Downregulation of notch signaling pathway in late preterm and term placentas from pregnancies complicated by preeclampsia.

Preeclampsia (PE) is a major cause of maternal mortality and morbidity, affecting 3-5% of all pregnancies. The Notch signaling pathway plays an important role during placental development, activating several target genes. Defects in the Notch pathway have adverse effect on placentation. The aim of this study was to investigate the expression of receptors NOTCH1,-2,-3,-4, ligands DLL1,-3,-4, JAG1,-2 and target genes HEY1,-2 in placental tissue samples from 20 late preterm or term pregnancies complicated by PE versus 20 normal pregnancies. mRNA levels of the studied molecules were measured by quantitative Real-Time PCR (qRT-PCR), while the protein expression of the intracellular domain of NOTCH2 (NICD2) and NOTCH3 (NICD3) was measured by Western Blot (WB). qRT-PCR analysis revealed that NOTCH1, NOTCH4 and DLL1 were not expressed in the placenta. On the contrary, NOTCH2, NOTCH3, DLL3, DLL4, JAG1, JAG2, HEY1 and HEY2 mRNA levels were downregulated in PE samples vs. controls (p<0.01). WB confirmed that NICD2 (p = 0.014) and NICD3 (p<0.001) protein levels were also lower in PE specimens. Statistical analysis revealed several significant associations: of NOTCH3 mRNA expression with smoking during pregnancy (p = 0.029), of NICD3 protein levels (p = 0.028) and DLL3 mRNA levels (p = 0.041) with birth weight centile, and of HEY2 transcript levels with parity (p = 0.034) and mode of delivery (p = 0.028). Our results suggest that Notch pathway downregulation is associated with PE. Further studies are required in order to determine the role of these molecules in PE pathogenesis and to evaluate their potential use for the early detection and treatment of PE

Subcutaneous Fat Necrosis and Hypercalcemia with Nephrocalcinosis in Infancy: Case Report and Review of the Literature

Subcutaneous fat necrosis is an uncommon benign panniculitis affecting more commonly full-term newborns. It has been associated with birth asphyxia and meconium aspiration, as well as therapeutic hypothermia. Although the prognosis is generally favorable, complications such as hypercalcemia, thrombocytopenia, hypoglycemia and hypertriglyceridemia may complicate its course. The most serious complication is hypercalcemia that may reach life threatening levels and can be associated with nephrocalcinosis. We thereby describe a case of subcutaneous fat necrosis after therapeutic hypothermia, which presented with late-onset refractory severe hypercalcemia and persistent nephrocalcinosis during the follow up of the patient. Due to the risk of the development of chronic kidney disease, we highlight the importance of careful monitoring of hypercalcemia and review the literature of subcutaneous fat necrosis related to nephrocalcinosis

Expression analysis of Notch signaling pathway between normal and PE placentas.

<p><b>P-value (c):</b> crude p-value; <b>P-value (a):</b> P-value adjusted for gestation period, mode of delivery and smoking during pregnancy. All values are presented as mean ± SEM.</p><p>Expression analysis of Notch signaling pathway between normal and PE placentas.</p

Notch signaling pathway pair-wise mRNA co-expression analysis in normal placentas.

<p><b>CC</b>: Correlation coefficient.</p><p>Notch signaling pathway pair-wise mRNA co-expression analysis in normal placentas.</p

Clinical characteristics of the study groups.

<p>^a Student’s T test</p><p>^b Mann-Whitney U test</p><p>^c Chi-square test</p><p>^d Fisher’s exact test</p><p>All tests were 2-tailed.</p><p>Clinical characteristics of the study groups.</p

Notch signaling pathway pair-wise mRNA co-expression analysis in preeclamptic placentas.

<p><b>CC</b>: Correlation coefficient.</p><p>Notch signaling pathway pair-wise mRNA co-expression analysis in preeclamptic placentas.</p

Primer sequences, annealing temperatures and amplicon sizes for the qRT-PCR analysis of the studied genes.

<p>Primer sequences, annealing temperatures and amplicon sizes for the qRT-PCR analysis of the studied genes.</p

Schematic representation of Notch pathway molecules mRNA expression profile in our series of preeclampsia-complicated late preterm and term placentas.

<p>Red: Downregulation; White: Normal expression; Sky Blue: Overexpression.</p

Schematic depiction of the studied Notch signaling pathway molecules in late preterm and term placentas.

<p>Schematic depiction of the studied Notch signaling pathway molecules in late preterm and term placentas.</p