healthy women. Methods: Mid‐trimester amniotic fluid samples from healthy women with a singleton pregnancy were obtained at the time of genetic amniocenteses. SDF‐1α concentrations were determined by enzyme‐linked immunosorbent assay. Maternal and neonatal characteristics were recorded. Results: A total of 210 samples were collected. According to the SDF‐1α cutoff value established by the receiver operating characteristic curve analysis (< 6.42 vs. ≥ 6.42 pg/mL), there was a trend toward higher preterm birth rate, lower birth weight and lower 1‐minute and 5‐minute Apgar scores when SDF‐1α levels increased (p < 0.05). The pair comparison between normal and selected pregnancy disorders (gestational diabetes, pre‐eclampsia, and abnormal placentation) showed no statistical significance (p > 0.05). Pearsons correlations of SDF‐1α to gestational age at delivery (r = −0.151) and birth weight (r = −0.194) were significant (p < 0.05). In the multivariate analysis on mid‐trimester SDF‐1α levels, maternal age at sampling (regression coefficient = −0.163) and 1‐minute Apgar score (< 7 vs. ≥ 7, regression coefficient = 2.028) were both significant (p < 0.05). Conclusion: Increased SDF‐1α levels in mid‐trimester amniotic fluid suggest a possible role in predicting pregnant women at risk of adverse neonatal outcomes including higher preterm birth rate, lower birth weight, and lower Apgar scores.

TUBOOVARIAN ABSCESS IN PREGNANCY

Cervical mucus plug and intact amniotic membrane protect against ascending infection; therefore, tuboovarian abscess (TOA) during pregnancy is an extremely rare condition. This condition not only increases maternal morbidity and mortality, but also increases the risk of fetal jeopardy [1]. Proposed pathogeneses of TOA during pregnancy are variable and include hematogenous spreading, lymphatic spreading from contiguous organ, infection in a previously existing ovarian cyst, and flare-up of an old infection [2]. In recent reports, ascending infection caused by gonococci attached to motile spermatozoa, the use of assisted reproductive technology, and structural uterine abnormalities suggested other possible causes of the formation of TOA during the gestational period [3–5]. A 35-year-old woman, gravida 2, para 0, came to our emergency room at 29 weeks’ gestation with the chief complaint of flank pain and intermittent lower abdominal pain for 3 days. Fever (temperature up to 38°C) was also noted for 1 day. She denied any history of systemic diseases. Her previous pregnant history was significant owing to preterm premature rupture of membranes with oligohydramnios at 16 weeks’ gestation, and the pregnancy was terminated because of poor prognosis. During the present pregnancy, she received regular antenatal care at our hospital. Group B Streptococcus infection was noted at 25 weeks’ gestation, with the patient complaining of copious leukorrhea. A 2-week course of antibiotics was prescribed according to the sensitivity test. With problems of bilateral flank soreness and intermittent lower abdominal pain, she first visited a local clinic for help, where tocolytic agents were prescribed to control uterine contractions. However, fever with leukocytosis (white blood cell count, 14,000/mm 3 ) and bacteriuria occurred in the follow

Prenatal Diagnosis of Extrastructurally Abnormal Chromosomes: Clinical Experience and Literature Review

Background: To evaluate the clinical association of extrastructurally abnormal chromosomes (ESACs) with pregnancy outcome based on the cytogenetic characteristics of the ESACs. Methods: We retrospectively reviewed 12 ESAC cases identified from 12,991 cases who received genetic amniocentesis between January 1983 and March 2008. Prenatal ultrasound findings, characteristics of ESACs (karyotypes, special features, origin, inheritance) and pregnancy outcomes were recorded. Results: The prenatal prevalence of ESACs was 0.092% (12/12,991). Of the 12 ESAC cases, all were de novo. Seven (58.3%) originated from nonacrocentric chromosomes and the other 5 (41.7%) were from acrocentric chromosomes, with 3 originating from chromosome 15. Six of the 12 cases (50%) were large ESACs; however, the other 6 (50%) were medium to small ESACs. All acrocentric ESACs contained dicentric and bisatellite characteristics. Using FISH and SKY techniques, the origins of 2 cases (patients 10 and 12) were clearly identified to be from chromosomes 15 and 10, respectively. Five of the 12 ESAC cases (41.7%) had congenital anomalies found by prenatal ultrasound. All were nonacrocentric in origin that were medium (1/5) to large (4/5) in size. After prenatal genetic counseling, 8 of the 12 (66.7%) couples opted to terminate the pregnancy. The other 4 (33.3%) continued the pregnancy and their babies were delivered at term normally and were followed‐up, with normal development ranging from 2 to 17 years. Conclusion: With sophisticated cytogenetic characterization and ultrasound examination, it is possible to precisely categorize most fetuses with ESACs as being either at high risk of abnormality or at a relatively low risk.

CARDIOTOCOGRAPHIC AND DOPPLER ULTRASONOGRAPHIC FINDINGS IN A FETUS WITH BRAIN DEATH SYNDROME

OBJECTIVE The diagnosis of brain death syndrome by cardiotocography (CTG) and Doppler ultrasonography (US) is reported in a fetus at 35 weeks of gestation. CASE REPORT A 23-year-old, gravida 2, para 0, woman was referred to our hospital because of the absence of fetal movements. CTG showed fixed fetal heart rate (FHR) pattern. A detailed Doppler US examination of the fetus showed extensive cystic lesions of both cerebral hemispheres, polyhydramnios, total absence of neuromuscular parameters of biophysical profile (BPP) and the cessation of cerebral blood flow. Umbilical cord artery blood gas analysis showed pH 7.3, PaO2 30 mmHg and PaCO2 35 mmHg. A floppy male infant weighing 2,450 g was delivered vaginally at 36 weeks of gestation and the Apgar scores were 1 and 1 at 5 and 10 minutes, respectively. The neonate died 2 days after delivery. Postmortem examination of the brain showed diffuse, anoxic changes with multicystic encephalomalacia in both hemispheres and the brain stem. No other maternal or placental abnormalities were seen. CONCLUSION The possibility of intrauterine brain death should be considered in all cases of prolonged fixed FHR pattern, accompanied by absence of neuromuscular parameters of BPP, polyhydramnios and demonstrated cessation of cerebral blood flow by Doppler US. Increased awareness of this event may prevent unnecessary emergency cesarean section.