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4 mM). RESULTS We found that palmitate alone induced the activation of the nucleotide-binding oligomerization domain-like receptor (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome in placental macrophages, which was associated with increased interleukin 1 beta release and an increase in apoptotic cell death. Glucose and insulin neither provoked these effects nor augmented the impact of palmitate itself. DISCUSSION Our findings confirm an impact of saturated fat on placental macrophage immune activation and could be relevant to the impact of metabolic stress in vivo. The umbilical cord (UC) connects the fetal blood supply to the placenta, so is exposed to all systemic endo- and xenobiotics. We have extensive experience using UC as an analytical matrix for detecting and/or quantitating drugs, chemicals and endogenous compounds. This technical note describes advantages (large amount available, ease of collection, small sample needed for use, rapid availability) and challenges (clinical relationships, processing difficulties, matrix effects on analytes and detection technologies) of UC as an analytical matrix in ELISA and LC/MS platforms, and provides guidance for successfully working with this tissue. INTRODUCTION Isolated term oligohydramnios (ITO) is an obstetrical complication of which the etiology, management, and clinical importance are controversial. In attempt to deepen our understanding, we aimed to study placental pathology and pregnancy outcomes in pregnancies complicated by ITO. MATERIALS AND METHODS – Maternal demographics, neonatal outcomes, and placental histopathology reports of all pregnancies complicated by ITO at 370/7 to 410/7 weeks were reviewed. Excluded were cases complicated by hypertensive disorders, intrauterine fetal growth restriction, placental abruption, and deliveries of undiagnosed small for gestational age neonates. Results were compared between the ITO group and a control group matched for gestational age and mode of delivery. Placental lesions were classified according to the current “Amsterdam” criteria. Composite adverse neonatal outcome was defined as one or more of the following early complications neonatal intensive care unit admission, sepsis, blood transfusion, phototherapy, respiratory morbidity, cerebral morbidity, necrotizing enterocolitis, or death. RESULTS The study group included 108 patients with ITO that were compared to matched controls. Placentas from the ITO group were characterized by higher rates of placental weights less then 10th centile (p  less then  0.001), abnormal cord insertion (p  less then  0.001), and maternal vascular malperfusion (MVM) lesions (p  less then  0.001). Neonates from the ITO group had lower birth weights (p  less then  0.002), and worse composite adverse neonatal outcome (p = 0.028) compared to controls. CONCLUSION – The current study demonstrates higher rates of placental MVM lesions, and worse neonatal outcome in pregnancies complicated by ITO. These novel findings suggest that ITO should be seen as part of the “placental insufficiency” spectrum. INTRODUCTION Dysregulation of placental apoptosis and autophagy are observed in pregnancy complications including preeclampsia and fetal growth restriction. However, studies of their changes in the placentas of women with gestational diabetes mellitus (GDM) show inconsistent results. We aimed to compare the changes in apoptosis, autophagy, and Bcl-2 family proteins in the placentas from women with normal pregnancies and those with GDM, with or without large-for-gestational age (LGA) infants and to investigate the effect of hyperglycemia on the changes in apoptosis, autophagy, and Bcl-2 family proteins in primary cytotrophoblastic cells. METHODS Villous tissues were obtained from normal pregnant women and those with GDM, with or without LGA infants. Primary cytotrophoblast cells were isolated from normal term placentas and cultured under standard, hyperglycemic, or hyperosmotic conditions. RESULTS Compared to placentas from normal pregnant women, those from GDM women with LGA infants were heavier, had lower beclin-1 and DRAM levels, less M30 and cleaved PARP immunoreactivity, and increased Ki-67 immunoreactivity. These changes were associated with increased Bcl-xL and decreased Bak levels. Increased glucose concentration led to lower ATG5, beclin-1, LC3B-II, p62, and DRAM levels, lower annexin V and M30-positive cell percentages, and less cleaved PARP changes compared with standard culture conditions. Hyperglycemia caused higher Bcl-xL levels and lower Bak and Bad levels than did standard culture conditions. DISCUSSION There were differential changes in apoptosis and autophagy between placentas from normal pregnant women and those from GDM women with LGA infants. Bcl-2 family proteins are likely involved in the regulation of these changes. INTRODUCTION Studies have reported that villous cytotrophoblasts (CTBs) undergo a partial epithelial to mesenchymal transition (EMT) when differentiating into extravillous cytotrophoblasts (EVTs). Selleckchem CBL0137 Epithelial splicing-regulatory protein 1 (ESRP1), an alternative splicing regulator, has been demonstrated to play important roles in the EMT process. Nevertheless, the roles of ESRP1 in the placentation remain undefined. METHODS ESRP1 expression in placental tissues throughout pregnancy was determined by immunohistochemistry and western blotting. The effect of ESRP1 knockdown by using small-interfering RNAs (siRNAs) on the phenotype of trophoblast cell line (HTR-8/SVneo) and villous explants was evaluated. RESULTS ESRP1 was localized within the CTBs, trophoblast columns, and EVTs located in the decidua. ESRP1 expression was changed during pregnancy, with the highest expression level in term placentae. ESRP1 knockdown significantly increased the migration and invasion of HTR-8/SVneo cells, as well as the outgrowth of EVTs from villous explants, without affecting cell proliferation. This enhanced effect was associated with the increased expression of N-cadherin, vimentin and CD44. DISCUSSION Our results suggested an important role for ESRP1 in regulating trophoblast migration and invasion during placentation.