Alterations In Placental Expression Research Articles

Alterations in Placental Inflammation-Related Gene Expression Partially Mediate the Effects of Prenatal Alcohol Consumption on Maternal Iron Homeostasis.

Prenatal alcohol exposure (PAE) is associated with alterations in maternal and infant iron homeostasis that are consistent with changes seen in the setting of inflammation. We hypothesized that PAE leads to alterations in the placental expression of genes related to iron metabolism and inflammation that play functional roles in the teratogenic effects of alcohol on iron homeostasis. A total of 126 heavy-drinking women (≥1 oz (30 mL) absolute alcohol/day (~1.67 standard drinks/day) or women reporting binge drinking (≥2 drinks/occasion)) and 80 control women (<0.5 oz AA per day, no binging) in Cape Town, South Africa were interviewed prenatally regarding demographics, and alcohol, smoking, and drug use around conception and during pregnancy. Prenatal/maternal and infant hemoglobin and ferritin were measured. Whole-transcriptome RNA sequencing analysis was performed on flash-frozen transplacental tissue samples. Gene sets related to iron metabolism (n = 398) and inflammation (n = 467) were constructed by searching the Molecular Signatures Database for related ontology terms. Principal component analysis (PCA) yielded 59 factors for each theme. In multivariable regression models, PAE was related to 2 iron metabolism PCA factors (PCs) and 5 inflammation PCs, among which 2 iron metabolism and 4 inflammation factors were related to at least 1 key maternal or infant iron outcome. In causal inference analyses based on marginal structural models and the product method, the alterations in the expression profile of genes with functions in immune cell regulation, cytokine activity, angiogenesis, hematopoiesis, and ubiquitous cell processes appeared to partially mediate the relation of prenatal drinking frequency (days/week) around conception to a lower maternal hemoglobin-to-log(ferritin) ratio (proportion mediation = 51.35%). These findings suggest that placental inflammation may be partly responsible for the differences in alcohol-related iron homeostasis patterns between pregnant and non-pregnant adults.

P13. Alterations in placental expression of Caveolin-1, Cavin-1 and eNOS in women with pre-eclampsia

P13. Alterations in placental expression of Caveolin-1, Cavin-1 and eNOS in women with pre-eclampsia

Placental Dysferlin Expression is Reduced in Severe Preeclampsia

Dysferlin (DYSF) and myoferlin (MYOF), members of the ferlin family of membrane proteins, are co-expressed in human placental syncytiotrophoblast (STB). Although the role of these ferlin proteins in the placenta has yet to be established, it has been suggested that DYSF and MYOF may contribute to the stability of the apical STB plasma membrane. The release of STB-derived cellular debris increases in the setting of preeclampsia (PE), suggesting relative destabilization of the hemochorial interface. To test whether PE was associated with alterations in placental expression of DYSF and/or MYOF, a cross-sectional study was performed using specimens of villous placenta collected form women with severe PE ( n = 10) and normotensive controls ( n = 10). DYSF and MYOF expression were examined using quantitative real–time RT-PCR, immunoblotting, and immunofluorescence labeling of tissue specimens. Placental DYSF expression was 57% lower at the mRNA level ( p = 0.03) and 38% lower at the protein level ( p = 0.026) in severe PE as compared to normotensive subjects. There were no differences in placental MYOF protein or mRNA expression between these groups. No appreciable changes in the distribution of DYSF or MYOF within placental villi was observed in PE relative to control specimens. We conclude that DYSF expression is reduced in severe PE relative to gestational age-matched controls. As DYSF has a role in membrane repair, these data suggest a role for DYSF in the stability of the apical STB plasma membrane and may account, at least in part, for the increased shedding of microparticles from this membrane in PE.

Changes in Placental Dipeptidyl Peptidase IV in Preeclampsia with Intrauterine Growth Restriction

The purpose of this study was to examine alterations in placental expression of dipeptidyl peptidase IV (DPPIV). The localization of DPPIV was compared in control and preeclamptic placentas. Enzyme activity, mRNA, and protein expression were also measured. In term placentas, DPPIV was expressed preferentially in the fetal vascular endothelial cells within stem villi and only weakly in the villous stromal cells. DPPIV activity in control placentas showed no remarkable changes throughout gestation. Levels of activity in samples from normotensive control cases and women having preeclampsia with or without intrauterine growth restriction were 11.8 +/- 2.1, 13.4 +/- 1.1, and 15.3 +/- 0.62 pmol pNA/min/mg protein, respectively. The preeclamptic placentas with intrauterine growth restriction thus showed significantly higher levels of activity than the controls (p < 0.05). We propose that placental DPPIV influences fetal metabolism via the degradation of fetoplacental circulating bioactive peptides, including incretins, resulting in the regulation of fetal growth.