Heat shock transcription factor 1 expression is spatially distributed and selectively down-regulated in the human placenta during labour

Abstract

s / Placenta 35 (2014) A1eA112 A72 Conclusion: Altogether these results are new evidence for potential programming of the antioxidant response in fetal endothelial cells from LGA fetuses from obese mothers. Founding: Fondecyt 1120928. P2.33-N. HEAT SHOCK TRANSCRIPTION FACTOR 1 EXPRESSION IS SPATIALLY DISTRIBUTED AND SELECTIVELY DOWN-REGULATED IN THE HUMAN PLACENTA DURING LABOUR Akrem Abdulsid, Fiona Lyall University of Glasgow, Medical Genetics Institution, Glasgow, UK Heat shock proteins can be induced in cells as a protective mechanism to cope with cellular stress. The activation of the heat shock response is mediated by a master regulator, heat shock transcription factor 1(HSF1). HSF1 regulates target genes by binding to conserved elements in their promoter regions. The HSF1 inactive form is part of a chaperone protein complex; stress stimuli causes HSF1 to be released from the complex and become active after several post-translational modifications. HSF1 expression was examined in placentas obtained from women who delivered by cesarean section and compared to the equivalent zone of placentas obtained from women who delivered vaginally. Samples were obtained from 12 sites within each placenta: 4 equally spaced apart pieces were sampled from the inner, middle and outer placental zones. HSF1 protein expressionwas investigated byWestern blotting and real time PCR. Two HSF1 bands were observed which, according to the data sheet represent the phosphorylated 80 kDa and non-phosphorylated 65 kDa forms. These were found in all samples. No difference in protein expression of either formwas found between the three zones of the non-labour group. There was a significant decrease in outer zones compared to the middle zone of the labour group of both forms (p1⁄40.04). At the inner and middle zones there was a highly significant decrease in HSF1 expression in the labour group when compared to the non-labour group for both the phosphorylated form (p1⁄40.02, p1⁄40.01) and the non-phosphorylated form (p1⁄40.04, p1⁄40.008). No spatial differences were found within placentas at the mRNA level in either labour or non-labour. Therewas, paradoxically, an increase in HSF1 mRNA in the labour group at the inner zone (p1⁄40.02). HSF1 is spatially controlled and its reduction may help promote, or be a consequence of the oxidative stress of labour. P2.34-N. PENA-SHOKEIR PHENOTYPE/FETAL AKINESIA DEFORMATION SEQUENCE: FROM PLACENTA TO SECONDARY MYOPATHY DehuaWang , Robert J. Hopkin , EmilyKing ,Maria A. Calvo-Garcia , Jerzy Stanek a Division of Pathology and LaboratoryMedicine, Cincinnati Children's Hospital, Cincinnati, Ohio, USA; Division of Medical Genetics, Cincinnati Children's Hospital, Cincinnati, Ohio, USA; Department of Radiology, Cincinnati Children's Hospital, Cincinnati, Ohio, USA Objectives: The etiologies of Pena-Shokeir phenotype (PSP), or fetal akinesia deformation sequence, include many genetic and acquired disorders, including the poor uteroplacental perfusion. Ă Methods: We report placental and autopsy results of a 33 weeks fetus with abnormal limb and body posturing and polyhydramnios revealed by ultrasound at 29 weeks gestational age, preceded by unremarkable ultrasounds at 20 weeks. Subsequent magnetic resonance imaging at 31weeks also showed several other structural anomalies. Amniocentesis showed a 46,XY karyotype. The fetus was spontaneously delivered after premature rupture of membranes and expired shortly afterwards. Results: The autopsy showed a normal size male fetus with pulmonary hypoplasia, limb and facial dysmorphism, arthrogryposis with pterygia, right thoracolumbar scoliosis and opisthotonus, eventration of right hemidiaphragm, extensive perisylvian and occipital lobe polymicrogyria, focal leptomeningeal neuroglial heterotopias, focal gliosis, meningeal and brain microcalcifications (pseudoTORCH pattern), and liver sinusoidal myelopoiesis, ductopenia, and prominent portal ductal plates. Marked variation in myofiber size with scattered small atrophic fibers and mild perimysial fibrosis were noted predominantly in the muscles of the elbow pterygia. SNP microarray analysis detected no clinically significant chromosomal imbalances. The umbilical cord was hypercoiled (coiling index 0.47 coils/cm). The placenta showed stage 3 acute chorioamnionitis and subchorial intervillositis, stem obliterative endarteritis and perivascular stem edema, multiple villous infarctions, laminar necrosis of placental membranes, intervillous thrombi, clusters of avascular terminal villi, villous hemosiderosis in a lobular distribution, and basal plate myometrial fibers. Conclusion: This case illustrates the predominantly placental cause of PSP which, in comparison to other reported cases, developed late in the 2nd trimester. The placenta featured the thrombotic-ischemic-inflammatory overlap pattern of injury that would explain the secondary brain and muscle lesions. This pathomechanism of PSP has not been reported so far. The acute placental hypoxic lesions were probably terminal events and were not operative in the pathogenesis of PSP. P2.35. DIABETES AFFECTS RAT PLACENTAL MORPHOLOGY AND PREGNANCY Priscilla Farias, Karine Souza, Emerson Fioretto, Marcio Santos, Marlucia Aires Federal University of Sergipe, Sao Cristovao, Sergipe, Brazil Objectives: In the Brazilian health public system, 7.6% of pregnant women older than 20 years are diabetic. Results from human and rodent diabetic experimental models have suggested that the placenta is a compromised target, which largely suffers the impact of maternal diabetes. This causes problems in maternal and fetal exchange, which increases abnormal fetal development and perinatal morbidity rates. In view of the importance of diabetes during pregnancy for maternal and neonatal health, the objective of the present study was to assess placental and fetal weight, and placental morphological changes in diabetic female rats using histological and stereological techniques. Methods: diabetes was induced by a single injection of alloxan in saline solution on gestational day (gd) 8 inWistar rats. On 17 gd, rats from control and diabetic groups were anesthetized, exsanguinated, and laparotomized to remove the uterine horns for weighing of fetuses and placentas. Placentas were sampled and processed for paraffin embedding, and histological and stereological analysis. Results: Placental weight was not different between the two groups at 17 gd. However, fetal weight was reduced in the diabetic group compared with control. The placentas from the diabetic group had an enlarged junctional zone, a straight arrangement of fetal capillaries and maternal sinusoids in the labyrinth zone and larger absolute volume. Spongiotrophoblast cells, glycogen cells, and labyrinth zone volume were expanded in diabetic female rats, while trophoblast giant cell volume was not different between the groups. Conclusion: This study shows the negative effect of severe hyperglycemia on placental and fetal development, as evidenced by reduced fetal weight, and altered placental morphology and volume.